Download 3- Anemia And Thrombocytopenia

Anaemia/ Thrombocytopenia in
Cancer Patients
Prof. Dr. Khaled Abulkhair, PhD
Medical Oncology SCE, Royal College, UK
Ass. Professor of Clinical Oncology
Mansoura University, Egypt
Outlines
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Anaemia/Fatigue
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Definition
Causes
Manifestations
Clinical importance
Treatment and ESAs
Thrombocytopenia
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Definition
Clinical importance
Treatment
Anaemia
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Anaemia is “The condition of having less than the
normal number of red blood cells or less than the
normal quantity of hemoglobin in the blood. The
oxygen-carrying capacity of the blood is, therefore,
decreased.”
Anaemia can result from the tumor itself (Anaemia of
cancer) as well as from cancer treatments, especially
myleosuppressive chemotherapy (chemotherapyinduced Anaemia).
According to The European Cancer Anaemia survey
(ECAS), Anaemia affects 67% of cancer patients.
Causes of Anaemia
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Uncontrolled pain can cause Anaemia and through
many factors one of them is decreased appetite.
Decreased RBC production by treatment of cancer e.g.
chemotherapy and or radiotherapy.
Decreased or inappropriate endogenous erythropoietin.
Decreased body stores of important factors e.g. Vit.
B12, Folic acid and Iron.
Anaemia is a major contributing factor to cancer related
fatigue beside many others e.g. psychological,
nutritional and disability caused by cancer.
The physiologic regulation of red cell
production by tissue oxygen tension.
NCI Classification of Anaemia
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Grade 0: within normal limits, Hb values are
12.0 to 16.0 g/dL for women and 14.0 to
18.0 g/dL for men.
Grade 1: mild (Hb 10 g/dL to normal limits)
Grade 2: moderate (Hb 8.0 to 10.0 g/dL)
Grade 3: serious/severe (Hb 6.5 to 7.9 g/dL)
Grade 4: life threatening (Hb less than 6.5
g/dL).
Manifestations of Anaemia
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Manifestation and severity of anaemia vary considerably among
individual patients.
Mild-to-moderate anaemia can cause typical symptoms including
headache, palpitations, tachycardia and shortness of breath.
Chronic anaemia may result in severe organ damage affecting the
cardiovascular system, immune system, lungs, kidneys, muscles and the
central nervous system.
In addition to physical symptoms, the subjective impact of cancerrelated anaemia on quality of life (QoL),mental health and social
activities may be substantial.
Clinical studies have reported correlations between Hb levels and
quality of life domains, for example mood, appetite (Leitgeb 1994),
fatigue and the ability to work (Cella 1998; Thomas 1998).
Clinical Importance?
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Its effect on the tumour itself. For malignant diseases such
as Hodgkin’s Disease (HD), chronic lymphocytic leukaemia
(CLL), cervical carcinoma and cancer of the head and neck,
anaemia has been reported to be an independent prognostic
factor.
Anaemia, with the consequence of increased tumour hypoxia,
results in a poorer response to radio- or chemotherapy.
Severe symptoms of anaemia may also necessitate dose
reduction or delay of chemotherapy.
All these factors may lead to a higher tumour burden and a
decreased overall survival.
Treatment of Anaemia
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For long time blood transfusions was the only way to
improve anaemia, followed in early nineties by the use of
Erythropoiesis stimulating agents (ESAs).
The literature reports a critical degree of anaemia as a Hb
level below 8 g/dL, while mild to moderate anaemia (Hb
level 8-10 g/dL) usually has been left untreated (Carson
2012; Cella 1999).
Although homologous blood transfusion is the fastest
method to alleviate symptoms, short- and long-term risks
exist.
Transfusions….. Gold Standard
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Potential complications associated with blood transfusion
are transmission of infectious diseases, transfusion
reactions, allo-immunisation, over-transfusion and immune
modulation
This method remains the best way of rapidly ameliorating
anaemic symptoms and target to maintain Hb between 8 –
10 and decrease anaemia related symptoms
However, the effect of the treatment is short-lived and
there are several risks involved even with the widespread
testing of donors. This is why ESAs were introduced to
clinical practice.
ESAs…. A hope turned into a hill
What we expect to be this
Turned in reality to be that
ESAs
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Recombinant human erythropoietin is a treatment option
for cancer- related anaemia. Human erythropoietin is an
acidic glycoprotein hormone.
Approximately 90% of the hormone is synthesised in the
kidney and 10% in the liver (Koury 1988; Koury 1991).
Basal production maintains a relatively constant plasma
concentration of erythropoietin in individuals, within a
range from 9 to 26 mU/mL.
Tissue hypoxia is the most important trigger for increased
synthesis.
ESAs
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The effects of erythropoietin in the bone marrow are
mediated by a specific surface receptor located mainly on
erythroid progenitor and precursor cells (D´ Andrea 1989;
Spivak 1994b).
Two major functions of erythropoietin are described:
stimulating progenitor cell proliferation and maintaining their
viability.
In 1985, Lin et al isolated EPO and coded its gene sequence
Several short- and long-lasting forms of recombinant human
erythropoiesis-stimulating agents (ESAs) are available:
Types of ESAs
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Epoetin-a and Epoetin-ß and darbepoetin-a (Darbepo)
(Glaspy 2003; Halstenson 1991;Hedenus 2002; Joy 2002;
Storring 1998; Vansteenkiste 2002). Recently:
 Novel ESA molecules, such as continuous erythropoietin
receptor activator (CERA) (Gascon 2008)
 Biosimilars (epoetin theta, epoetin delta) have been
developed (Jelkmann 2010).
Clinical trials directly comparing Epo and Darbepo
have been published and suggest that Epo and
Darbepo are similarly effective with regard to Hb
response and proportion of patients transfused.
Doses and considerations
Impact of ESAs
In the early 1990s ESAs were shown to alleviate Anaemia
in cancer patients receiving chemotherapy. Hence ESAs
were used extensively in clinical practice and high Hb
levels up to 16 Gm/dl were targeted.
Earlier Studies ESAs were found to:
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Increase Haemoglobin (Hb) levels
Reduce the need for red blood cell transfusions
Improve quality of life (QoL) through alleviation of anaemic
symptoms e.g. fatigue
Increase overall survival
However…further researches suggest a decrease in overall
survival and association with tumor progression,
thromboembolic events, hypertension and even death.
Recent Guidelines:
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Restricted ESAs use to only one indication chemotherapy
induced anaemia with restrict precautions:
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Lower target Hb levels to 12 Gm/dl.
Meticulous and continuous follow up of Hb levels.
Only if the patient’s treatment of palliative intent.
FDA currently requires these agents to be prescribed
only under REMS (risk evaluation and mitigation strategy
for ESAs). With full explanation to the patients about the
side effects and risk of tumour progression.
REMS: Risk Evaluation and
Mitigation Strategy for ESAs
Requirements of the REMS program:
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All patients who are prescribed and receive ESAs must be
provided with a medication guide on therapy initiation and with
each dose, explaining the risks and benefits of these agents.
Patients will also be asked to sign an acknowledgment form that
confirms they have talked with their health care professional
about the risks of ESAs (may cause tumors to grow faster, may
cause patients to die sooner, and may cause patients to develop
blood clots or heart problems).
Health care providers prescribing ESAs to patients with cancer
must be enrolled in the ESA APPRISE (Assisting Providers and
cancer Patients with Risk information for the Safe use of ESAs).
Thrombocytopenia
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Platelets are a major factor in maintenance of
blood clotting process.
Decreased platelets count below 100,000/mm3.
What is the normal platelet Count?
Risk of bleeding is not increased till the count
drops below 10,000/mm3.
Again the Gold Standard is platelet transfusion
with nearly the same side effects as blood
transfusion.
Oprelvekin
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Platelet transfusion is recommended if count drops
below 10,000 or above 10,000 while the patient
symptomatic with bleeding or will be subjected to
major surgeries.
Recently Oprelvekin (Interleukin – 11) as a solution
for chemotherapy induced thrombocytopenia in non
myeloid cancers.
Oprelvekin is given as single daily dose by S.C
route to start 6-24 Hours post chemotherapy and
continued till count is higher than 50,000.
Oprelvekin
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It should not be given more than 21 days.
It should be stopped at least 2 days before
next cycle.
Expensive drug with common adverse effects
making it not cost effective.
Dose 50 microG/Kg SC / day. Start at least 24
H after chemotherapy.
Case Study
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A 38 y.o female recently diagnosed with early stage
breast cancer presented for her 3rd cycle of
chemotherapy, however, she is complaining of fatigue
and her Hb level is 8 Gm/dl decreasing from 11 Gm/dl
at diagnosis. What you will do?
A.
B.
C.
D.
Give her Iron supplement and delay her treatment for one
week.
Start ESAs plus iron and give her cycle.
Start ESAs with Iron and delay her cycle till Hb is at least 10
Gm/dl.
Transfuse with PRBCs and give her cycle once Hb is 10
Gm/dl.
Case II
Large cell lymphoma is considered intermediate
(between indolent and highly aggressive) in tumor
growth and biology. Large cell lymphoma is sensitive
to chemotherapy and potentially curable. Metastatic
colorectal cancer is considered slow growing. Although
responses to chemotherapy commonly occur and
chemotherapy can prolong survival (by months),
metastatic colorectal cancer is not generally
considered curable with chemotherapy. Given these
differences between large cell lymphoma and
metastatic colorectal cancer, which statement is most
accurate?
A. Patients with large cell lymphoma should receive allopurinol
before the first cycle of chemotherapy because they are at an
increased risk of developing TLS.
B. Patients with metastatic colorectal cancer should receive
allopurinol before the first cycle of chemotherapy because they are
at an increased risk of developing TLS.
C. Patients with large cell lymphoma should receive pamidronate
before the first cycle of chemotherapy because they are at an
increased risk of developing hypercalcemia.
D. Patients with metastatic colorectal cancer should receive
pamidronate before the first cycle of chemotherapy because they
are at an increased risk of developing hypercalcemia.
Case III
An 18-year-old man is about to begin chemotherapy
for acute lymphoblastic leukaemia. On today’s
complete blood cell count (CBC), his haemoglobin is
7 g/dL, and he is experiencing fatigue. Which is the
best treatment recommendation?
A. Initiate epoetin.
B. Transfuse with packed red blood cells (RBCs).
C. Delay chemotherapy treatment until haemoglobin recovers.
D. Reduce chemotherapy doses to prevent further decreases in
haemoglobin.
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