Download A Guide For Patients, Survivors, And Loved Ones

Understanding
Non-Hodgkin Lymphoma
A Guide For Patients, Survivors, and Loved Ones
Fourth Edition
This guide is an educational resource compiled by the Lymphoma
Research Foundation (LRF) that provides general information on adult
non-Hodgkin lymphoma. Publication of this information is not intended
to take the place of medical care or the advice of a patient’s doctor.
Patients are strongly encouraged to talk to their doctors for complete
information on how their disease should be diagnosed, treated,
and followed. Before starting treatment, patients should discuss the
potential benefits and side effects of cancer therapy.
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www.lymphoma.org
Email:
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This patient guide is supported through unrestricted educational grants from:
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Turning Insights into Hope
© 2012 Lymphoma Research Foundation.
Information contained herein is the property of the Lymphoma Research Foundation (LRF).
Any portion may be reprinted or reproduced provided that LRF is acknowledged to be the source.
ACKNOWLEDGMENTS
The Lymphoma Research Foundation wishes to acknowledge those
individuals listed below who have given generously of their time and
expertise. We thank them for their contributions, editorial wisdom,
and advice, which have truly enhanced this publication. The review
committee guided the content and development of this publication.
Without their dedication and efforts, this publication would not have
been possible. We hope those in the lymphoma community will now
be better informed and have a better understanding of their illness
because of the gracious efforts of those involved in the planning and
execution of this comprehensive disease guide.
Review Committee
Bruce D. Cheson, MD, Georgetown University Hospital, Lombardi
Comprehensive Cancer Center
Morton Coleman, MD, Weill Cornell Medical College-NewYork
Presbyterian Hospital
Christopher R. Flowers, MD, Emory University School of
Medicine
Randy Gascoyne, MD, FRCPC, British Columbia Cancer Agency
Stephanie A. Gregory, MD, Rush University Medical Center/
Rush University
John P. Leonard, MD, Weill Cornell Medical College–NewYork
Presbyterian Hospital
Oliver W. Press, MD, PhD, Fred Hutchinson Cancer Research
Center, University of Washington
Sonali Smith, MD, The University of Chicago
Steven P. Treon, MD, PhD, Harvard Medical School
Julie M. Vose, MD, MBA, University of Nebraska Medical Center
Michael E. Williams, MD, University of Virginia School of
Medicine
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Understanding Non-Hodgkin Lymphoma
TA B L E O F C O N T E N T S
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Part 1 — Learning the Basics. . . . . . . . . . . . . . . . . . . . . . . . . 2
Chapter 1: Understanding Non-Hodgkin Lymphoma. . . . . . . . 2
Chapter 2: Seeking Medical Help . . . . . . . . . . . . . . . . . . . . . . . 17
Chapter 3: Getting a Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . 20
Chapter 4: Work-up Before Treatment Can Begin . . . . . . . . . 28
Part 2 — Treatment of Non-Hodgkin Lymphoma . . . . . 36
Chapter 5: What You Should Know
Before Starting Treatment . . . . . . . . . . . . . . . . . . . 36
Chapter 6: Treatments for Non-Hodgkin Lymphoma . . . . . . . 47
Part 3 — Side Effects and Living With Cancer . . . . . . . 69
Chapter 7: Common Treatment Side Effects . . . . . . . . . . . . . 69
Chapter 8: Managing Your Life During
and After Treatment . . . . . . . . . . . . . . . . . . . . . . . . 86
Part 4 — Clinical Trials and Advances in Treatment . . 91
Chapter 9: Overview of Clinical Trials . . . . . . . . . . . . . . . . . . . 91
Chapter 10: Advances in Treatment of Patients
With Non-Hodgkin Lymphoma . . . . . . . . . . . . . . 96
About the Lymphoma Research Foundation . . . . . . . . . . . . . . . . . . . 99
Understanding Non-Hodgkin Lymphoma
iii
INTRODUCTION
The purpose of this booklet is to help patients with non-Hodgkin
lymphoma become active participants in their healthcare decisions.
Chapters in this book address different issues faced by these patients,
including: what to expect during diagnosis, work-up, and treatment;
how to cope with treatment side effects; and what questions to ask
doctors.
1
Understanding Non-Hodgkin Lymphoma
Part 1 — Learning the Basics
Chapter 1: Understanding Non-Hodgkin Lymphoma
Part 1
Non-Hodgkin lymphoma (NHL) is a type of blood cancer that affects
specialized white blood cells called lymphocytes. Lymphocytes work
together with other cells in the immune system to defend the body
against invasion by bacteria, viruses, parasites, and other foreign
substances. Lymphocytes travel in the bloodstream and in a separate
network of vessels called the lymphatic system.
The sections in this chapter will explain these and other terms that will
help you understand NHL and how it affects a person’s health. A better
understanding of the disease will help patients take a more active role
in deciding the course of their treatment.
What is cancer?
Cancer is a group of diseases that develop when abnormal cells gain
the ability to divide abnormally and to spread to areas in the body
where they are not normally found.
Your body is made up of many different types of specialized cells that
are organized into tissues and organs to perform all the different tasks
needed to stay healthy. To keep things running smoothly, the cells in
your body grow, work, and divide in a very controlled fashion.
All of these cells also have a limited lifespan. Normally, a self-destruct
mechanism is triggered when a cell becomes too old or when it
stops working properly. However, sometimes damage to the genetic
material (DNA) of a cell gives it the ability to override this self-destruct
mechanism, allowing these abnormal cells to live longer or divide
more frequently than normal. Unless the body’s immune system gets
rid of them, these abnormal cells can multiply and cause cancer.
Learning the Basics
2
HOW CANCER FORMS INSIDE THE BODY
Abnormal
Cells Evade the
Immune System
Abnormal
Cells Multiply
(Cancer)
Tumors May Form
(Groups of
Abnormal Cells)
Most cancers are named after the organ or cell type of origin. For
example, a cancer that started in the pancreas is called pancreatic
cancer and a cancer that started in lymphocytes is called a lymphoma.
3
Understanding Non-Hodgkin Lymphoma
Why is there no single cure for cancer?
There are also smaller, but still important, differences in the cancer
cells found in different patients diagnosed with the same type of
cancer. Because of this, a treatment that may work very well in one
patient may not have the same positive effect in another. These are
some of the reasons why most cancers are much harder to treat or
prevent than, for example, bacterial or fungal infections, which typically
are caused by a single type of organism.
What is the lymphatic system?
As shown in the picture on page 5, the lymphatic system is a
circulatory system that is made up of a spidery network of thin tubes
called lymph vessels. Similar to blood vessels, lymph vessels branch
out into all tissues of the body. While people can clearly see blood
vessels, especially at their wrists and on the top of their hand, lymph
vessels are invisible to the naked eye.
Learning the Basics
4
Part 1
Cancer refers to a large group of very complicated diseases. A tricky
aspect of cancer is that there are many different ways for a cell to
become abnormal enough to develop into a cancer cell. Because of
this, the path taken by a liver cell to become a cancerous liver cell is
quite different from that taken by a lymphocyte to become NHL. This
is why a treatment that works against one type of cancer may not
necessarily work against another. There are also important differences
between different kinds of NHL, and a treatment that works against
one type of NHL may not necessarily be the best treatment choice for
another type.
ANATOMY OF THE IMMUNE SYSTEM
The immune system is the body’s defense against disease.
Tonsil
Thymus
Diaphragm
Lymph
nodes
Spleen
Lymph
vessels
5
Understanding Non-Hodgkin Lymphoma
Lymph fluid flows through lymph nodes and specialized lymph tissues
such as the spleen, tonsils, bone marrow, and thymus gland. Lymph
nodes filter lymph fluid, removing bacteria, viruses, and other foreign
substances from the body. If a large number of foreign substances
are filtered through a node or series of nodes, swelling may occur and
the nodes may become tender to the touch. Most swollen nodes are a
reaction to infection and are not cancerous.
What is a lymphoma?
A lymphoma is a cancer that affects lymphocytes, a type of white blood
cell. Lymphocytes travel through the blood and lymphatic system to
defend the body against foreign invaders like bacteria and viruses.
There are 2 major categories of lymphomas: non-Hodgkin lymphoma
(NHL) and Hodgkin lymphoma (HL). NHL is approximately 8 times
more common than HL; according to the American Cancer Society,
each year in the United States over 70,000 adults are diagnosed with
NHL and approximately 9,000 with HL. Both of these major categories
of lymphoma are further subdivided into several types that are different
in the way they develop and spread, and in how affected patients are
treated.
Lymphomas usually develop when a change, or mutation, occurs
within a lymphocyte, causing the abnormal cell to replicate faster than,
or live longer than, a normal lymphocyte. Like normal lymphocytes,
cancerous lymphocytes can travel through the blood and lymphatic
system and spread and grow in many parts of the body, including the
lymph nodes, spleen, bone marrow, and other organs. This is why
most types of NHL are found throughout the body by the time a patient
is diagnosed with the disease.
Learning the Basics
6
Part 1
Lymph vessels carry lymph, a type of liquid that contains lymphocytes.
Within this huge network of vessels are groups of small, bean-shaped
organs called lymph nodes. Thousands of lymph nodes are found
throughout the body, including the elbows, neck, armpits, chest,
abdomen, and groin.
What is non-Hodgkin lymphoma?
NHL does not refer to a single disease, but to a large group of related
cancers that occur in lymphocytes. NHL is the seventh most common
type of cancer affecting adults of both sexes.
The World Health Organization estimates that there are approximately
60 types of NHL. While these various types share many common
features, certain characteristics set them apart from each other,
including:
n
How they look when examined under a microscope.
n
Genetic characteristics and other molecular features.
n
How and where they grow in the body.
n
How their growth and spread affect patients.
n
How patients should be treated.
How are non-Hodgkin lymphoma types organized?
NHL is divided into the following 2 major groups:
n
n
7
B-cell lymphomas — These lymphomas develop from abnormal
B-lymphocytes (“B” because B-lymphocytes come from the bone
marrow) and account for 85% of all NHL.
T/NK-cell lymphomas — These lymphomas develop from abnormal
T-lymphocytes (“T” because normally T-lymphocytes spend part
of their lifespan in the thymus gland, a small organ in the chest) or
natural killer (NK) cells. These account for the remaining 15% of NHL.
Understanding Non-Hodgkin Lymphoma
RELATIVE FREQUENCIES OF B-CELL LYMPHOMAS
Follicular 29%
Diffuse large B-cell 37%
MALT 9%
Part 1
Mantle cell 7%
Chronic lymphocytic/
small lymphocytic 12%
Primary mediastinal large B-cell 3%
High Grade B, not otherwise specified 2.5%
Lymphoplasmacytic 1.4%
Burkitt 0.8%
Nodal marginal zone 2%
Splenic marginal zone 0.9%
RELATIVE FREQUENCIES OF T-CELL LYMPHOMAS
Peripheral T-cell, not
otherwise specified
25.9%
Angioimmunoblastic 18.5%
Extranodal natural
killer/T-cell 10.4%
Adult T-cell leukemia/
lymphoma 9.6%
Anaplastic large cell,
ALK+ 6.6%
Anaplastic large cell, ALK- 6.6%
Other disorders 12.2%
Unclassifiable peripheral T-cell 2.5%
Enteropathy-type T-cell 4.7%
Primary cutaneous anaplastic large cell 1.7%
Subcutaneous panniculitis-like 0.9% Hepatosplenic T-cell 1.4%
Learning the Basics
8
NHL types are also often grouped according to how quickly they grow:
n
n
Indolent lymphomas (also called low-grade lymphomas) grow slowly
and tend to cause few symptoms. While indolent lymphomas are
usually not curable, patients can live a long time with these types
of lymphomas because they respond well to treatment and may
potentially remain in remission for many years (even decades).
Over time, some indolent lymphomas may transform into aggressive
lymphomas.
Aggressive lymphomas (also called intermediate-grade and highgrade lymphomas) grow and spread more quickly than indolent
lymphomas. Aggressive lymphomas, while potentially lifethreatening, can often be cured with chemotherapy and other newer
treatments.
This table lists some of the main types of indolent and aggressive NHL.
Indolent Non-Hodgkin Lymphomas
Aggressive Non-Hodgkin Lymphomas
Follicular lymphoma
Diffuse large B-cell lymphoma (DLBCL)
Chronic lymphocytic leukemia/
small lymphocytic lymphoma
Burkitt lymphoma
Marginal zone lymphoma
Lymphoplasmacytic/Waldenström
macroglobulinemia
Lymphoblastic lymphoma
Mantle cell lymphoma
Peripheral T-cell lymphoma, unspecified
Anaplastic large-cell lymphoma
Mycosis fungoides/Sézary syndrome
(subtypes of cutaneous T-cell lymphoma) Angioimmunoblastic lymphoma
Blastic natural killer (NK)-cell lymphoma
Pathologists (doctors who specialize in disease diagnosis) can
distinguish among the many different types of NHL by examining
biopsy tissue samples under a microscope and by carrying out various
laboratory tests. This information is critically important in deciding how
to treat the affected patient.
9
Understanding Non-Hodgkin Lymphoma
Common types of aggressive non-Hodgkin B-cell lymphoma
Diffuse large B-cell lymphoma
DLBCL can arise in the lymph nodes or outside the lymphatic system.
It may be localized or generalized (spread throughout the body).
Despite being an aggressive lymphoma, DLBCL is curable.
The first sign of DLBCL is usually rapid swelling in the neck, armpit, or
groin caused by enlarged lymph nodes. Other symptoms include night
sweats, chills, unexplained fevers, and weight loss.
Mantle cell lymphoma
Mantle cell lymphoma affects approximately 6% of all patients with
NHL. This type of lymphoma usually affects men over 50 years. Often,
patients with mantle cell lymphoma have many lymph nodes, 1 or
more organs, and the bone marrow involved. The gastrointestinal
tract is a very common extra-nodal site of involvement. Mantle cell
lymphoma may sometimes follow an indolent, or slow-growing, course
but more typically behaves as an aggressive disease and is, therefore,
often treated as an aggressive lymphoma. For more information
on mantle cell lymphoma, please visit LRF’s “Focus on Mantle Cell
Lymphoma” website at www.focusonmcl.org.
Common types of indolent non-Hodgkin B-cell and T-cell
lymphoma
Follicular lymphoma
Follicular lymphoma (FL) is the second most common type of NHL.
FL accounts for about 22% of all NHLs. FL typically occurs in middleaged and older adults, but it can also affect younger adults. FL usually
appears in lymph nodes spread throughout the body. Often, one of
the first signs of FL is a painless swelling in the neck, armpit, or groin
caused by these enlarged lymph nodes. FL may eventually transform
Learning the Basics
10
Part 1
Diffuse large B-cell lymphoma (DLBCL) is the most common type of
NHL, accounting for up to one-third of newly diagnosed NHL patients.
The median age at diagnosis is 57 years, but the disease is also seen
in younger people.
into a more aggressive form of the disease. For more information on
FL, please visit LRF’s “Focus on Follicular Lymphoma” website at
www.focusonfl.org.
Chronic lymphocytic leukemia/small lymphocytic lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma
(SLL) are B-cell malignancies involving lymphocytes. The main
difference between the 2 diseases is where the cancer primarily
occurs. If the cancer cells are found mainly in lymph nodes, the
disease is called SLL. If the cancer cells are found in the bloodstream
and bone marrow, the disease is called CLL, although the lymph
nodes and spleen are often also involved.
Approximately 16,000 new cases of CLL and 5,000 new cases of SLL
are diagnosed annually. CLL/SLL are usually diagnosed in adults over
age 50; more than half of the people with CLL are over age 70.
Thinking of CLL/SLL as a lymphoma and not a form of leukemia is
important because CLL has a clinical course and treatment regimen
that is similar to other indolent lymphomas. Over time, CLL may
progress to a more aggressive type of lymphoma (Richter’s syndrome).
The staging system for CLL is different from the staging system
applied to other NHLs. For a more detailed description of CLL, visit
www.focusoncll.org or request a copy of the Lymphoma Research
Foundation’s publication entitled Understanding CLL/SLL: A Guide for
Patients, Survivors and Loved Ones.
Marginal zone lymphoma
Marginal zone B-cell lymphomas account for approximately 7% of all
NHLs. The median age of diagnosis of this type of lymphoma is 65.
These lymphomas include 3 basic types: (1) extranodal or mucosaassociated lymphoid tissue (MALT), occurring outside the lymph
nodes; (2) nodal, occurring within the lymph nodes; and (3) splenic,
occurring mostly in the spleen and blood. Skin-associated lymphoid-
11
Understanding Non-Hodgkin Lymphoma
tissue-related B-cell lymphoma (SALT) is also considered a form of
MALT lymphoma.
n
n
n
n
n
Part 1
Marginal zone and MALT lymphomas vary from other types of B-cell
NHLs in several ways:
Many people who develop MALT lymphoma have a history of
inflammation, infection, or autoimmune disorders.
Chronic inflammation is associated with Helicobacter pylori
(H. pylori), a microbial pathogen linked to chronic gastritis.
Sometimes, MALT lymphomas can be treated with antibiotics.
Different infections have also been implicated in other forms of
MALT lymphoma.
Hepatitis C virus infection has been associated with splenic marginal
zone lymphoma.
Waldenström macroglobulinemia
Waldenström macroglobulinemia (also known as lymphoplasmacytic
lymphoma or immunocytoma) is a rare B-cell lymphoma that occurs
in less than 2% of people with NHL. There are about 1,500 new cases
of Waldenström’s each year. The disease usually affects older adults
and is primarily found in the bone marrow, although lymph nodes and
spleen may sometimes be involved. People with Waldenström’s have
a high level of a protein called immunoglobulin M (IgM) in the blood.
These high levels of IgM can cause a thickening of the blood, resulting
in symptoms such as nosebleeds, headaches, dizziness, and blurring
or loss of vision.
Cutaneous T-cell lymphoma
Cutaneous T-cell lymphomas (CTCL), a group of lymphomas that
originate in the skin, are a subset of peripheral T-cell lymphoma
(PTCL). However, CTCL types are generally less aggressive, have
a different prognosis, and have different treatment approaches than
the aggressive PTCLs. Mycosis fungoides is the most common type
of CTCL. Sézary syndrome is an advanced, variant form of mycosis
fungoides, and affects both the skin and the peripheral blood.
Learning the Basics
12
Common types of aggressive non-Hodgkin T-cell/natural
killer cell lymphoma
Peripheral T-cell lymphomas
PTCL refers to a large number of different T-cell lymphomas that
together affect 5-10% of all patients diagnosed with NHL. This type of
lymphoma can occur anytime during adulthood.
Some varieties of PTCL are rare in the United States but can more
commonly be found in Asia, notably Japan, where an infection with
a virus called HTLV-1 is prevalent. Its presence makes it more likely
for an individual to develop a specific type of PTCL. It has also been
found in individuals coming from Caribbean countries. For more
information on PTCL, please visit LRF’s “Focus on Peripheral T-Cell
Lymphoma” website at www.focusonptcl.org.
Anaplastic large-cell lymphoma
Anaplastic large-cell lymphoma (ALCL) is rare, affecting about 3%
of adults with all types of lymphomas and 10-30% of children with
all types of lymphomas. ALCL occurs either systemically (meaning
in organs in the body) or cutaneously (meaning on the skin surface).
Systemic ALCL can respond well to chemotherapy and is potentially
curable. The cutaneous (skin) ALCL is a less aggressive disease that
is associated with a rare condition called lymphomatoid papulosis
(LyP), which is often a precursor to the development of cutaneous
anaplastic large-cell lymphoma.
Patients with systemic ALCL are divided into 2 groups, depending
on the expression of a protein called anaplastic lymphoma kinase
(ALK). The prognosis for ALCL depends on whether a patient is ALK
positive (expresses the protein) or ALK negative (does not express
the protein). ALK positive disease responds well to chemotherapy,
putting most patients in long-term remission or cure. A majority of
ALK negative patients will relapse within 5 years and are treated
more aggressively, often with transplant. For more information on
ALCL, please visit LRF’s “Focus on Anaplastic Large Cell Lymphoma”
website at www.focusonalcl.org.
13
Understanding Non-Hodgkin Lymphoma
Angioimmunoblastic lymphoma
Initially, AITL may be treated with steroids. However, the disease often
progresses and patients require chemotherapy and other medications.
In advanced cases, transplantation may be used.
Lymphoblastic lymphoma
Lymphoblastic lymphoma can appear in both B cells and T cells but
is much more common in T cells (which are affected in 80% of all
lymphoblastic lymphomas). This lymphoma is most often diagnosed
in children. With intensive chemotherapy, the complete remission
rate can be very high. The disease is often treated similarly to acute
lymphoblastic leukemia.
Blastic natural killer-cell lymphoma
Blastic natural killer (NK)-cell lymphoma is a very rare form of
lymphoma that affects the NK cells of the immune system. NK cells
are a type of lymphocyte that attack and destroy viruses and tumor
cells. This type of lymphoma usually affects older adults.
Patients with blastic NK-cell lymphoma have skin lesions that
are similar to those associated with leukemia, other cutaneous
lymphomas, and other skin diseases. It can only be diagnosed by
specific laboratory tests. This disease is hard to treat. The best
results have been obtained using a combination of chemotherapy and
radiation therapy, followed by bone marrow transplantation.
Learning the Basics
14
Part 1
Angioimmunoblastic lymphoma (AITL) affects 1-2% of all patients
with NHL in the United States. Symptoms include high fever, night
sweats, skin rash, and some types of autoimmune disorders, such as
autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic
purpura (ITP), in which the body does not recognize its own cells.
Because of this, the body makes antibodies against and destroys its
own cells or tissues, such as platelets (ITP) and red blood cells (AIHA).
Why do some people develop non-Hodgkin lymphoma?
The reasons why some people develop NHL are not well understood.
However, scientists have found that people with certain characteristics
have a higher risk of developing NHL compared with people who do
not have these characteristics.
The characteristics that make a person possibly more susceptible to
developing any type of disease are called risk factors. Having 1 or
more of these risk factors does not mean a person will develop NHL.
In fact, most people with risk factors never develop the disease and
many people diagnosed with NHL have never been exposed to any
clearly identifiable risk factors.
Known risk factors for NHL include:
n
n
n
n
n
n
15
A weakened immune system caused by an inherited immune
disorder (for example, hypogammaglobulinemia, Wiskott-Aldrich
syndrome), an autoimmune disease (for example, Crohn’s disease,
rheumatoid arthritis, psoriasis), or treatment with certain drugs used
after an organ transplant.
Infections with certain viruses, such as human immunodeficiency
virus (HIV which is the virus that causes AIDS), Epstein-Barr virus
(EBV), human T-cell leukemia/lymphoma virus (HTLV-1), hepatitis C
virus.
Infection with the bacteria Helicobacter pylori (which may cause
stomach ulcers and may increase the risk of developing lymphoma
in the stomach lining).
Older age—NHL may develop in children and adults of all ages but,
like most cancers, it is much more common in people older than 60
years of age.
Sex—NHL is more common in men compared with women.
Being exposed to certain chemicals such as benzene, certain
herbicides and pesticides, and some chemotherapy drugs used to
treat other cancers or autoimmune disease.
Understanding Non-Hodgkin Lymphoma
n
n
Treatment with radiation therapy for some other cancers,
including NHL.
Previous treatment for NHL.
Learning the Basics
16
Part 1
NHL cannot be caused by injury or by catching it from someone who
has the disease. The children and siblings of patients with NHL have
a slightly increased risk of developing this disease compared to the
general population. However, there are no clearly identified genetic
or hereditary factors to predict this slightly increased risk, and routine
screening for NHL is not recommended.
Part 1 — Learning the Basics
Chapter 2: Seeking Medical Help
This chapter explains the signs and symptoms of NHL and discusses
how a doctor determines whether or not a person has the disease.
A symptom is anything unusual in a normal body function,
appearance, or sensation that a patient experiences. During a visit
with a healthcare practitioner, patients should report all of their
symptoms to their doctor or nurse. Symptoms may indicate the
presence of lymphoma or another disease.
Signs are anything unusual that doctors or nurses notice when they
examine their patients.
What are the signs and symptoms of non-Hodgkin
lymphoma?
Some patients with NHL do not experience any symptoms. Their
disease may be detected initially by their doctor during a routine
physical examination or only after the tumor becomes large enough to
cause symptoms.
General symptoms of NHL can include:
n
Unexplained weight loss.
n
Fever for no known reason.
n
Drenching night sweats that soak clothing and sheets.
n
Severe or frequent infections.
n
Easy bruising or bleeding.
n
Numbness or tingling in feet and/or hands.
n
Headaches and/or blurry vision.
n
Fatigue.
17
Understanding Non-Hodgkin Lymphoma
Having one or more of these symptoms does not mean that a person
has NHL. These symptoms may be caused by an infection or other
conditions (including other cancers).
Signs and Symptoms
Possible Reason
Lumps under the skin on the sides of
the neck, in the groin or underarms, or
above the collar bone
This may be caused by swollen lymph
nodes which is a common symptom of
lymphoma
Swollen, tender abdomen (belly)
Enlarged lymph nodes in the abdomen
Accumulation of large amounts of liquid
in the abdomen
Enlarged spleen pressing on the
stomach (making a person feel full after
eating only a small amount of food)
Abdominal pain, nausea, or vomiting
Lymphoma in the intestine or causing
swelling near the intestine, possibly
blocking bowel movements
Stomach pain, nausea, and decreased
appetite
Lymphoma of the stomach
Coughing, trouble breathing, chest pain,
or pressure
Lymphoma in the chest which may press
on the windpipe (trachea)
Headache, trouble thinking, weakness
in certain parts of the body, personality
changes, and sometimes seizures
Lymphoma of the brain
Double vision, facial numbness, trouble
speaking
Lymphoma originating in other parts of
the body before spreading to the brain
and spinal cord
Itchy, red, or purple lumps or nodules
under the skin
Lymphoma of the skin
Learning the Basics
18
Part 1
NHL may cause different signs and symptoms depending on the
location of the tumor in the body. This table gives some examples of
signs and symptoms that may indicate the presence of a lymphoma
in a specific part of the body. Be aware that none of these signs and
symptoms are specific to NHL exclusively, and may be due to a variety
of other conditions.
When should a patient seek medical attention?
Anyone who has persistent symptoms should see a doctor to make
sure that lymphoma or another serious condition is not present. A
good rule of thumb is to seek medical attention if any of the previously
mentioned symptoms last longer than 2 weeks or sooner depending
on their severity and impact on a person’s daily life. Many of these
symptoms can arise from different causes and need not be cancer.
There are no specific tests that doctors can use to routinely screen
patients to see if they have NHL. During the visit with the doctor,
patients should describe all of their symptoms. The doctor will ask
detailed questions about medical history and perform a complete
physical examination. During the physical examination, the doctor will:
n
n
n
n
n
Check for swollen lymph nodes under the chin, in the neck and
tonsil area, above the shoulders, on the elbows, in the armpits, and
in the groin and upper legs.
Examine other parts of the body to see if there is swelling or fluid in
the chest or abdomen that may be caused by swollen lymph nodes.
Examine the abdomen to see whether any internal organs are
enlarged.
Ask about any pain experienced.
Look for any weakness or paralysis that may be caused by an
enlarged lymph node pressing against nerves or the spinal cord.
If doctors suspect lymphoma after reviewing the symptoms reported
and signs they have uncovered during the examination, they will order
other tests to confirm the diagnosis.
These tests should include a biopsy and may also include blood tests,
chest x-rays and other imaging tests, scans, and a bone marrow
evaluation. Depending on the type and location of the NHL, other tests
may be required. These tests and procedures are discussed in more
detail in the next chapter.
19
Understanding Non-Hodgkin Lymphoma
Part 1 — Learning the Basics
Chapter 3: Getting a Diagnosis
Cautions About Interpreting Diagnostic Reports
n
n
n
n
n
n
n
Only a biopsy is definitive.
Tests can be reported as “normal” even though lymphoma may
be present.
Tests may be reported as “abnormal” even though lymphoma is
not present.
Other conditions may mimic NHL.
The interpretation of tests, such as imaging studies and scans,
can be difficult in some situations and needs to be made in the
context of the disease and the patient.
Often, follow-up tests are needed to determine the true
significance of previous results; additional biopsies may be
needed to clarify the results.
Some patients like to review their written scan reports; when
doing so, it is important to carefully review the findings with their
doctor.
Learning the Basics
20
Part 1
Doctors need the results of different diagnostic tests to accurately
determine whether or not a patient has NHL. This chapter explains the
purpose of these different tests and describes what to expect during
and after these procedures.
How is non-Hodgkin lymphoma diagnosed?
The only way to be absolutely sure of a diagnosis of NHL (or any
cancer) is for a doctor to perform an excisional biopsy to remove an
entire lymph node or an incisional biopsy to remove a portion of the
diseased tissue (see below, “What is a biopsy?”). A pathologist will
examine a portion of this biopsy sample under a microscope to see if
it contains any lymphoma cells and, if possible, to identify the specific
type of lymphoma.
A surgical pathologist is a doctor who specializes in the diagnosis of
diseases by studying the cells from a patient’s blood, body fluids, and
tissue samples. A hematopathologist specializes in the pathology of
blood cells, and a lymphoma pathologist specializes in the diagnosis
and classification of NHLs and HLs. These doctors are trained to
recognize different cell types by looking at the shape and size of cells
and how they are grouped inside a tissue.
In addition to routine pathology analyses, portions of biopsy samples
will be used for other tests to confirm the diagnosis and to more
exactly identify the specific subtype of lymphoma. This chapter
explains how these tests work and what kind of information they
provide.
What is a biopsy?
A biopsy is a procedure in which a piece of tissue from an area of
suspected disease is removed from the body and examined under a
microscope. The information provided by this tissue sample is crucial
to correctly diagnose the disease and decide on the best course of
treatment.
21
Understanding Non-Hodgkin Lymphoma
The following are the 2 main types of biopsies doctors use for the
initial diagnosis of patients with a lymphoma:
n
n
n
Core
Needle
Biopsy
n
n
n
n
This type of biopsy is the best to establish an initial diagnosis of
lymphoma because it allows for the removal of bigger samples
than other biopsy procedures. The larger the sample, the more
tissue the pathologist can examine, which improves the accuracy
of diagnosis.
Part 1
Excisional
or Incisional
Biopsy
In this procedure, a surgeon cuts through the skin to remove an
entire lymph node (excisional biopsy) or a large portion of tissue
(incisional biopsy).
If the lymph node is close to the skin surface, the procedure can
be done under local anesthesia to numb the area. If the lymph
node is in the chest or abdomen, the patient is sedated and the
surgeon removes the tissue either laparoscopically (through
a tube inserted in the abdomen) or by performing abdominal
surgery.
This procedure is used when the lymph nodes are deep in the
chest or abdomen or in other locations that are difficult to reach
with excisional biopsy, or when there are medical reasons for
avoiding an excisional or incisional biopsy.
In this procedure, a large needle is inserted into a lymph
node suspected to be cancerous and a small tissue sample is
withdrawn.
A needle biopsy can be done under local anesthesia and stitches
are usually not required.
Sometimes the material collected may not be adequate for
diagnosis and a subsequent excisional or incisional biopsy may
be necessary.
A fine needle aspirate (FNA) biopsy is, as the name implies, a type of
biopsy performed with a very thin needle (smaller than that used for
a core needle biopsy). Because of the small needle size, the sample
will only contain scattered cells without preserving how the cells are
actually arranged in the lymph node. This limited information is not
enough for a precise diagnosis. An FNA biopsy is most often used to
check for return of the disease (relapse) and is virtually never used for
the initial diagnosis.
Learning the Basics
22
After a biopsy sample has been removed, it is examined by a
pathologist who develops a report. An oncologist then uses this report
along with results of other diagnostic tests to confirm a diagnosis. A
pathologic diagnosis and accurate classification of specific lymphoma
types can sometimes be difficult to make; if the pathologist’s
interpretation of the biopsy is uncertain, the results should be reviewed
by a hematopathologist or a lymphoma pathologist. Second opinions
can be helpful, because an accurate diagnosis is crucial in planning
the most appropriate treatment plan.
What are a bone marrow biopsy and a bone marrow
aspiration?
Bone marrow is a wet, spongy tissue inside bones where blood cells
are generated. A bone marrow biopsy involves removing a small
amount of bone marrow from inside a bone. The bone marrow is
then examined for the presence of lymphoma cells. A bone marrow
aspiration is similar to a bone marrow biopsy except it involves
removing only the liquid portion of the marrow, using a fine needle
inserted into a bone. A bone marrow biopsy or aspiration is not used
for initial diagnosis but is commonly used to see if the NHL has
spread, or to collect bone marrow for medical procedures such as
stem cell transplant or chromosomal analysis (see page 34, “Why
might a patient need to have another type of biopsy?”).
What questions should a patient ask the doctor before
having a biopsy or other diagnostic procedure?
Patients diagnosed with a complicated disease will be asked to
undergo a variety of procedures for the initial diagnosis and work-up
before treatment begins, during the course of treatment, and during
the follow-up period. Before patients agree to a procedure, they should
make sure that they understand the reasons for the procedure and
what will be involved. Here is a list of questions patients may want to
ask their doctor.
n
Why is this procedure necessary?
n
What will the procedure tell us about my condition?
23
Understanding Non-Hodgkin Lymphoma
Can the same information be obtained in another way?
n
What is involved in doing this procedure?
n
What are the possible risks, complications, and side effects?
n
Where will I have the procedure done?
n
Will I have to do anything to prepare for the procedure?
n
How long will the procedure take? Will I be awake? Will I feel pain?
n
How long will it take for me to recover from the procedure?
n
Should anyone else be present when I have the procedure?
n
Will I need someone to take me home afterward?
n
When will I know the results?
n
When will we talk about the results?
n
What will be my out-of-pocket costs?
Part 1
n
What is immunophenotyping?
Immunophenotyping is a process used during evaluation of biopsy
material to distinguish between different types of cells (for example,
between normal lymphocytes and lymphoma cells), by detecting
specific molecules (cell “markers” or “antigens”) found on the cell
surface. These cell markers are detected using special antibodies
grown and chemically modified in the laboratory so that they will
change color when they stick to their corresponding markers.
Learning the Basics
24
IMMUNOPHENOTYPING
Antibodies change color upon binding to specific cell markers.
Antibody
Antigen
This color change is studied under a microscope using
immunohistochemistry (IHC) analysis or sorted and counted using
a process called flow cytometry. Sometimes, both IHC and flow
cytometry are necessary for accurate immunophenotyping.
25
Understanding Non-Hodgkin Lymphoma
Immunohistochemistry
(IHC)
n
n
Flow Cytometry
n
n
n
Part 1
n
In this test, thin slices of the biopsy sample (or
thin layers of fluid or blood) are placed on slides
and treated with sets of antibodies that recognize
different markers found in different types of
lymphoma cells and normal lymphocytes.
The pathologist examines the slides under a
microscope to look for the visible color change that
happens when the antibody sticks to the marker.
The pathologist identifies and counts the number
of cells that change color (meaning that they are
positive for the marker) with each of the different
antibodies and uses that information to identify the
specific type of lymphoma.
In this test, cells from the biopsy sample are placed
in a liquid solution and treated with sets of antibodies
that recognize different markers found in different
types of lymphoma cells.
The cell-antibody mixture is injected into an
instrument called a flow cytometer. This machine
uses laser beams to sense the different colors
the cells emit because of the different antibodies
attached to them. This information is measured and
analyzed by a computer.
The results from the flow cytometry analysis will
distinguish between different types of lymphoma,
other cancers, or some other disease.
Learning the Basics
26
What is cytogenetic analysis?
Chromosomes are long strands of DNA, the genetic material of a
cell. Healthy human cells have 23 pairs of chromosomes. Some
lymphomas and other types of cancer have too few or too many
chromosomes, or have abnormal chromosome structures. In
cytogenetic analysis, chromosomes from a patient’s lymphoma cells
are examined under a microscope to check for changes in their
number (too few or too many) or the presence of other abnormalities.
One type of chromosomal abnormality that can be seen through
a microscope is called a translocation—which happens when part
of a chromosome breaks off from its normal location and becomes
attached to another chromosome. The results of the cytogenetic
analysis can help distinguish between different types of NHL.
CHROMOSOME TRANSLOCATION
Two different chromosomes exchange
portions of their genetic material.
Chromosome 14
Chromosome 18
Bcl2
Bcl2
Translocation
It usually takes 1 to 2 weeks to get the results from cytogenetic testing
because a sufficient number of patient’s lymphoma cells must be
grown in the laboratory to get enough genetic material for the analysis.
27
Understanding Non-Hodgkin Lymphoma
Part 1 — Learning the Basics
Chapter 4: Work-up Before Treatment Can Begin
Part 1
After the initial diagnosis of NHL, the doctor may order other tests
such as blood tests, molecular genetics tests, imaging studies, heart
and lung function tests, and, less frequently, additional biopsies. This
process is often called the work-up. Some of these work-up studies
are needed to see if and how much the disease has spread to other
parts of the body. Doctors will use these test results to determine the
stage of a patient’s disease. Other tests will check how the disease
has affected a patient’s overall health and major organ functions.
Together all of these tests will provide the information needed to help
patients and their doctors decide on the course of treatment that will
give patients the best chance for curing the disease or putting it into
a lasting remission. This chapter will help you understand how NHL
is staged, the reason for the various tests, how these tests work, and
what to expect.
How is non-Hodgkin lymphoma staged?
Staging is used to describe how widely the lymphoma has spread in
adult patients with NHL. As shown in the following figure, there are
4 main stages of lymphoma, designated by the Roman numerals
I through IV. This staging system divides the body in half using
the diaphragm, the muscle that divides the chest cavity from the
abdominal cavity.
Learning the Basics
28
STAGING OF NON-HODGKIN LYMPHOMA
Stage I:
• Localized
disease
• Single lymph
h
node region
• Single organ
outside lymph
ph
nodes
Stage II:
• Two or more
lymph node
regions near
each other
• One or more
lymph nodes
and one organ
near each other
Stage III:
• Two or more
lymph node
regions in
different parts
of the body
with or withoutt
involvement
of a nearby
organ or the
spleen
Stage IV:
• Widespread
W
disease
dis
d
• Multiple
organs
M
• With
W or without
lymph
lyym node
involvement
inv
Your doctor may also add any of the following single letters to the
stage.
n
n
n
A — if patients have not experienced symptoms such as significant
weight loss (more than 10% in 6 months), drenching night sweats,
or fevers.
B — if patients have lost weight (more than 10% in 6 months) and
have experienced drenching night sweats or fevers.
X — if patients have a lymphoma that is greater than 10 cm (4
inches) wide. This is also called bulky disease.
Being diagnosed with stage III or IV NHL is common. Keep in mind
that these advanced stages can be successfully treated.
29
Understanding Non-Hodgkin Lymphoma
What is the purpose of blood tests?
Part 1
Doctors will test a patient’s blood to measure the quantity of the
different types of cells (red blood cells, white blood cells, and
platelets). This information can help determine how advanced the
lymphoma is. These blood tests will most likely include: a complete
blood count (CBC), differential (to measure the relative amounts
of different types of white blood cells), platelets, and serum lactate
dehydrogenase (LDH). Fast-growing lymphoma can cause very high
blood levels of LDH.
Doctors will also most likely order a comprehensive metabolic panel
to measure the amount of different chemicals in your blood, which will
show whether the lymphoma is affecting the main body organs. The
comprehensive metabolic panel usually includes 14 specific tests that
measure the function of the kidneys and liver, electrolyte balance,
acid/base balance, blood sugar, and different blood proteins. Calcium,
magnesium, potassium, and sodium are some of the electrolytes
found in your body; abnormal levels of electrolytes can make you sick.
Depending on the type of lymphoma, the blood may also be tested for
signs of infection with hepatitis B virus (HBV), hepatitis C virus (HCV),
or human immunodeficiency virus (HIV). A serum immunoglobulin
test (immunoelectrophoresis) may also be performed to test for the
presence of certain immunoglobulins (a type of protien) that are
sometimes found with certain NHL types.
The results from these tests will help patients and their doctors decide
between different types of treatments. Many of these blood tests will
be repeated during the course of treatment to check how the treatment
is affecting the patient’s body functions.
What is the purpose of molecular genetic tests?
Doctors may order molecular genetic tests to confirm the cytogenetic
tests and find out more detailed information about the types of damage
to the genetic information of the lymphoma cells in the patient’s body.
Learning the Basics
30
The 2 main types of molecular genetic tests used are:
Fluorescent In Situ
Hybridization (FISH)
n
n
Polymerase Chain
Reaction (PCR)
n
n
FISH uses fluorescent chemicals to specifically
attach to certain parts of chromosomes to show
the presence of translocations and other large
abnormalities.
FISH can be done on blood or bone marrow samples
and the test results are usually available within a few
days (quicker than cytogenetic testing).
PCR is a test that can detect changes in DNA that
are too small to be seen under a microscope, or
using cytogenetic analyses or FISH.
PCR tests can be done on a very small quantity
of lymphoma cells; using this technique, abnormal
areas of DNA reproduce in an exponential fashion
until they are large enough to be detectable.
What types of imaging tests may be used?
A patient’s doctor will most likely order imaging tests to help find areas
of the body where there may be cancer, to learn how far the cancer
has spread, and later on to check how well the treatment is working.
Most of these tests are painless and no anesthetic is required.
Several types of the following imaging procedures may be needed to
thoroughly evaluate the extent of your disease.
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Understanding Non-Hodgkin Lymphoma
X-ray
n
Computer
Tomography
(CT) Scan
n
n
n
n
Magnetic
Resonance
Imaging (MRI)
n
n
n
Findings on a chest x-ray may indicate whether the disease is
“bulky.”
A CT scan takes x-rays from many different angles around the
body. A computer combines the pictures obtained from these
different angles to give a detailed image of organs inside the
body.
Patients with NHL often have CT scans of the neck, chest,
abdomen, and pelvis to find out how many lymph nodes are
involved, how large they are, and whether internal organs are
affected by the disease.
The amount of radiation exposure during a CT scan varies
depending on the area scanned. Most CT scans confer little
risk to the patient, although CT scans of the abdomen and
pelvis do add a moderate amount of risk (1 in 500-1,000) to
the general lifetime risk of cancer.
Before a CT scan, the patient may be asked to drink a
contrast liquid and/or get an intravenous injection of a
contrast dye that will more clearly outline abnormal areas that
may be present in the body.
Like a CT scan, an MRI takes images from different angles
around the body, but an MRI does not use x-rays like a CT
scan; instead it uses magnets and radiofrequency waves.
Therefore, an MRI confers no risk of radiation-induced
cancer.
An MRI can provide important information about tissues and
organs, particularly the nervous system, that is not available
from other imaging techniques.
Because this testing technique works well to get clear images
of the bones, brain, and spinal cord, an MRI may be ordered
if a doctor wants to see whether the lymphoma has spread in
these areas.
Learning the Basics
32
Part 1
n
X-rays use radiation to take pictures of areas inside the body.
The amount of radiation used in most diagnostic tests is so
small that it poses little risk to the patient.
Positron
Emission
Tomography
(PET) Scan
n
n
n
n
This test evaluates NHL activity in all parts of the body.
To perform the test, radioactive fluorodeoxyglucose (a type of
sugar) is first injected into the body. A positron camera is then
used to detect the radioactivity and produce cross-sectional
images of the body. The amount of radiation used for a PET
scan is low and poses little risk to a patient.
PET scans help determine how much disease is present
(staging) and how well it is responding to treatment.
While CT scans show the size of a lymph node, PET scans
show if the lymph node is active (still has disease). CT and
PET scans are now combined into 1 test (PET/CT).
What is a MUGA scan?
A MUGA scan (multi-gated acquisition scan) is an imaging test that
looks at how well the heart muscle is working. A MUGA scan is done
to make sure that the patient’s body can withstand treatment with
certain lymphoma drugs that may damage the heart in rare cases.
MUGA scans may be done when patients are resting or exercising,
depending on what their doctor wants to assess.
A doctor will most likely order a MUGA scan if he or she is considering
treating a patient with the drug doxorubicin (Adriamycin). This test is
needed to make sure that the heart is functioning normally because
doxorubicin may be associated with cardiac toxicity. A 2-dimensional
echocardiogram (ECHO) is sometimes used instead of the MUGA
scan to test heart function.
33
Understanding Non-Hodgkin Lymphoma
Why might a patient need to have a lung function test?
Why might a patient need to have another type of biopsy?
Once the diagnosis of NHL is made, the doctor may order other types
of biopsies for additional pathology studies and other tests to see if
and how the disease has spread to other parts of the body. With this
information, the doctor can properly stage the disease.
Bone Marrow
Aspiration and
Biopsy
n
n
n
n
n
This procedure may be done to determine if the lymphoma
has spread to the bone marrow.
The bone marrow is the spongy, soft material found inside
our bones where normal blood cells are generated. NHL can
spread to the bone marrow or start in the bone marrow.
For the aspiration part of this procedure, the doctor cleans
and numbs the skin over the hip and inserts a thin hollow
needle into the bone. The doctor uses a syringe to remove a
small amount of liquid from the bone marrow. Even with the
numbing local anesthetic, this procedure can be painful for a
few seconds while the marrow is withdrawn.
For the biopsy part of this procedure (which is usually done
right after the aspiration), the doctor inserts a slightly larger
needle to take out a small piece of bone and marrow. This
procedure may also cause mild pain or a pressure sensation.
The procedure does not require any stitches.
Patients who are anxious about the test should talk with their
doctor and nurse to see whether taking a calming medication
before the procedure would be helpful.
Learning the Basics
34
Part 1
Lung function tests are done to make sure that the body can withstand
treatment with certain lymphoma drugs that may stress a patient’s
lung function (e.g., bleomycin, cyclosphophamide). A doctor may order
breathing tests before beginning treatment and at other times during
treatment to make sure that a patient’s lungs are still working properly.
Lumbar
Puncture
(Spinal Tap)
n
n
n
n
Pleural or
Peritoneal
Fluid
Sampling
n
n
n
35
Sometimes this procedure is used to determine if the
lymphoma has spread to the cerebrospinal fluid (CSF), the
liquid found in the brain and spinal cord. Most types of NHL
do not spread to the CSF.
The doctor will order this test only for patients with certain
types of lymphoma or who have symptoms suggesting that
the disease has reached the brain.
For this procedure, the doctor inserts a thin needle into the
lower back after the area has been numbed with a local
anesthetic. The doctor then uses a small needle to remove a
sample of fluid that will be sent to the lab for analysis.
A lumbar puncture can also be used to deliver small amounts
of chemotherapy (usually cytarabine or methotrexate) directly
into the fluid that bathes the brain.
This procedure is used to find out if the lymphoma has
spread to the chest or abdomen where it can cause liquid to
accumulate.
For this procedure, the doctor numbs the skin with a local
anesthetic, inserts a small needle, and uses a syringe to
remove a sample of the liquid for laboratory analysis.
The liquid is called pleural fluid when found inside the chest
and peritoneal fluid when found inside the abdomen.
Understanding Non-Hodgkin Lymphoma
Part 2 — Treatment of
Non-Hodgkin Lymphoma
Chapter 5: What You Should Know Before Starting Treatment
First Steps to Take After Receiving a Diagnosis
n
n
Take care of yourself (eat, sleep, rest, and exercise).
Seek the support of family, friends, and others on whom you
trust and rely.
n
Learn about the disease and treatment options.
n
Find medical care that meets your needs.
n
Find emotional and social support.
n
Understand the cost of care and what your insurance will cover.
n
TIP
NT
PATIE
Maintain a copy of your medical records (paperwork, test
results, your own notes).
Who will plan and carry out the treatment?
The treatment of patients with NHL is usually overseen by a medical
oncologist or hematologist who specializes in the treatment of patients
with lymphoma and/or blood diseases. Depending on the patient’s
healthcare needs, the doctor may refer him or her to work with
specialists such as a surgical oncologist and a radiation oncologist.
The patient’s healthcare team will also include other healthcare
professionals such as an oncology nurse, nurse practitioner, physician
assistant, social worker, and registered dietitian. The healthcare team
will work together and communicate with you to plan, carry out, and
monitor the treatment.
Treatment of Non-Hodgkin Lymphoma
36
Part 2
Getting a cancer diagnosis is an overwhelming experience. It is
perfectly normal to be shocked by the diagnosis, anxious about the
future, and confused about the medical information and decisions that
need to be made. This chapter will help you prepare for the start of
treatment by explaining the next steps and providing tips for talking
with a patient’s doctor about your questions and concerns.
What is a prognosis?
Prognosis is the medical term doctors use for predicting how the
disease will progress and the likelihood for recovery. Prognosis is
usually based on information gathered from hundreds or thousands
of other patients who have had the same disease. This statistical
information provides doctors with a general idea of what to expect
when a patient is diagnosed with a specific type of NHL, and also
gives guidance on the kinds of treatments that have been most
successful in treating that NHL type.
Keep in mind that no two patients are alike and that statistics from
large groups of people cannot accurately predict what will happen
to a specific patient. The doctor most familiar with the patient’s
situation is in the best position to help interpret these statistics and
understand if and how they may apply to a patient’s particular situation.
How will we decide what is the best treatment?
There are many effective treatment options for patients with NHL. To
identify which treatments may work best, doctors consider the following:
n
The type of NHL.
n
The stage and location of the lymphoma.
n
The presence or absence of lymphoma symptoms.
n
n
How quickly the lymphoma is growing (whether it is an indolent or
aggressive lymphoma).
Levels of the proteins lactate dehydrogenase (LDH) and beta-2
microglobulin (B2M) in the patient’s blood—higher levels of LDH or
B2M suggest that the lymphoma may be in a more advanced stage or
an aggressive type. People who have normal levels of these proteins
appear to have better outcomes than those with higher levels.
n
A patient’s overall health and age.
n
A patient’s preferences.
n
37
Whether the treatment is the first the patient has received or if the
disease has returned after prior therapy.
Understanding Non-Hodgkin Lymphoma
A doctor will discuss the risks, benefits, and side effects associated
with the different treatment choices applicable to the patient’s
particular situation. Share questions and concerns with the doctor so
that together you can decide which option is best. Use the following
questions to help you make an informed decision.
Questions to Ask Before Treatment Begins
n
n
n
What is the stage of my disease? Where are the tumors?
What are my treatment choices? Which do you recommend for
me? Why?
Are new treatments being studied? Would a clinical trial be
appropriate for me?
n
Do I need more than one type of treatment?
n
What is the goal of treatment?
n
n
n
n
Part 2
n
What is my exact diagnosis? May I have a copy of the report
from the pathologist?
TIP
NT
PATIE
What are the expected benefits of each type of treatment? How
will we know if the treatment is working? What tests will I need
to have to check if it works? How often will I need to get tested?
What are the risks and possible side effects of each treatment?
Can these side effects be prevented or controlled?
What should I do to take care of myself during treatment?
Are there any late or long-term side effects that I should be
aware of?
n
How long will the treatment last?
n
What are the chances that the treatment will be successful?
n
How will the treatment affect my normal activities?
n
How often will I need a checkup?
n
How much will the treatment cost? Will my insurance cover it?
Treatment of Non-Hodgkin Lymphoma
38
When should a patient get a second opinion?
Before starting any type of treatment, a patient may consider getting
a second opinion—especially if some characteristics of the diagnosis
are complicated or uncertain. The purpose of the second opinion
is not to question the doctor’s expertise but to make sure that the
suggested treatment plan is reasonable and optimal for the patient’s
particular case. Do not be concerned that you will offend your doctor
by requesting a second opinion. Most doctors will be supportive and
helpful if you tell them that you would like to get a second opinion.
Ask the doctor if it would be okay to briefly delay the start of treatment
to give extra time to get a second opinion. Keep in mind that some
insurance programs require second opinions; others may cover it if a
patient or doctor requests it.
Getting a Second Opinion
n
n
n
39
Some hematologists/oncologists/lymphoma specialists
associated with medical schools or cancer centers may provide
a consultation and be willing to work together with a local
oncologist to provide treatment and follow-up care.
As part of the second opinion, another pathologist must review
the tissue and blood samples to confirm the diagnosis. Ask
your doctor about finding a pathologist with a lot of experience
diagnosing patients with lymphoma.
To get a second opinion, you will have to provide the consulting
doctor a complete copy of all medical records, original x-rays,
pathology materials, scans, and reports. When you set up the
appointment, ask their office for a list of all the materials they
will need. It may be useful to keep your own copy of all these
records in case you have questions or concerns later on.
Understanding Non-Hodgkin Lymphoma
TIP
NT
PATIE
To identify lymphoma specialists to contact for a second opinion:
n
n
n
n
n
Contact the patient referral service at your local hospital and
at the nearest hospital associated with a medical school; many
hospitals have online directories that can be searched to find a
specialist in your area.
Visit the American Society of Clinical Oncology (ASCO) at
www.cancer.net to search their oncologist database.
Part 2
n
Ask your current doctors, family members, other patients,
friends, and coworkers.
Visit the American Society of Hematology (ASH) at
www.hematology.org/patients to search for hematologists with
an interest in lymphoma.
Visit the National Cancer Institute (NCI) at
http://cancercenters.cancer.gov/ to identify the nearest
NCI-designated cancer center and call or visit their website to
find out about their lymphoma specialists.
Visit the American Board of Medical Specialists (ABMS) at
www.abms.org and click on, “Is My Doctor Board Certified” to
find out if doctors are board certified in a particular specialty.
How to find an oncologist and treatment center
A patient’s primary care doctor will probably have referred them to a
specialist—likely a medical oncologist, hematologist, or hematologist/
oncologist. Oncologists are physicians who specialize in diagnosing
and treating patients with cancer. Hematologists are physicians who
specialize in diagnosing and treating patients with disorders of the
blood and lymphatic system. Many physicians are experienced in both
areas, and there is some overlap.
Before agreeing to treatment by a specific specialist and treatment
center, make sure that they will be able to meet all medical and
personal needs. Patients should feel comfortable with the healthcare
team and the quality of the care they provide.
Treatment of Non-Hodgkin Lymphoma
40
Here are some questions to ask to select the best medical team:
n
n
n
n
n
n
n
n
n
n
n
n
What are the credentials of the specialist, the other members of
the medical team, and the hospital or cancer center?
Is the specialist board certified as a medical oncologist and/or
hematologist? Has he or she passed qualifying examinations by
the American Board of Internal Medicine to certify competency
in these specialties?
How much experience do the specialist and treatment center
have in treating patients with cancer in general, and NHL in
particular?
How many patients with this disease are being treated here
now?
Does the specialist and/or center participate in clinical trials?
How much time does the specialist spend on research and how
much on the treatment of patients with NHL?
Is the specialist a member of the American Society of Clinical
Oncology and/or the American Society of Hematology?
Does the clinic or center have modern surgical facilities and
diagnostic equipment?
Is the specialist or clinic affiliated with any major medical center
or medical school?
What arrangements are made for medical coverage after hours
and on weekends, in case of an emergency?
Is my health insurance accepted at this center? Will the office
file claims for reimbursement and process the paperwork?
What kind of patient resources does the clinic or cancer center
have for patients with my disease?
Patients enrolled in a managed care program may have limited
choices. However, patients have the right to choose another
healthcare team if they are not entirely satisfied with their first
consultation visit. They should talk with other patients about their
experience and ask them if they would recommend their specialist and
healthcare team. Also, patients should share any concerns with their
41
Understanding Non-Hodgkin Lymphoma
primary doctor and ask for a referral to a different specialist if they are
not satisfied after their first visit.
How to communicate with the healthcare team
A good first step is to write down all questions that come to mind.
Before meeting with a doctor or nurse, whether for the first time or for
follow-up visits, consider organizing these questions to bring to the
visit. Put the 2 or 3 most important questions at the top of your list,
since time with doctors or nurses may be limited. But make sure that a
member of the medical team reads all of your questions, because they
may see some that are more important than you realize.
Patients should consider having a family member or close friend
accompany them to the doctor’s office or clinic to help ask questions
and understand and remember answers. A companion could also
help by taking notes during the visit. Some patients bring a recording
device to record the answers. Check with the patient’s doctor before
recording any conversations.
Most oncology nurses are also very well informed about cancer
treatments and are a good source of information on a wide range
of topics. Oncology social workers are also available to assist with
practical and emotional needs from the time of diagnosis and onwards.
Although family members are often very concerned about their loved
one and want information concerning his or her care, confidentiality
rules prohibit doctors from giving out information to anyone without
the patient’s expressed permission. For efficiency, designate 1
family member as the family contact. The patient must remember to
specifically tell the doctor the identity of the primary family contact.
Treatment of Non-Hodgkin Lymphoma
42
Part 2
Patients can ease their anxieties by establishing open, honest
communication with their doctor and nurse regarding their diagnosis,
and learning about what the prescribed treatment regimen is,
how it works, what tests are involved, and what side effects and
complications may be associated with it.
Communicating With Your Doctors
At home
n Keep a journal of your symptoms to help you remember the
details you want to discuss with your doctor during your next
office visit.
n
TIP
NT
PATIE
Make a list of questions that you want to ask your doctor—but
if the questions are urgent, do not wait for the next visit; call the
doctor’s office to discuss your concerns.
At your next doctor’s visit
Bring your symptom journal and list of questions, and discuss
them with your doctor or nurse.
n
n
n
n
n
n
n
Ask a family member or friend to come with you to provide
emotional support and take notes.
Do not be afraid to ask questions if you do not understand
something. Your doctor will want to know if you are uncertain or
confused, and will be happy to explain things to you.
Clarify who should be contacted for specific sorts of questions,
or for weekend support.
Ask if members of your healthcare team communicate by email.
Before leaving the doctor’s office, make sure that you
understand the next steps in your care.
Ask for written information that you can take home to help you
remember what to do, and learn more about your treatment.
What is the purpose of an Advance Healthcare Directive
and Appointing a Healthcare Proxy?
Having an Advance Healthcare Directive (a living will) and appointing
a Healthcare Proxy is something that all adults should consider doing
regardless of their healthcare status. This is something for everybody
to think about, not just people with cancer—accidents and other
unforeseen circumstances can happen at any time.
43
Understanding Non-Hodgkin Lymphoma
Writing down your wishes for critical medical care in an Advance
Healthcare Directive is a way for you to formally tell your doctor, family
members, and friends about your healthcare preferences and what
special treatments you do or do not want if you were critically ill or
injured and unable to make and communicate your own decisions.
Part 2
Besides stating medical care instructions, the Advance Healthcare
Directive should also include the name of your Healthcare Proxy,
or decision maker. This person should be someone you believe will
carry out your wishes if you are unable to do so, including any do not
resuscitate (DNR) instructions.
Before writing an Advance Healthcare Directive, it is important that you
understand patients’ rights and laws regarding Advance Healthcare
Directives in your state. Consulting an attorney can provide the legal
information, but patients do not have to use an attorney to write an
advance directive. Make sure that your Advance Healthcare Directive
includes:
n
n
Specific instructions on medical care, including the types of
special treatment you do or do not want, such as cardiopulmonary
resuscitation (CPR), artificial respiration, drugs to make the heart
function, kidney dialysis, artificial feeding, and certain surgical
procedures.
Your choice of a healthcare proxy.
For more information about Advance Healthcare Directive guidelines
for your state, please visit the “Caring Connections” website of the
National Hospice and Palliative Care Organization, at
www.caringinfo.org.
Treatment of Non-Hodgkin Lymphoma
44
How to be a self-advocate
Being a self-advocate and an active participant in your healthcare can
be a positive experience and may help restore any sense of control
you may have felt was lost following your diagnosis. All patients should
remember that they are partners in their treatment plan. Many patients
feel better when they actively participate in their care.
The first steps in participating in treatment are to ask questions,
learn about options, and work closely with the doctor. Patients must
be comfortable with their doctor and the approach that they take. If
you are not comfortable, you should openly discuss your concerns.
Confidence in the medical team often leads to confidence in treatment.
If you do not feel that the team is a good match, you should ask for a
referral.
Questions will likely vary depending on the purpose of the meeting
with the oncologist (such as the initial visit to discuss the diagnosis or
a routine visit to monitor a remission). Ask for the timing of office visits,
treatments, and tests. The doctor can help explain what the tests will
look for and define the possible responses and the options for further
care depending on treatment response.
Although each person is different and each response to therapy is
unique, knowing someone who has been through the same treatment
and who may have had similar concerns can be a source of great
comfort for patients. If you are interested in talking to and learning
from people who have had similar experiences, you should ask your
oncologist, hematologist, oncology nurse, or the oncology social
worker about any support groups in their area.
Before you agree to any tests, you should check with your healthcare
team to determine which costs are covered by insurance and which
are not. You should also not be afraid to talk to your healthcare team
about nonmedical issues, such as transportation, finances, insurance,
and childcare.
45
Understanding Non-Hodgkin Lymphoma
Self-Advocacy
n
n
n
Learn more about your specific lymphoma by asking your
doctor for information and visiting reliable websites, such as the
Lymphoma Research Foundation at www.lymphoma.org.
Take advantage of counseling, support groups, nutritional
counseling, fitness classes, and other services offered at your
doctor’s office, cancer center, or hospital.
Part 2
n
Do not be afraid to ask your doctor or nurses questions about
your care.
TIP
NT
PATIE
Consider joining the Lymphoma Support Network, a nationwide
buddy program that matches patients and caregivers with
people who had similar experiences. For information about the
program, call (800) 500-9976 or email [email protected].
Treatment of Non-Hodgkin Lymphoma
46
Part 2 — Treatment of
Non-Hodgkin Lymphoma
Chapter 6: Treatments for Non-Hodgkin Lymphoma
In this chapter, you will learn about the most common therapies that
are currently used in the treatment of patients with NHL. Keep in mind
that new therapies may have been approved by the United States
Food and Drug Administration (FDA) since this book went to print.
Read Chapter 10 to learn more about new agents under investigation.
What words do doctors use to describe the outcome of
treatment?
Primary
Therapy
This is the first therapy that a patient receives. The choice of
primary therapy depends on the pathologic characteristics of the
disease, including the factors described previously in this booklet.
Complete
Remission
(CR)
This term is used when all signs of the lymphoma have disappeared
after treatment. This does not mean that the cancer is completely
cured; it means that the symptoms have disappeared and the
lymphoma cannot be detected using current tests. If this response is
maintained for a long period, it is called a durable remission.
Cure
This word is cautiously used by doctors when there are no signs
of the lymphoma reappearing after many years of continuous,
complete remission. The term is most often applied to diffuse large
B-cell lymphoma or Hodgkin lymphoma.
Disease
This term means that the disease has worsened or the tumor
Progression has grown during therapy. Other terms used to describe this are
treatment resistance or resistant disease.
Partial
Remission
(PR)
This term is used if the lymphoma has responded to treatment and
shrunk to less than one-half of its original size.
Improvement This term is used if the tumor has shrunk following therapy but is
still more than one-half of its original size.
Stable
Disease
47
This term means that the disease has not gotten worse or better
following therapy (the tumor has not grown or shrunk), but has
stayed about the same size.
Understanding Non-Hodgkin Lymphoma
Refractory
Disease
This refers to a cancer that is resistant to treatment (meaning that it
has not disappeared after treatment).
Relapse
This term refers to disease that reappears or grows again after a
period of remission.
What types of treatments are used in patients with NHL?
There are 3 general types of therapies for patients with NHL:
n
n
Part 2
n
Radiation therapy, which uses high-energy radiation to kill cancer
cells.
Chemotherapy, which affects general cell growth and division.
Biological therapy, which works with the body’s normal functions
(such as the immune system) to fight cancer.
These therapy types are described in detail throughout the chapter.
What is watchful waiting?
With the watchful waiting approach, patients do not receive any antilymphoma treatments but their health and disease are monitored
through regular checkup visits and follow-up evaluation procedures,
such as laboratory and imaging tests. These patients continue to
remain untreated as long as they do not have any symptoms and
there is no evidence that the lymphoma is growing or spreading.
Doctors recommend watchful waiting for selected patients with
indolent lymphoma. This approach may be started after the initial
diagnosis or after relapse, depending on the situation. Active treatment
is started if the patient begins to develop lymphoma-related symptoms
or if there are signs that the disease is progressing.
Watchful waiting is not a treatment option for patients with aggressive
lymphomas. Usually, treatment for these patients should start as soon
as possible after diagnosis.
Treatment of Non-Hodgkin Lymphoma
48
Questions to Ask
Before Starting Watchful Waiting
n
What happens if I choose watchful waiting and then change my
mind?
n
Will the disease be harder to treat later?
n
How often will I have checkups?
n
TIP
NT
PATIE
Between checkups, what symptoms and other problems should
I report?
What is chemotherapy?
Chemotherapy drugs work against general characteristics of cancer
cells such as their tendency to grow and multiply very quickly.
Depending on the drug, patients may have to swallow a pill or receive
it through a liquid infused directly into a vein (intravenous infusion
or IV). A few chemotherapy drugs have to be injected in the space
around the spinal cord, using a lumbar puncture.
During chemotherapy, patients receive the drug or drugs 1 or more
times a week for 1 or more weeks, followed by a rest period. This
regular treatment schedule is called a cycle. The length of the rest
period and the number of cycles vary depending on your disease and
the type of drugs used.
Most patients with NHL are treated with combination chemotherapy,
meaning 2 or more drugs, instead of a single drug. These
chemotherapy drugs are given in a specific order (or schedule) during
certain days of each treatment cycle—this is called a treatment
regimen. The reason to combine drugs is to increase how effectively
they kill or damage cancer cells.
Oncology nurses are usually responsible for administering the
chemotherapy regimen prescribed by the doctor. Most patients
receive their chemotherapy in an outpatient clinic, hospital outpatient
49
Understanding Non-Hodgkin Lymphoma
department, or doctor’s office, but sometimes patients have to stay in
the hospital for their treatment.
Common chemotherapy regimens for non-Hodgkin
lymphoma
Regimen
Abbreviation
Common Treatment(s)
B
Bendamustine (Treanda)
C
Cyclophosphamide (Cytoxan)
Chl
Chlorambucil (Leukeran)
CVP (COP)
Cyclophosphamide (Cytoxan)
Vincristine (Oncovin, Vincasar PFS)
Prednisone (Deltasone)
CHOP
Cyclophosphamide (Cytoxan)
Doxorubicin/hydroxydaunorubicin (Adriamycin, Rubex)
Vincristine (Oncovin, Vincasar PFS)
Prednisone (Deltasone)
DHAP
Dexamethasone (Decadron)
Cytarabine (Cytosar, DepoCyt, Tarabine PFS)
Cisplatin (Platinol, Platinol-AQ)
Treatment of Non-Hodgkin Lymphoma
50
Part 2
Many of these regimens can also include the monoclonal antibody
rituximab (Rituxan) which is abbreviated by the letter R, usually at
the beginning or end of the regimen abbreviation (such as R-CHOP
or CHOP-R). Most of these chemotherapy drugs have been in
use for decades, but several have been developed more recently.
Bendamustine (Treanda) is a novel alkylating agent, a class of
drugs that cause damage to a cell’s DNA. Pralatrexate (Folotyn) is a
novel antimetabolite, a class of drugs that interfere with normal DNA
production. Since cancer cells divide more rapidly than normal cells,
they are more sensitive to DNA damage. Bendamustine was approved
in 2008 for the treatment of chronic lymphocytic leukemia and for
NHL that has progressed after treatment with a rituximab-containing
regimen. Pralatrexate was approved in 2009 for the treatment of
peripheral T-cell lymphoma that has progressed after prior treatment.
Both drugs are also being investigated for other uses.
EPOCH
Etoposide (VePesid, Etopophos, Toposar)
Prednisone (Deltasone)
Vincristine (Oncovin, Vincasar PFS)
Cyclophosphamide (Cytoxan)
Doxorubicin/hydroxydaunorubicin (Adriamycin, Rubex)
ESHAP
Etoposide (VePesid, Etopophos, Toposar)
Methylprednisolone (Solu-Medrol)
Cisplatin (Platinol, Platinol-AQ)
Cytarabine (Cytosar, DepoCyt, Tarabine PFS)
FC
Fludarabine (Fludara)
Cyclophosphamide (Cytoxan)
FND
Fludarabine (Fludara)
Mitoxantrone (Novantrone)
Dexamethasone (Decadron, Dexasone)
GDP
Gemcitabine (Gemzar)
Dexamethasone (Decadron, Dexasone)
Cisplatin (Platinol, Platinol-AQ)
GemOX
Gemcitabine (Gemzar)
Oxaliplatin (Eloxatin)
HyperCVAD/
MTX-Ara-C
Cyclophosphamide (Cytoxan)
Vincristine (Oncovin, Vincasar PFS)
Doxorubicin/hydroxydaunorubicin (Adriamycin, Rubex)
Dexamethasone (Decadron)
Methotrexate (Rheumatrex)
Cytarabine (Cytosar, DepoCyt, Tarabine PFS)
ICE
Ifosfamide (Ifex)
Carboplatin (Paraplatin)
Etoposide (VePesid, Etopophos, Toposar)
MINE
Mesna (Mesnex)
Ifosfamide (Ifex)
Mitoxantrone (Novantrone)
Etoposide (VePesid, Etopophos, Toposar)
P
Pralatrexate (Folotyn)
51
Understanding Non-Hodgkin Lymphoma
How is chemotherapy given?
Type of
Catheter
Description
Advantages
Disadvantages
A needle is used
to insert a small
flexible tube
(the catheter or
cannula) into a
vein in the hand
or arm. Drugs and
other fluids are
given through the
various types of
attachments.
No need for
surgical insertion.
A good option
for patients
who require few
infusions spaced
wide apart.
Sterile dressing needs
to be kept clean and dry
and replaced daily; the
line needs to be injected
periodically with a blood
thinner (heparin) to prevent
blockage.
To minimize the risk of
infections, the catheter
needs to be replaced
at least every 3 days
or sooner if it becomes
blocked.
Cannot be used to draw
blood for blood tests.
Hickman
Consists of 1-3
and Broviac tubes surgically
inserted through
the subclavian
vein (the vein that
runs underneath
the collar bone) in
the chest wall into
a vein. Six to 12
inches of tubing
remain outside
the skin.
It makes it easy
to draw blood and
give drugs using
standard needles
and without
having to pierce
the skin.
Requires proper care to
reduce the risk of infection
and blockage.
The tubes on the outside
of the body make it more
obvious that a catheter is
in place.
Patients need training and
instructions to learn to
clean and take care of the
external tubes.
Peripheral
Venous
Catheter
Treatment of Non-Hodgkin Lymphoma
52
Part 2
Depending on the regimen, patients will be given chemotherapy in pill
form, as an injection, or as an intravenous (IV) drip through a vein. To
make it easier to give and receive multiple cycles of chemotherapy by
IV, the doctor may insert an IV catheter or port that will stay in place
for a few weeks or for the duration of the chemotherapy treatment.
There are several types of these catheters, described in the following
chart. Patients should discuss with their doctor which catheter, if any,
would be best for their particular situation.
Infusaport
A catheter is
or Portacath surgically inserted
through the
subclavian vein
and attached to
a small reservoir
(port) that lies
under the skin.
Nothing is visible
on the outside
except for a bump
on the chest.
Patients do
not have to do
anything to care
for it; once a
month a nurse
keeps the line
open by “flushing”
with a small
amount of injected
liquid.
The patient must be
injected through the skin
with a special needle each
time it needs to be used.
Sometimes it is hard to use
it to draw blood samples
because of clogging (due to
a blood clot).
Peripherally
Inserted
Central
Catheter
(PICC line)
A good option
for patients
who only need
to have many
short infusions
or continuous
infusions given
in a hospital or
at home with a
portable pump.
This is more temporary than
the other types of catheters.
A thin, soft plastic
tube is inserted in
a large vein in the
arm.
Why is it important to adhere to the chemotherapy
treatment schedule?
Patients should adhere to the chemotherapy treatment schedule
because a full course of chemotherapy works best in the treatment of
their disease. In clinical studies, doctors have found that reducing the
dose or delaying chemotherapy may decrease the chance of a cure
or long-term survival for patients with certain types of lymphomas.
Changing the regimen to reduce short-term side effects may actually
be harmful in the long run. Some side effects may be unpleasant
but tolerable (see Part 3, “Side Effects and Living With Cancer”).
Other side effects may be serious but can often be anticipated and
prevented. It is very important that chemotherapy schedules be
maintained to the greatest extent possible.
What is radiation therapy?
Radiation therapy (also called radiotherapy) uses high-energy x-rays
or other types of radiation to kill cancer cells and shrink tumors. The
term is used typically to describe external radiotherapy, in which
53
Understanding Non-Hodgkin Lymphoma
radiation is delivered using an external radiation beam; however,
certain drugs can also deliver radioactive molecules directly to tumor
cells (see page 58, “What is radioimmunotherapy?”).
To prepare for radiation therapy, the healthcare team will precisely
mark the patient’s body with tiny ink dots (called tattoos) to make
sure that only the targeted areas receive radiation. During the day
of treatment, they will use lead shields to protect a patient’s normal
tissues around the radiation field. They use plastic forms, pillows, and
rolled blankets to make the patient comfortable and keep him or her in
the proper position. Patients need to lie still on a table beneath a large
machine that delivers the radiation painlessly. Once the preparations
have been made, it takes only a few minutes to deliver the prescribed
dose. The total dose of radiation is usually divided and given over 1-6
weeks. During and after the radiation treatment, patients will have to
carefully protect the radiation site from the sun.
Treatment of Non-Hodgkin Lymphoma
54
Part 2
A radiation oncologist will be in charge of your radiation therapy. The
part of the body selected to receive the radiation therapy is called
the radiation field. Doctors usually limit the radiation field to affected
lymph nodes, the areas immediately surrounding lymphoma nodes,
or other non-lymph node areas where the lymphoma started. Doctors
will decide on the type and size of the radiation field depending on the
type of tumor and the extent of disease.
Some of the more common types of radiation therapy and delivery
methods used for NHL include:
Electron Beam (EB)
Radiation
Intensity-Modulated
Radiation Therapy
(IMRT)
n
n
n
n
n
Total Skin Electron
Beam Radiation
Therapy (TSEBT)
n
n
Photopheresis or
Extracorporeal
Photochemotherapy
n
n
n
n
55
In this form of radiation therapy, a machine is used to
send electrons, or negatively charged particles, directly to
the area where the lymphoma is found and, potentially, to
nearby lymph nodes.
In this form of radiation therapy, different doses of
radiation are directed toward the cancer site using
radiation beams of varying intensities.
First, a 3-dimensional image of the tumor is collected
using CT, MRI, or PET scans.
Then, a special computer program analyzes the
3-dimensional image and designs radiation beams
specific to the shape of the tumor.
With this technique, doctors target the tumor with
radiation, while reducing exposure to the healthy tissue
surrounding it.
This is often used for the treatment of patients with
cutaneous T-cell lymphoma (CTCL), which is a form of
lymphoma that occurs on the outermost layers of skin.
TSEBT directs radiation to the entire surface of the body,
but because the radiation is weak it only penetrates the
outer layers of the skin. The deeper layers of skin and
other tissues are not exposed to radiation.
In this form of therapy, doctors remove a fraction of
the patient’s blood and treat it with a chemical that
makes lymphocytes more likely to die when exposed to
ultraviolet A light.
The blood is exposed to this ultraviolet light and reinfused back into the patient.
This form of therapy has been approved by the FDA for
the treatment of cutaneous T-cell lymphoma.
It may also be effective in the treatment of graft-versushost disease, a common complication following donor
stem cell transplantation.
Understanding Non-Hodgkin Lymphoma
Questions to Ask Before Starting
Radiation Therapy
n
What is the goal of my radiation therapy?
n
How will the radiation be given?
n
When will treatment begin? When will it end?
n
How will I feel during the therapy?
n
n
What are the side effects of radiation therapy? Is there anything
that can be done to prevent them?
Part 2
n
TIP
NT
PATIE
Are there any lasting effects?
What can I do to take care of myself during and after the
therapy?
n
How will we know if the radiation therapy is working?
n
How will the radiation treatment affect my normal activities?
What other types of drugs are used to treat patients with
non-Hodgkin lymphoma?
In addition to chemotherapy and radiation therapy, there are many
types of other drugs used to treat NHL. These include monoclonal
antibodies, immunoconjugates, radioimmunotherapy, fusion toxins,
proteasome inhibitors, and histone deacetylase (HDAC) inhibitors.
Most of these drugs have been developed relatively recently. Other
types of drugs may have been approved by the FDA since the time
this booklet was printed.
What are monoclonal antibodies?
As part of our immune system, specialized white blood cells called
plasma cells make proteins called antibodies. Antibodies help fight
infection by recognizing and sticking to anything that the body
considers “foreign.” Each antibody our body makes is naturally
designed to recognize one specific type of molecule.
Treatment of Non-Hodgkin Lymphoma
56
Monoclonal antibodies are molecules made in the laboratory that are
designed to recognize and stick to specific molecules on, for example,
cancer cells. When a monoclonal antibody attaches itself to a cancer
cell, it can stop or slow down its growth or it can make it easier for the
immune system to recognize it and kill it.
The monoclonal antibody rituximab (Rituxan) is approved by the FDA
to treat patients with NHL. The monoclonal antibodies alemtuzumab
(Campath) and ofatumumab (Arzerra) are approved by the FDA
to treat chronic lymphocytic leukemia (CLL). Monoclonal antibody
therapies are given to patients as intravenous infusions during visits
at the doctor’s office or clinic. See the following sections for additional
information about these monoclonal antibodies.
What is rituximab?
Rituximab (Rituxan) is a monoclonal antibody that recognizes CD20,
a specific molecule found on the surface of almost all B cells. In 1997,
rituximab became the first monoclonal antibody approved by the United
States Food and Drug Administration (FDA) for the treatment of patients
with cancer—specifically for the patients with relapsed or refractory lowgrade or follicular, B-cell NHL. As of 2012, rituximab is approved by the
FDA for the treatment of patients with NHL, including as maintenance
therapy following an initial response to rituximab, and for CLL in
combination with fludarabine and cyclophosphamide.
Rituximab treatment is given as an intravenous infusion; the schedule
varies depending on the type of combination regimen used. When
combined with chemotherapy, rituximab is usually given during the
first day of each chemotherapy cycle.
57
Understanding Non-Hodgkin Lymphoma
The side effects caused by rituximab are usually mild and include
chills, fever, nausea, rashes, fatigue, and headaches. Rarer more
serious side effects include trouble breathing and low blood pressure,
usually during the first infusion. Rituximab treatment can make a
person more susceptible to infection during and for up to 6 months
after treatment. Because of this, rituximab is not recommended for use
in patients with severe, active infections.
Alemtuzumab (Campath) is a monoclonal antibody targeting
CD52, a molecule found on the cell surface of many lymphoma
types. Alemtuzumab is approved specifically for treatment of CLL.
Alemtuzumab is given by intravenous infusion, initially at a low dose
every day and gradually increased in dose depending on how well it is
tolerated. Possible side effects are similar to those for rituximab.
What is ofatumumab?
Ofatumumab (Arzerra) is a monoclonal antibody that, like rituximab,
targets CD20. Ofatumumab is approved for patients with CLL who
are refractory to both fludarabine (Fludara) and alemtuzumab.
Ofatumumab is also administered by intravenous infusion every week
for 8 weeks followed by 4 additional doses every 4 weeks. Possible
side effects include many in common with other monoclonal antibodies.
What is radioimmunotherapy?
In radioimmunotherapy, a radioactive molecule is attached to a
monoclonal antibody to deliver small amounts of radiation therapy
directly to the cells that the monoclonal antibody recognizes. If you
are to be treated with radioimmunotherapy, your doctor will talk to you
about any necessary safety precautions.
While there are differences in scheduling, doses, and side effects,
patients treated with radioimmunotherapy usually have to undergo
imaging tests, 2-4 injections of the radioimmunotherapy drugs, and
close monitoring of blood counts for several weeks during and after
treatment.
Treatment of Non-Hodgkin Lymphoma
58
Part 2
What is alemtuzumab?
The radioimmunotherapeutic monoclonal antibodies ibritumomab
tiuxetan (Zevalin) and tositumomab (Bexxar) are used to treat patients
with indolent NHL. Similar to rituximab, both of these drugs target
CD20 expressing B cells.
Ibritumomab tiuxetan consists of the monoclonal antibody ibritumomab
linked to tiuxetan, a specialized molecule (called a chelator) that
is bound to the radioactive element yttrium-90. The ibritumomab
component of the drug specifically binds to NHL B cells that express
CD20. Once bound, the radioactive emissions from yttrium-90 damage
the cell, triggering its destruction.
Ibritumomab tiuxetan first received approval by the US FDA in 2002. It
is approved to treat patients with the following types of diseases:
n
n
Relapsed or refractory, low-grade, or follicular B-cell NHL.
Newly diagnosed follicular NHL who achieve partial or complete
response to first-line chemotherapy.
Ibritumomab tiuxetan is given through an intravenous injection in
combination with 2 rituximab treatments.
The most common toxicities associated with this treatment include low
blood cell counts, tiredness, stomach pain, nausea, inflammation of
the nose and upper throat, weakness, diarrhea, cough, and fever.
Tositumomab consists of a monoclonal antibody chemically linked with
the radioactive element iodine-131. Tositumomab also recognizes and
binds to CD20. This drug first received US FDA approval in 2003. It is
approved to treat patients with CD20-positive, relapsed or refractory,
low-grade, follicular, or transformed NHL (including patients whose
disease has not responded to rituximab treatment).
The most common toxicities associated with this treatment include low
blood cell counts, infections, infusion site reactions, weakness or lack
of energy, fever, and nausea.
59
Understanding Non-Hodgkin Lymphoma
What is brentuximab vedotin?
Brentuximab vedotin received approval by the FDA in 2011 for the
treatment of patients with the following:
n
n
Hodgkin lymphoma after failure of autologous stem cell transplant
or after failure of at least 2 previous combination chemotherapy
regimens in patients who are not candidates for autologous stem
cell transplant.
Systemic anaplastic large cell lymphoma after failure of at least 1
previous combination chemotherapy regimen.
Patients receive brentuximab vedotin as an intravenous infusion,
given once every 3 weeks. The most common side effects reported in
patients treated with this drug include a depressed immune system,
low blood counts, peripheral sensory neuropathy (a numbing of hands
or feet), fatigue, nausea, anemia, upper respiratory tract infection,
diarrhea, fever, rash, cough, and vomiting.
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Part 2
Brentuximab vedotin (Adcetris) is an immunoconjugate; it is a
combination of a monoclonal antibody against CD30 (brentuximab)
attached to the small toxic drug monomethyl auristatin E (vedotin or
MMAE). The monoclonal antibody part of this drug attaches itself to
lymphoma cells that express CD30, causing them to transport the drug
into the cells. Once inside cells, the MMAE drug is separated from
the antibody molecule. The MMAE attacks and breaks up an internal
support skeleton (called the microtubule network) of the cells, causing
them to stop dividing and die.
What is bortezomib?
Bortezomib (Velcade) is a proteasome inhibitor; these are a class of
drugs that inhibit the ability of cells to properly dispose of proteins.
Proteasome inhibition causes an abnormal build-up of proteins in
a cancerous cell, resulting in cell death. Bortezomib was the first
proteasome inhibitor developed, and was first approved in 2003 for
the treatment of multiple myeloma. Bortezomib was subsequently
approved in 2006 for the treatment of relapsed mantle cell lymphoma,
a type of NHL, and is being studied for other NHL types as well.
What are histone deacetylase inhibitors?
Histone deacetylase (HDAC) inhibitors are drugs that interact with
chromosomes in such a way to trigger the production of proteins
that normally would have been blocked by the cell. HDAC inhibitors
typically result in a cancer cell expressing proteins that interfere with
its ability to grow and survive.
Currently there are 2 HDAC inhibitors approved for the treatment of
NHL: romidepsin (Istodax), approved for the treatment of relapsed
cutaneous T-cell lymphoma and peripheral T-cell lymphoma, and
vorinostat (Zolinza), approved for the treatment of relapsed or
refractory cutaneous T-cell lymphoma.
What is maintenance therapy?
Maintenance therapy refers to the ongoing treatment of patients
whose disease has responded well to first-line treatment. The purpose
of maintenance therapy is to make it less likely that the cancer will
come back and to help to keep a more aggressive cancer that has
stopped growing from restarting to grow and spreading to other parts
of the body.
Maintenance therapy typically consists of drugs given at lower doses
and longer intervals than when they are given during initial therapy.
Depending on the type of NHL and the drugs used, maintenance
therapy may last for weeks, months, or even years. Common drugs for
use as maintenance therapy include rituximab, which is approved for
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Understanding Non-Hodgkin Lymphoma
NHL maintenance therapy following an initial response to rituximab,
and the immunomodulatory drug lenalidomide (Revlimid), which is
currently under investigation for NHL treatment (see Chapter 10,
“Advances in Treatment of Patients With Non-Hodgkin Lymphoma”).
Questions to Ask About Maintenance Therapy
Is maintenance therapy an option for me?
n
Why are you recommending maintenance therapy?
n
What are the benefits and risks?
n
How often and for how long will I receive this treatment?
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Does my insurance cover this treatment?
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Is this better for me than watchful waiting (checking for
recurrence, with no treatment)?
What are complementary and alternative remedies?
Alternative therapy refers to treatments that are used instead
of standard therapy recognized as effective by the medical
profession. Currently, there are no proven alternative therapies
to conventional cancer care for patients with NHL. Patients
should not use alternative remedies to replace the standard care
suggested by their doctors.
Complementary therapy is used in addition to standard medicine to
help improve a patient’s quality of life and to relieve the effects of
chemotherapy, radiation, and surgery. Patients should talk to their
doctor before starting any form of complementary therapy because
some of these practices can make cancer treatment less effective.
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Complementary therapy, also known as integrative medicine, includes
the following varied forms of therapy:
Mind/Body
Therapies
n
n
n
Touch
Therapies
n
n
n
Acupuncture
n
n
Nutrition
n
Examples: meditation, guided imagery, self-hypnosis, Tai Chi,
yoga.
Meditation, guided imagery, and self-hypnosis can help manage
stress.
Yoga and Tai Chi minimize stress and improve balance and
flexibility.
Examples: massage, reflexology (foot massage), Reiki, etc.
These techniques apply therapeutic pressure to the body to
restore a sense of harmony, relaxation, and well-being.
Studies suggest that massage may lessen pain.
Some studies show that acupuncture may relieve pain, nausea,
fatigue, hot flashes, and neuropathy (numbness and tingling in
the feet and hands) associated with chemotherapy and may help
decrease mild depression.
Using ultra-thin needles applied to specific points on the body,
acupuncture is safe and painless. Needles used should be
disposed of and only used once.
Patients undergoing lymphoma treatment should eat a healthy,
well-balanced diet that contains 5-7 servings of fruits and
vegetables a day, fish or poultry, and whole grains.
What is relapsed or refractory non-Hodgkin lymphoma?
Relapsed NHL means that the disease has returned after responding
to treatment—this is sometimes also called a recurrence. Refractory
NHL means that the patient’s disease no longer responds to a specific
treatment. There are many treatment options for patients with relapsed
or refractory lymphomas. Exactly what type of treatment is optimal
for individual patients with relapsed or refractory lymphoma depends
on factors such as the type of lymphoma, age, extent of disease,
overall health, and previous therapies received. Most combination
chemotherapies already discussed can be effective in patients
with relapsed or refractory lymphoma. Rituximab (Rituxan) may be
used in combination with many of these chemotherapy regimens.
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The radioimmunotherapy drugs ibritumomab tiuxetan (Zevalin)
and tositumomab (Bexxar) are also used in patients with relapsed
disease. Many centers will consider using autologous or allogeneic
transplantation for patients with relapsed or refractory NHL. Sequential
transplantations are possible if the disease continues to return or does
not fully respond.
Part 2
Patients who do not go into complete remission following treatment
or who do not respond to treatment should not lose hope. Complete
remission may be achieved following a diagnosis of relapsed or
refractory disease. Many patients seek second opinions at any point
from diagnosis onward and often choose to do so if their disease
relapses or is considered refractory.
Many of the novel therapeutic agents most recently approved by the
FDA and those being investigated in clinical trials are used specifically
for patients with relapsed or refractory disease. Lymphoma research
continually evolves as doctors and scientists discover new therapies
and more effective ways of giving existing treatments. Chapter 10
describes some of the options currently under investigation.
When should a clinical trial be considered?
Clinical trials are appropriate for patients at all stages of disease (see
Chapter 9, “Overview of Clinical Trials”). The purpose of a clinical trial
is to safely monitor the effects of a drug on patients over time and to
identify more effective therapies for specific diseases. By participating
in a clinical trial, patients may or may not get access to the newest
therapies but will receive quality care in a very carefully controlled and
supportive environment.
Participation in a clinical trial is especially important for patients with
NHL because many of the different lymphoma types are rare diseases,
which make it very hard to find enough patients to enroll in studies. If
patients are interested in participating in a clinical study, they should
ask their doctor if there is an appropriate trial for them and what the
potential risks and benefits may be.
Treatment of Non-Hodgkin Lymphoma
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What is stem cell transplantation?
There are different types of stem cell transplantation, depending on
who donates the stem cells. In an autologous stem cell transplant, the
patient is the donor. In an allogeneic stem cell transplant, the donor
is another person who is genetically similar to the patient—typically a
brother or sister, but the donor can also be an unrelated person.
The purpose of autologous or full-intensity allogeneic stem cell
transplantation is to allow patients to receive high-dose chemotherapy.
Such high doses effectively kill cancer cells but also severely damage
the bone marrow as a side effect, destroying the body’s source of
blood cells responsible for fighting infection, preventing bleeding, and
carrying oxygen. A stem cell transplantation re-populates the stem
cells responsible for making these blood cells.
Because high-dose therapy and stem cell transplantation place
great strain on a patient’s body, they are not options for everyone.
In deciding if transplantation is a good option, doctors will consider
the patient’s health status, age, medical history, cancer stage, and
response to previous therapy.
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ALLOGENEIC STEM CELL TRANSPLANTATION
Stem cell transplantation using stem cells from a donor who is
genetically similar to the patient.
2. Processing
Blood or
bone marrow
may be processed
in the laboratory
to purify and
concentrate the
stem cells.
Donor
3. Infusion
Stem cells
are infused
into the patient.
Part 2
1. Collection
Stem cells are
collected from
the donor’s bone
marrow or blood.
Patient
AUTOLOGOUS STEM CELL TRANSPLANTATION
Stem cell transplantation using a patient’s own stem cells.
1. Collection
Stem cells are
collected from the
patient’s bone
marrow or blood.
2. Processing
Blood or
bone marrow
may be processed
in the laboratory
to purify and
concentrate the
stem cells. Samples
are frozen until needed.
3. Reinfusion
Stem cells
are thawed and
reinfused
into the patient.
Patient
Treatment of Non-Hodgkin Lymphoma
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Reduced-intensity transplantation (also called non-myeloablative or
mini-allogeneic transplantation) uses lower doses of chemotherapy
and/or radiation prior to allogeneic transplantation. This option is
available only for allogeneic transplantation and cannot be used for
autologous transplantation. This approach takes advantage of the
graft-versus-disease effect, in which the transplanted cells (the “graft”)
recognize the cancerous cells in the patient’s body as foreign and
destroy them. Patients receiving reduced-intensity transplants may
avoid some of the side effects seen with higher-dose chemotherapy,
although they still have increased risks of serious side effects as
compared with autologous stem cell transplantation due to the
potential for graft-versus-host disease (in which immune cells in the
transplant recognize the patient cells as “foreign” and attack them).
Questions to Ask Before Deciding to Undergo
Stem Cell Transplantation
n
What type of transplantation is most appropriate for me?
n
Why do you think this is a good idea?
n
What are the risks associated with this procedure?
n
Why do you recommend this particular type of transplantation?
n
If I need a donor, how will I find one?
n
How long will I need to be in the hospital?
n
What type of special care will I receive?
n
How sick will this treatment make me?
n
What will you do to lessen the side effects?
n
How will we know if the treatment is working?
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How and for how long will the treatment affect my normal
activities?
What is my chance of making a full recovery?
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For more information on transplantation, please visit the “Be the
Match” website at www.bethematch.org.
Drug costs: What to do if insurance will not pay
Patients in need of financial assistance should talk with their doctor
and social worker about available options and how to enroll in an
appropriate program. Before undergoing a medical procedure, patients
should check with their insurance carrier to ensure that it is covered.
If there is a dispute about coverage or if coverage is denied, patients
should ask their insurance carrier about its appeals process. Contact
your state’s department of insurance if a claim is denied.
Treatment of Non-Hodgkin Lymphoma
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Part 2
Many patients today face the problem of how to pay for rising
healthcare costs. Cancer organizations like the Lymphoma Research
Foundation (www.lymphoma.org) offer limited financial assistance to
patients who qualify. Most pharmaceutical/biotechnology companies
have patient assistance programs in place that provide drugs for free
to qualifying patients.
Part 3 — Side Effects and Living With Cancer
Chapter 7: Common Treatment Side Effects
Patients with NHL may experience various side effects or toxicities
caused by their cancer treatment. Fortunately, medications and
lifestyle changes can effectively prevent or lessen the severities of
most of these side effects. Patients should ask their healthcare team
about possible treatment side effects and how to prevent and manage
them and tell their doctor or nurse if they experience any side effects.
This chapter explains the causes of these side effects, the types
of side effects caused by different treatments, and steps to take to
minimize these side effects.
Why does chemotherapy cause side effects or toxicities?
Chemotherapy drugs cause side effects because of the non-specific
way these drugs attack cancer cells. Most chemotherapy drugs are
designed to kill cells like cancer cells that divide rapidly (meaning that
they are multiplying quickly). Most normal cells in the body do not
divide as quickly as cancer cells. However, healthy cells in hair roots,
and cells in the mouth, gastrointestinal tract, and the bone marrow do
divide rapidly and can be killed or damaged by chemotherapy. Some
chemotherapy drugs can also damage heart or lung cells.
The type and severity of side effects caused by chemotherapy
vary widely depending on the types of drugs that are given and an
individual patient’s response. The same drug may cause no side
effects in one patient, while in others it may cause anything from very
mild to very serious side effects.
What is the difference between long-term effects and late
effects?
Long-term effects are toxicities that happen during cancer treatment
and continue for months or several years. Fatigue, menopausal
symptoms, infertility, and lung problems are examples of long-term
effects.
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Late effects of treatment become apparent only after treatment has
ended and may arise many months, years, or even decades after
treatment is completed. Cardiovascular problems, osteoporosis, and
secondary cancers (such as lung cancer) are examples of late effects.
The combination of the chemotherapy drug doxorubicin (Adriamycin)
and radiation, especially when the radiation is directed to the chest
area, can lead to late effects to the heart, causing a decrease in
cardiac function and accelerated atherosclerosis in which plaque
builds up on the inside of the arteries.
What side effects are caused by chemotherapy?
Part 3
Note that side effects vary depending on the type of chemotherapy;
additionally, these adverse effects can have causes other than
chemotherapy.
Some of the most common side effects include:
n
Changes in taste.
n
Decreased blood cell production.
n
Increased chance of infections.
n
Fatigue.
n
Hair loss.
n
Loss of appetite.
n
Mouth sores.
n
Nausea and vomiting.
n
Problems with sexual function.
n
Cognitive problems (trouble concentrating, impaired memory).
n
Peripheral neuropathy.
Side Effects and Living With Cancer
70
Changes in taste
Some patients will experience a change in the way foods or beverages
taste. Familiar foods may taste differently (dysgeusia) or the flavors of
foods may not be as strong (hypogeusia). Some patients may also feel
that foods have a metallic taste. These side effects are temporary and
usually disappear after the end of chemotherapy.
Decreased blood cell production
The bone marrow constantly produces red blood cells, white blood
cells, and platelets. Some types of chemotherapy and immunotherapy
temporarily interfere with the ability of the bone marrow to produce
enough of 1 or more of these different types of blood cells. This is
called myelosuppression.
To prevent and control myelosuppression, samples of a patient’s blood
are tested for: complete blood count (CBC), which measures the
number of red blood cells; differential, which measures the amounts
of different types of white blood cells; and the number of platelets.
These tests are usually done before and sometimes during each
chemotherapy cycle.
There are 3 main conditions caused by decreased production of blood
cells:
Anemia
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This is caused by a decrease in the number of red blood
cells.
Many chemotherapy drugs cause mild or moderate
anemia.
Anemia can make people feel very tired and short of
breath; if needed, anemia can be treated with drugs or
red blood cell transfusions.
Understanding Non-Hodgkin Lymphoma
Neutropenia
n
n
n
n
Thrombocytopenia
n
n
n
Patients with low neutrophil count are at risk of serious
and even life-threatening infections—symptoms of
infection include fever, chills, and night sweats.
A normal white blood cell count ranges from 4,000-10,000
cells per microliter. Doctors regularly monitor the absolute
neutrophil count (ANC), the number of neutrophils in the
peripheral blood. Because patients with an ANC below
500 are at high risk for infections, their doctors may
decrease the chemotherapy dosage or delay the next
treatment in order to keep the ANC above 500.
Some patients require treatment with antibiotics and
hospitalization to prevent or treat infections.
Part 3
n
Neutropenia refers to a decrease in neutrophils—the
primary type of white blood cells that fight infection.
To avoid a patient missing a dose of chemotherapy,
doctors sometimes prescribe drugs like filgrastim
(Neupogen) and pegfilgrastim (Neulasta) to reduce the
duration and severity of neutropenia. These drugs can
sometimes cause bone pain which can be relieved with
nonsteroidal anti-inflammatory drugs (NSAIDs) such as
aspirin and ibuprofen.
Thrombocytopenia refers to a decrease in the number
of platelets in the blood; platelets help start the clotting
process when bleeding occurs.
Patients with low platelet counts may bruise easily; have
cuts that bleed for too long or too much; have nose
bleeds or bleeding gums; or may bleed from places that
have not been injured.
Some patients require a platelet transfusion to stop or
prevent bleeding.
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Reducing Your Risk of Serious Infection
During Chemotherapy
n
n
If you have a fever of 100.5°F or greater, call your doctor or go
to the emergency room.
Ask your doctor what you should do if you have a sore throat,
rash, diarrhea, a cough, or redness, swelling, or pain around a
wound.
Fatigue
Fatigue is a common side effect of many types of chemotherapy.
Fatigue should decrease after patients have completed their
lymphoma treatment, but it could take weeks or months until they
return to their normal energy levels.
Coping With Fatigue
n
n
n
n
73
Keep a diary to help you keep track of when you have the most
energy and which activities make you feel tired or give you
energy. Use this information to plan your activities for the times
when you have the most energy.
Ask for help.
Exercise if your doctor says it is okay to do so, but do not
overdo it. Try simple stretching and range-of-motion exercises
or a short walk; these may energize you without tiring you out.
Start slowly and build up to the level that is right for you. Ask
your doctor, nurse, or physical therapist to help you create a
personal exercise plan.
Rest and sleep during therapy are very important, but do not
rest more than you need because it may decrease your energy
levels. An afternoon nap helps many patients feel less tired for
the rest of the day. Other patients cannot sleep at night if they
nap during the day. If you have trouble sleeping, talk to your
healthcare team to find out why and what you can do about it.
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Hair loss
Certain chemotherapy drugs can cause thinning or loss of hair
(alopecia) anywhere in the body, including the scalp, eyebrows,
eyelashes, arms, legs, and pelvis. The amount of hair loss may vary.
If hair loss occurs, it often starts 2 or 3 weeks after the first
chemotherapy treatment. Remember that hair loss caused by
chemotherapy is usually temporary. Hair will probably grow back
after the end of chemotherapy treatments. When the hair first grows
back, it may have a slightly different texture or color than it had before
treatment. Over time, the texture and color often return to normal.
n
After washing it, pat your hair dry instead of rubbing it with a
towel.
n
Brush your hair with a soft-bristle brush or a wide-tooth comb.
n
Do not use curlers and hair dryers.
n
Do not color or perm your hair, or treat it with other chemicals.
n
n
Consider using a wig, scarf, turban, soft cotton hat, or head
wrap. Some health insurance companies cover the cost of
wigs if you have a doctor’s prescription. Check your policy to
see if it covers this cost.
Use a hat or scarf to protect your scalp when you are out in
the sun.
Side Effects and Living With Cancer
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Part 3
Managing Chemotherapy-Induced Hair Loss
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Mouth sores
Some chemotherapy drugs can make a patient’s mouth become red,
sore, or irritated—this is called mucositis. Some patients undergoing
chemotherapy become more susceptible to viral or fungal infections of
the mouth and throat.
Patients should tell their doctor if they have a sore throat. The doctor
will examine the patient’s throat and may take a swab to send to the
lab to check for infection. Several medications are available to treat
different types of infections. To help decrease chances of infection,
patients should have a complete dental checkup and cleaning before
starting chemotherapy.
Preventing and Caring for Mouth Sores
n
n
n
n
n
n
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Clean your mouth and teeth. Use a soft-bristle toothbrush,
nonabrasive toothpaste, and lip moisturizer.
Do not use mouthwashes that contain alcohol. Your doctor or
nurse may recommend a mouth rinse.
Do not eat citrus fruits (such as oranges, grapefruit, lemons, or
clementines) or drink citrus juices.
Do not eat spicy foods.
Eat soft foods while you are taking chemotherapy to avoid
bruising your gums and other soft tissues in your mouth.
Do not floss your teeth if your blood counts are low.
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Nausea or vomiting
Some chemotherapy drugs can cause nausea or vomiting, usually
on the day chemotherapy is administered but sometimes 1 or 2
days later. Your doctor may prescribe a drug that prevents vomiting
(antiemetic) before chemotherapy. Examples of antiemetics include:
aprepitant (Emend), ondansetron (Zofran), granisetron (Kytril),
metoclopramide (Reglan), prochlorperazine (Compazine), and
dolasetron (Anzemet), and a variety of corticosteroids, such as
prednisone (Deltasone). In most cases, these antiemetics are able to
partially or completely prevent nausea and vomiting.
n
n
n
n
n
n
Part 3
Controlling or Minimizing
Nausea and Vomiting
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Before chemotherapy, drink a liquid diet, such as broth,
consommé, or water. Do not drink milk.
Do not eat foods that are too hot, cold, sweet, or spicy.
Eat smaller and more frequent meals instead of fewer large
meals each day.
Avoid strong or offensive smells. Get plenty of fresh air.
Take prescribed antiemetics before chemotherapy to prevent
nausea.
If you vomit, make sure to avoid becoming dehydrated.
Side Effects and Living With Cancer
76
Diarrhea
Some types of chemotherapy cause diarrhea. While most patients do
not experience severe diarrhea, the most important thing to remember
is to avoid dehydration, a loss of body fluids. Call your doctor if you
have bloody diarrhea or fever with diarrhea.
Avoiding Dehydration
From Diarrhea or Vomiting
n
n
n
n
n
n
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Drink plenty of liquids (8 glasses a day) such as water or
electrolyte replacement drinks like Gatorade and Powerade.
Look for the following signs of dehydration: dry mouth or skin,
decreased urine, or feeling dizzy or lightheaded when you stand
up.
Do not drink or eat milk products because they worsen diarrhea.
Do not eat high fiber and other hard to digest foods because
they can worsen diarrhea.
Eat plenty of bananas and other high-potassium food (check
with your doctor or dietitian to make sure that these foods will
not interfere with your chemotherapy or other medications that
you are taking).
Take the medicines that your doctor recommends to control
diarrhea or vomiting (call your doctor if symptoms persist).
Problems with sexual function
Chemotherapy can cause a drop in the sex drive (libido). Usually, a
normal libido returns after treatment is finished. Patients should not be
embarrassed to talk with their doctor about any problems or concerns
they have about changes in their libido.
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Sterility
Since chemotherapy and radiation may damage sperm and egg
cells, it can sometimes cause temporary or permanent sterility, or
the inability to have children, in both men and women. The potential
for developing sterility depends on the treatment type and specific
dose, the number of therapies given, and the patient’s age at the
time of treatment. Patients should speak with their doctor about
fertility preservation (such as treatments to protect the ovaries
or cryopreservation of sperm cells, egg cells, or in vitro-fertilized
embryos) before starting treatment. For more information and
resources about sterility, visit the website for Fertile Hope at
www.fertilehope.org.
Chemotherapy can result in mild cognitive impairment such as trouble
concentrating, impaired memory, or issues with motor control. While
such symptoms can be distressful, they typically disappear over time.
Peripheral neuropathy
Some chemotherapy drugs may also cause damage to the nervous
system called peripheral neuropathy. Nerve damage can cause side
effects such as constipation or a tingling sensation in the fingers and
toes.
Cardiotoxicity
Cardiotoxicity refers to damage to cells in the heart or heart muscle.
Long-term use of certain chemotherapy drugs can cause heart
damage in some patients. Doxorubicin is an example of a drug that is
possibly cardiotoxic.
In general, most patients with NHL treated with potentially cardiotoxic
chemotherapy receive these drugs at dose levels and numbers of
cycles where cardiac toxicity is usually not a problem. For example,
many patients with diffuse large B-cell lymphoma only need to be
treated with chemotherapy once; therefore, their risk for developing
chemotherapy-related cardiovascular disease is small.
Side Effects and Living With Cancer
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Part 3
Cognitive problems
A person’s history of heart disease, high cholesterol and high blood
pressure, and obesity and lifestyle choices such as smoking and lack
of exercise may increase their chance of developing chemotherapyrelated or radiation-related cardiotoxicity.
Careful monitoring by the patient’s healthcare team can reduce
the chances of developing cardiotoxicity. Before deciding to treat
patients with a cardiotoxic drug, most doctors will prescribe either an
echocardiogram or a MUGA (multi-gated acquisition) scan to measure
their cardiac function. This will ensure that the chemotherapy dose is
well within the range considered safe for the heart.
Lung toxicity
Damage to the lungs is a serious side effect that can be caused by
bleomycin-containing chemotherapy regimens. Patients should report
any changes in lung function such as cough, chest pain, or shortness
of breath to their doctor, who may decide to monitor their lung health
by regularly performing pulmonary function studies during the course
of chemotherapy.
Other possible side effects
Chemotherapy can also cause other side effects such as cough,
skin rashes, general weakness, sore throat, and loss of balance
or coordination. Patients are sometimes at increased risk for viral
infections, particularly shingles (herpes zoster). Many of these side
effects are temporary, but some could last for an extended period.
Patients should call their doctor if they experience any painful local
rash with or without blisters.
What side effects are caused by radiation therapy?
Radiation therapy itself is painless, but it can cause short-term and
long-term side effects. The side effects caused by radiation therapy
vary depending on the type of radiation, the radiation dose, and the
part of the body treated. Side effects are usually worse when radiation
therapy and chemotherapy are given at the same time.
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Examples of Potential Short-Term
Side Effects of Radiation Therapy
n
n
n
n
n
Radiation to the stomach area can cause nausea, vomiting, and
diarrhea.
Radiation to the chest and neck can cause a dry sore throat,
mouth sores, and trouble swallowing.
Radiation to any area may cause hair loss in the area and the
skin may become red, dry, and tender.
Radiation to the pelvis, legs, and torso (the large areas of your
body that contain most of your blood-producing bone marrow)
can decrease levels of red blood cells and white blood cells.
Examples of Potential Long-Term
Side Effects of Radiation Therapy
n
n
n
n
n
n
The development of new cancers in the radiated parts of the
body.
Cardiovascular damage causing an increased risk of heart
attack and stroke.
Lung damage and problems breathing due to radiation to the
chest.
Thyroid problems (such as fatigue and weight) later in life due
to radiation to the neck.
Headaches, memory loss, personality changes, and trouble
concentrating due to radiation to the brain.
Neck muscle weakness (“neck drop”) causing difficulty lifting
the head, and neck pain or discomfort.
Dry mouth
Some patients treated with radiation therapy experience a temporary
decrease in saliva production, or dry mouth (xerostomia). People with
dry mouth may have problems swallowing foods or thick liquids. Dry
mouth can also cause food particles to stick to the teeth and gums.
Because saliva helps prevent cavities, doctors may advise patients
to go to the dentist for fluoride treatments before they start radiation
therapy.
Side Effects and Living With Cancer 80
Part 3
Radiation to any part of the body may cause fatigue, which may
progressively worsen during the later weeks of the treatment
cycle.
Fatigue
The likelihood that patients will experience fatigue depends on their
disease and the specific radiation plan.
Loss of appetite and taste
During radiation treatment, patients might lose their appetite for foods
that they normally like. The loss of appetite and taste are usually
short-term problems. Patients should remember to eat well because
their body needs energy and good nutrition to heal. Eating 4 or 5 small
meals a day may be more comfortable than eating 2 or 3 larger ones.
Patients should ask their healthcare team for information on how to
maintain good nutrition during treatment.
Nausea
Radiation treatment can cause nausea, especially in patients who
have radiation to the abdomen. Not eating (especially sweet, spicy,
or fatty foods) a few hours before radiation therapy may help avoid
nausea. A patient’s doctor may prescribe an anti-nausea (antiemetic)
medication to be taken before each radiation therapy session.
Skin reactions
Radiation therapy can cause skin changes to the affected area such
as redness, itchiness, dry and peeling skin, sores or ulcers, swelling,
and puffiness. These skin changes usually decrease and disappear
over a few weeks after the radiation therapy ends. Some skin changes
may last much longer or be permanent. These changes include:
darker and blotchy skin, very dry, or thicker skin. The radiated area
will sunburn more easily than other parts of your body. Make sure to
avoid tanning beds and protect yourself from the sun with a hat, long
sleeves, long pants, and sunscreen with an SPF of at least 30.
Talk to your doctor or nurse if you notice any skin changes.
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Understanding Non-Hodgkin Lymphoma
Skin Care During and After Radiation Therapy
n
n
n
n
n
n
n
n
n
n
n
n
Use lotions and other skin products that your doctor prescribes
or your nurse suggests.
Do not put anything on your skin that is very hot or cold (such
as heating pads or ice packs).
Take a shower or bathe in lukewarm water; if you bathe, do it
every other day and soak for less than 30 minutes; always use
a mild unscented soap; pat dry your skin; do not wash off the
ink markings needed for radiation therapy.
Check with your doctor or nurse before using bubble bath,
cornstarch, cream, deodorant, hair removers, makeup, oil,
ointment, perfume, powder, and sunscreen.
Part 3
n
Be gentle with your skin; do not rub, scrub, or scratch.
TIP
NT
PATIE
Wear soft clothes and use soft sheets, such as those made with
cotton.
Do not wear clothes that are tight and do not allow your skin to
breathe.
Make your rooms more humid by placing a bowl of water on the
radiator or using a properly cleaned and maintained humidifier.
Do not sunbathe; protect your skin from the sun every day (use
a broad-rimmed hat, long-sleeved shirt, and long pants or skirt
outside).
Do not use tanning beds.
Do not put adhesive tape or bandages on your skin. Ask your
nurse about ways to bandage without tape.
Ask your doctor or nurse if it is okay to shave the affected area;
shave with an electric razor and do not use pre-shave lotion.
Report to your doctor or nurse any skin changes you notice.
Side Effects and Living With Cancer
82
Throat irritation
Radiation therapy to the neck, throat, or chest may cause sore throat,
dry mouth, nausea, or cough. Patients may have difficulty eating or
swallowing, especially toward the end of their treatment regimen.
Patients should tell their doctor if they have problems swallowing.
There are treatments for the discomfort. Difficulty swallowing will
usually go away after a few weeks of treatment.
Easing Throat Irritation
During Radiation Therapy
n
n
n
n
TIP
NT
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Eat bland foods that are soft, smooth, and easy to digest,
such as pudding, yogurt, milk shakes, and commercial dietary
supplements.
Take small bites and swallow each bite completely before taking
another.
Try drinking thicker liquids, such as fruit that has been pureed in
a blender; they are easier to swallow than thin liquids.
Avoid citrus fruits, especially juices.
What side effects are caused by steroids?
Cortisone, dexamethasone, prednisone, and other corticosteroid drugs
can cause side effects such as insomnia (the inability to fall asleep),
increased appetite, mood or personality changes, high blood pressure,
and weight gain.
Prednisone can also trigger diabetes in patients prone to that disease
or make diabetes worse in patients who already have the disease.
High doses of steroids can also cause osteoporosis in at-risk
patients. Patients should tell their family and friends that personality
changes may occur during treatment. Patients should avoid making
hasty decisions. If personality changes occur, the doctor should be
informed—the dose may need to be reduced.
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Understanding Non-Hodgkin Lymphoma
What side effects are caused by rituximab and other
antibody (or biologic) therapies?
Although side effects caused by biologic therapies vary according
to the specific type of treatment, they usually occur during treatment
administration and may include flu-like symptoms such as chills, fever,
muscle aches, weakness, loss of appetite, nausea, vomiting, and
diarrhea.
Rituximab (Rituxan) may reduce immunoglobulin levels, especially
when given as maintenance therapy. The decrease in immunoglobulin
levels can lead to infections (especially sinusitis and upper respiratory
infections) which sometimes require treatment with intravenous
gammaglobulin.
Patients treated with high doses of chemotherapy and/or radiation
before undergoing a stem cell transplant are at increased risk for
developing infection, bleeding, and other side effects as described
perviously (see, “What side effects are caused by chemotherapy?” and
“What side effects are caused by radiation therapy?”).
Patients receiving high-dose chemotherapy with autologous stem cell
support (autologous stem cell transplantation) are followed carefully
for the first 3-4 weeks because of the risks of mouth sores (mucositis),
infection, anemia (low red blood cell count causing fatigue), and
bleeding. Transfusions and antibiotics, often in the hospital, may be
necessary.
Patients receiving stem cells from a sibling or unrelated donor are also
at risk of developing graft-versus-host disease (GVHD), a condition
where the donated marrow’s immune system attacks the patient’s
tissues. GVHD can happen at any time after the transplant. Drugs can
be used to reduce the risk of developing GVHD or to treat the problem
once it develops.
Side Effects and Living With Cancer
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Part 3
What side effects are caused by stem cell transplantation?
More information about stem cell transplantation and its effects can be
found at www.bethematch.org.
When should a patient’s doctor be called?
As a general rule:
n
n
n
85
Call if the patient experiences a side effect that is unexpected or
lasts longer than expected.
Call if the patient experiences a medical problem—such as high
fever, shortness of breath, prolonged or constant nausea and
vomiting, chest pains, and dizziness—that cannot wait for a regularly
scheduled appointment.
If the patient’s doctor or nurse cannot be reached, go to the hospital
emergency room for a medical assessment and place another call to
the doctor.
Understanding Non-Hodgkin Lymphoma
Part 3 — Side Effects and Living With Cancer
Chapter 8: Managing Your Life During and After Treatment
This chapter talks about some general issues that patients may
encounter while they live their life during and after treatment.
Coping strategies
Each person’s experience with cancer is different, and how he or she
copes with the physical and emotional impact of having NHL is unique
to a patient’s personality and situation. Here are some suggestions for
how to cope with some issues that patients may face.
■
■
■
■
Get Help
for
Depression
■
■
■
■
Deal with
Physical
Changes
■
■
■
■
Maintain
a Healthy
Lifestyle
Set
Reasonable
Goals
■
■
■
■
■
■
Communicate your fears and concerns about your disease by talking with your family,
friends, doctors, and counselors.
Writing down your concerns in a journal may also help.
Find a support group or other individuals who are also coping with cancer.
Feeling sad or depressed is not unusual in people living with cancer.
Watch out for signs of depression: sleeping more or less than usual; feeling a lack of
energy; crying; inability to concentrate.
Ask for a referral to a psychiatrist, social worker, psychologist, or counselor who will
help you cope with your feelings through talk therapy, medications, or both.
Find a support group of people who have had similar experiences.
Some patients with cancer feel unattractive because of hair loss and other changes in
appearance caused by their treatment.
Ask your doctor what changes you should expect; plan ahead and buy a wig or head
covering if hair loss is a possibility.
Get advice from a beautician about makeup for the areas that you consider a problem.
Ask your healthcare team for advice on how to manage temporary changes such as
dry skin, brittle nails, and a blotchy complexion.
Eat a healthy diet that includes fruits, vegetables, protein, and whole grain.
Engage in regular physical exercise; this can reduce anxiety, depression, and fatigue,
and improve mood.
Get sufficient rest to help combat the stress and fatigue of your disease and its
treatment.
Quit smoking and reduce alcohol consumption.
Having goals for how you want to live your life during and after treatment will help you
maintain a sense of purpose.
Avoid setting unreasonable goals, such as deciding to work full-time while part-time
would be much better for your health.
Stay as active and involved as you can in work and other activities that interest you.
Side Effects and Living With Cancer
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Part 3
Maintain
a Strong
Support
System
The importance of pain control
Patients may feel pain from the cancer itself or from treatments and
procedures. Cancer pain is very treatable and there is no reason for
a patient to tough it out without help. Patients should tell their doctors
and nurses if they have any pain because doctors and nurses can
offer advice regarding medications and other ways to relieve the pain.
Different types of pain are best controlled by different types of pain
relievers:
n
n
n
n
n
n
87
Mild to moderate pain can be treated with acetaminophen and
nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and
ibuprofen.
Moderate to severe pain is best controlled with opioids such as
morphine, hydromorphone, oxycodone, and hydrocodone.
Tingling and burning pain can be controlled with anti-depressants
and anti-epileptics.
Pain caused by swelling can be controlled by steroids such as
prednisone and dexamethasone.
Non-drug pain treatments include: biofeedback, breathing and
relaxation exercises, distraction, heat or cold packs (avoid these
following radiation therapy), hypnosis, imagery, massage, pressure
and vibration, and transcutaneous electrical nerve stimulation
(TENS).
If the pain is not relieved by medicines and non-drug pain
management, the following treatments can also be used to relieve
the source of the pain: radiation therapy, nerve blocks/implanted
pump, neurosurgery, and surgery.
Understanding Non-Hodgkin Lymphoma
Managing Pain
n
Tell your doctor or nurse about your pain. Be specific when you
describe it.
TIP
NT
PATIE
– Where do you feel the pain?
– What type of pain is it (sharp, dull, throbbing)?
– Does it come and go, or is it steady?
– How strong is it? How long does it last?
– Does anything make the pain feel better or worse?
– Which drugs have you taken for the pain? Do they help? If so,
for how long?
n
n
n
n
Take your pain medication on a regular schedule even if the
pain seems to be better. Do not skip doses.
Part 3
n
Tell your family and friends about your pain so that they can
help you and so that they can understand why you may be
acting differently.
Try deep breathing, yoga, or other ways to relax.
Ask to meet with a pain specialist or palliative care specialist to
help you find better ways to control your pain.
Tell your doctor or nurse of any changes in your pain.
Maintain a healthy lifestyle
Regular physical activity helps keep the cardiovascular system strong
and body muscles flexible. Exercise can also help alleviate breathing
problems, constipation, and mild depression. It also helps reduce
stress and fatigue. Patients should talk to their doctor before starting
an exercise program.
Side Effects and Living With Cancer
88
Several types of exercise are particularly helpful:
n
n
n
n
General physical activity, such as swimming, dancing, household
chores, and yard work.
Aerobic activity to improve cardiovascular fitness, such as walking,
jogging, and bicycling.
Resistance training to strengthen muscles, protect joints, and help
remedy osteoporosis by building bone mass.
Flexibility exercises such as stretching and yoga to improve range of
motion, balance, and stability.
Eating a healthy diet is especially important during treatment for NHL
because it will help patients keep up their strength and energy, tolerate
treatment-related side effects, decrease their risk of infection, and
heal and recover more quickly. Patients should aim for a diet high
in fruits and vegetables, protein (poultry, fish, and eggs), and whole
grains. During chemotherapy and after a stem cell transplant, a patient
may temporarily be asked to avoid raw fruits and vegetables that
may increase the risk of infection if you have a low white blood cell
count (“neutropenic diet”). A patient’s healthcare team can help put
together an eating plan that is appropriate. Patients should talk to their
doctor before taking any dietary supplements such as multivitamins
or individual vitamin supplements, as well as any herbal or “natural”
supplements, because they may interfere with treatments or have
unexpected side effects.
The importance of follow-up care
At the first visit following the completion of treatment, patients should
talk to their doctor about their follow-up schedule. This will be different
from patient to patient depending on their disease type, age, and
general health. Patients should adhere to their schedule of follow-up
visits—these are very important for monitoring disease recurrence
and detecting and treating any health problems that might have been
caused by the treatment.
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Understanding Non-Hodgkin Lymphoma
During these follow-up visits, the doctor will ask about any medical
changes since the last appointment and give a physical examination;
the doctor may also prescribe imaging, blood, molecular diagnostic, or
other laboratory tests.
Be proactive in healthcare decisions
To stay proactive in healthcare decisions, patients should get the
following information from their medical team:
n
n
Copies of their medical records and a written summary of their
treatment in case they switch oncologists or need to see a primary
care physician for routine medical care.
A list of signs of disease recurrence and late side effects from
treatment.
n
Any new symptoms.
n
Pain.
n
n
Physical problems that disrupt their daily life such as fatigue,
insomnia, sexual dysfunction, and weight gain or loss.
Any new health problems, such as heart disease, diabetes, and high
blood pressure.
n
Any new medications and vitamins they are taking.
n
Emotional problems such as anxiety and depression.
n
Any other questions or concerns.
Side Effects and Living With Cancer
90
Part 3
At the follow-up care appointments, patients should be sure to tell their
doctor about:
Part 4 — Clinical Trials
and Advances in Treatment
Chapter 9: Overview of Clinical Trials
There are hundreds of NHL clinical trials now underway in hospitals,
cancer centers, and doctors’ offices around the country. The
government, pharmaceutical and biotechnology companies, universities,
and doctor groups often sponsor clinical trials. The United States Food
and Drug Administration (FDA) and the institutional review board (IRB)
of participating hospitals or institutions must approve all clinical trials.
What is a clinical trial?
A clinical trial is a carefully designed research study that involves
people who volunteer to participate. Clinical trials are also sometimes
referred to as clinical studies. However, the term “clinical study” is
broadly used to describe many different sorts of studies in addition to
those described in this chapter.
The purpose of clinical trials in cancer is to answer questions about
new ways to treat, diagnose, prevent, or manage a disease or the side
effects caused by treatments. Strict rules and oversight procedures
make sure that clinical trials are designed and run in a way that protects
the rights and safety of the people who volunteer to participate.
In the United States, a new drug must pass through a strict approval
process governed by the FDA before it can become a standard
therapy for use in people. The FDA-regulated approval process for
drugs includes preclinical studies (done in laboratories) and clinical
trials (done in hospitals and clinics).
As shown in the following table, there are 4 main types (or phases)
of clinical trials. The first 3 are usually required before a drug is
considered for approval by the FDA. Phase IV studies are performed
after a drug has received FDA approval; these trials are sometimes
called post-marketing studies. Patients may be eligible to take part in
different types of clinical trials depending on their health status, type
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Understanding Non-Hodgkin Lymphoma
and stage of lymphoma, and type of treatment, if any, they previously
received.
Phase
Description
Phase I
n
To find a safe dose.
n
To decide on a treatment regimen.
n
Phase II
n
n
Phase III
n
n
n
n
15-30 people with one or
more different types of
cancer.
To see if the treatment causes
any side effects.
To find out if a new treatment has
an effect against a certain type of
cancer.
n
Usually fewer than 100
people with the same type of
cancer.
To see if the treatment causes any
side effects.
To compare new treatments or
new uses of existing treatments
with current standard treatments.
The main things being compared
usually are how well the treatment
works and what type of side
effects it causes.
To get more information about the
long-term safety and effectiveness
of a new treatment.
n
n
n
From 100 to several
thousand people with the
same type of cancer.
Patients are randomly
assigned to a treatment
group; one group receives
the standard therapy and
the other group receives the
experimental treatment.
Several hundred to several
thousand people with the
same type of cancer.
Why is a placebo sometimes used in phase III trials?
A placebo is an inactive ingredient that is used as a comparator in
some clinical trials. In such trials neither the patients nor the doctors
and nurses treating them will know which patients receive a placebo
versus the experimental drug.
In cancer clinical trials, patients are never given a placebo in
place of an effective standard therapy. They would be given a
placebo only if there were no standard therapies to compare against.
Placebo-controlled trials are never done in a manner to deny patients
an effective therapy.
Clinical Trials and Advances in Treatment 92
Part 4
Phase IV
Number of Volunteer Patients
Should I participate in a clinical trial?
Clinical trials are not a last resort for patients. Patients with all stages
of NHL can often benefit from participation in clinical trials, whether at
the time of initial diagnosis or at relapse. Clinical trials offer patients
therapies that are not otherwise available to all patients. Another
advantage of clinical trials is that the health of enrolled patients is
monitored very carefully. In many cases, patients can benefit more
from participation in clinical trials than from receiving standard
therapies.
Some professional organizations, like the National Comprehensive
Cancer Network (www.nccn.com), actively encourage the participation
of patients with cancer in clinical trials because they provide the best
management for any cancer patient.
What is informed consent?
Informed consent is a process through which people learn all about
the clinical trials they are interested in joining. During this process,
members of the clinical trial research team will explain:
n
n
n
The purpose of the study.
The factors used to decide if a patient is allowed to participate in the
study.
The tests, procedures, and visits participants will be expected to
agree to.
n
The type of treatment provided in the study.
n
The possible risks and benefits.
n
93
The rights of patients to decide whether or not to participate, and to
leave the study at any time.
Understanding Non-Hodgkin Lymphoma
The research team will answer your questions and provide written
information about the trial. If patients agree to participate in a clinical
trial, they will be asked to read and sign an informed consent form
that details all the trial information discussed and describes how their
records will be kept private.
Remember that even after signing the consent form, patients can
leave the study at any time.
Questions to Ask About a Clinical Trial
n
What is the purpose of this clinical trial?
n
Why are you recommending this clinical trial for me?
n
Who is sponsoring this trial (the National Cancer Institute, a
cancer center, a pharmaceutical/biotechnology company)?
Who has reviewed and approved this clinical trial?
n
Does this clinical trial include the use of a placebo (sugar pill)?
n
How long will the study last? Where will it take place?
n
What are the risks involved?
n
What are the possible benefits?
n
What are my responsibilities during the clinical trial?
Part 4
n
n
TIP
NT
PATIE
What kinds of tests, procedures, or treatments will be
performed? How many and how often?
n
Will I be in any discomfort or pain?
n
Will I be able to see my own doctor during the clinical trial?
n
What costs will I be responsible for?
n
What happens if my health gets worse during the clinical trial?
Clinical Trials and Advances in Treatment
94
What is the cost of participating in a clinical trial?
Clinical trials are very expensive undertakings for the study sponsor.
Patient costs vary depending on the study, who is sponsoring the
trial, what portion of the trial-related expenses the sponsor will cover,
and the patient’s health insurance coverage. Some health insurance
and managed healthcare providers will pay for the basic medical
procedures associated with the trial, such as lab tests, scans, and
hospitalization when required, while others may define clinical trials as
“experimental” or “investigational” and not cover some of the routine
costs, such as doctor visits, tests, or treatments. Medicare provides
coverage for patient care associated with government-sponsored
clinical trials.
If a patient is taking part in a National Cancer Institute (NCI) trial being
conducted at the National Institutes of Health (NIH) in Bethesda,
Maryland, the NCI will pay for the study drug and the costs related
to the study. A stipend for travel, food, and lodging is also provided.
Some cancer centers provide financial assistance or discounted rates
for room and board and have special research units that will pay for
study-related costs. Some organizations, including the Lymphoma
Research Foundation, provide financial assistance for treatmentrelated expenses.
Patients should ask their doctor what clinical trials may be most
appropriate for them. Here are some additional sources of clinical trial
information:
n
n
n
n
95
The Lymphoma Helpline at the Lymphoma Research Foundation at
(800) 500-9976.
Cancer centers in your area.
The Coalition of Cancer Cooperative Groups website at
www.cancertrialshelp.org.
The NIH websites www.cancer.gov and www.clinicaltrials.gov.
Understanding Non-Hodgkin Lymphoma
Part 4 — Clinical Trials
and Advances in Treatment
Chapter 10: Advances in Treatment of Patients With Non-Hodgkin
Lymphoma
Doctors and scientists around the world are working very hard to
improve currently available treatment options and find better and safer
drugs to treat patients with NHL. Advances are being made in different
areas including: genetics, treatments, and supportive care.
Drugs that are not yet approved for sale by the FDA are said to be
investigational. Some of these investigational drugs are being studied
in laboratory experiments using tissue culture cells and laboratory
animals. The drugs that are in more advanced stages of research are
being studied in patients in clinical trials.
Remember that today’s science is moving very fast. Please check
with the Lymphoma Research Foundation or the doctor for additional
information and recent updates.
For a detailed discussion of currently approved treatment options,
please see Chapter 6, “Treatments for Non-Hodgkin Lymphoma.”
Chemotherapy
Researchers are trying to develop new chemotherapy drugs, make
improved versions of existing drugs, and find better ways to combine
different doses and sequences of existing drugs. The goal is to make
drugs that are better at killing lymphoma cells while leaving healthy
cells alone (decreasing the chance of side effects).
Clinical Trials and Advances in Treatment
96
Part 4
The most common way for a patient to receive an investigational drug
is through a clinical trial. To find out more about getting access to
investigational drugs go to the website for the National Cancer Institute
at www.cancer.gov and search for “access to investigational drugs.”
Stem cell transplantation
Ongoing research in stem cell transplantation is focused on: finding
better ways to collect stem cells from the bone marrow or peripheral
blood; eliminating graft-versus-host disease in allogeneic (donor)
transplants; improving ways to remove all lymphoma cells from stem
cell samples used for autologous (self) transplants; and developing
more effective non-myeloablative (reduced-intensity) stem cell
transplants.
Monoclonal antibodies
Monoclonal antibodies are molecules made in the laboratory that
are designed to recognize and stick to specific molecules on cancer
cells. When a monoclonal antibody attaches itself to a cancer
cell, it can stop or slow down its growth or it can make it easier for
the immune system to recognize it and kill it. The success of the
monoclonal antibody rituximab (Rituxan) inspired researchers to
develop other monoclonal antibodies to treat patients with NHL. Many
monoclonal antibodies are being investigated in clinical trials, including
obinutuzumab (GA101), ocrelizumab, epratuzumab, lucatumumab
(HCD122), blinatumomab (AMG 103), AME-133v, and others.
Other targeted therapies
In addition to monoclonal antibodies that target molecules on cell
surfaces, many drugs are in development that target molecules inside
cancer cells. A better understanding of the biology and genetics of
NHL is helping researchers identify specific molecules in lymphoma
cells that may be good targets for new drugs. These specific
molecules usually have important roles in controlling the growth and
survival of lymphoma cells. The drugs that target these molecules are
broadly called targeted therapies. These drugs may kill the lymphoma
cells or slow down or stop their growth. Targeted therapies attack
cancer cells in a more specific way than chemotherapy drugs.
Many targeted therapies for NHL are being studied in laboratories and
in clinical trials. Examples include: immunomodulating agents (IMiDs)
such as lenalidomide (Revlimid), which target molecules involved
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Understanding Non-Hodgkin Lymphoma
in immune function; histone deacetylase (HDAC) inhibitors such as
romidepsin (Istodax) and vorinostat (Zolinza), which target molecules
that help control which proteins are produced by a cell; mammalian
target of rapamycin (mTOR) inhibitors such as temsirolimus (Torisel)
and everolimus (Afinitor), which target molecules in cell biochemistry
pathways involved in cell growth and division; inhibitors of Bcl2 such
as ABT-263 (navitoclax), which target molecules that prevent cell
death; aurora kinase inhibitors such as MLN8237 (alisertib), which
interfere with normal cell division; purine nucleoside phosphorylase
(PNP) inhibitors such as forodesine, which results in T- and B-cellspecific apoptosis (cell death); and inhibitors of B-cell receptor
molecules such as ibrutinib (PCI-32765) and GS-1101, which also
trigger cell death.
Proteasome inhibitors
Several novel proteasome inhibitors are also currently being tested
in clinical trials of various NHL types, including carfilzomib, NPI-0052,
CEP-18770, MLN9708, and others.
Vaccines
Researchers are trying to develop vaccines to help treat, not prevent,
lymphomas. The hope is that these vaccines would boost a person’s
own immune system so that it would recognize and kill lymphoma cells
early during the course of the disease. This type of vaccine therapy
is also being studied in other types of cancer such as prostate cancer
and melanoma.
There are no currently approved cancer vaccines for NHL, but several
are actively being tested in clinical trials.
Clinical Trials and Advances in Treatment
98
Part 4
Bortezomib (Velcade) is a proteasome inhibitor currently approved for
multiple myeloma and mantle cell lymphoma. Bortezomib is currently
being investigated, either alone or in combination with other drugs,
for other NHL types, including follicular lymphoma, diffuse large B-cell
lymphoma, marginal zone lymphoma, several T/NK-cell lymphomas,
and Waldenström macroglobulinemia.
ABOUT THE LYMPHOMA RESEARCH FOUNDATION
The Lymphoma Research Foundation (LRF) is the nation’s largest
non-profit organization devoted to funding innovative research and
providing people with lymphoma and healthcare professionals with
up-to-date information about this type of cancer. LRF’s mission is to
eradicate lymphoma and serve those touched by this disease.
The Foundation remains dedicated to finding a cure for lymphoma
through an aggressively-funded research program and by supporting
the development of improved therapies for people living with
lymphoma. LRF provides a comprehensive series of programs and
services for people with lymphoma, their loved ones, and caregivers.
How the Lymphoma Research Foundation Serves the
Lymphoma Community
Research
LRF remains dedicated to finding a cure for lymphoma through an
aggressively-funded research program. LRF supports innovative
research through Clinical Investigator Career Development Awards,
Fellowships, and several disease-specific research initiatives. These
focused initiatives include: Chronic Lymphocytic Leukemia/Small
Lymphocytic Lymphoma Initiative; Diffuse Large B-Cell Lymphoma
Initiative; Follicular Lymphoma Initiative; and Mantle Cell Lymphoma
Initiative and Consortium.
The Foundation’s volunteer Scientific Advisory Board (SAB),
comprised of 45 world-renowned lymphoma experts, guides the
Foundation’s research activities, seeking out the most innovative and
promising lymphoma research projects for support.
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Understanding Non-Hodgkin Lymphoma
Programs and Services
LRF provides a comprehensive series of programs and services for
the lymphoma community, including:
n
Clinical Trials Information Service
n
Disease-Specific Publications and Websites
n
In-person Workshops and Educational Forums
n
Lymphoma Helpline
n
Lymphoma Support Network
n
Online Resources, Teleconferences, and Webcasts/Podcasts
n
Patient Aid Grants
Professional Education
LRF is committed to educating healthcare professionals on the latest
developments in lymphoma diagnosis and treatment. The Foundation
offers a wide range of lymphoma-focused continuing education
activities for nurses, physicians, and social workers, including
workshops, conference symposia, and webcasts.
Public Policy and Advocacy
LRF represents the needs of people with lymphoma by supporting
public policies which seek to increase federal funding for lymphoma
research and ensure access to high quality cancer care. The LRF
Advocacy Program provides volunteer advocates with the resources
necessary to garner attention and support for those public policies
most important to the lymphoma community. There are currently more
than 5,000 LRF advocates in all 50 states and the District of Columbia.
About the Lymphoma Research Foundation 100
Chapter Network
Through its nationwide chapter network, LRF meets the needs of the
lymphoma community on the local level. Chapter volunteers reach out
to newly diagnosed patients; raise funds for research; and participate
in advocacy efforts. There are 18 chapters in 16 states.
Contact Information
LRF National Headquarters
115 Broadway, Suite 1301
New York, NY 10006
(212) 349-2910
Fax (212) 349-2886
[email protected]
www.lymphoma.org
LRF Helpline
(800) 500-9976
[email protected]
101 Understanding Non-Hodgkin Lymphoma