Download 7- Anaemia

Anaemia in Cancer Patients
Prof. Dr. Khaled Abouelkhair, PhD
Medical Oncology SCE, Royal College, UK
Ass. Professor of Clinical Oncology
Mansoura University, Egypt
Outlines

Anaemia






Definition
Causes
Laboratory diagnosis
Manifestations
Clinical importance
Treatment and ESAs
Anaemia



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.
The physiologic regulation of red cell
production by tissue oxygen tension.
Causes of Anaemia in Cancer






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.
Increased destruction
Anaemia is a major contributing factor to cancer related
fatigue beside many others e.g. psychological,
nutritional and disability caused by cancer.
NCI Classification of Anaemia





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





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?




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.
Evaluation…Not every anaemia in Cancer
patients is related to chemotherapy




The evaluation of the patient with anaemia requires a careful
history and physical examination.
Nutritional history related to drugs or alcohol intake and
family history of anaemia should always be assessed.
Certain geographic backgrounds and ethnic origins are
associated with an increased likelihood of an inherited
disorder of the haemoglobin molecule or intermediary
metabolism.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency and
certain haemoglobinopathies are seen more commonly in
those of Middle Eastern or African origin.
Laboratory studies
Pay attention to….







Anisocytosis
Poikilocytosis
Polychromasia
Reticulocytic count
Sickle cells
Howell-jolly bodies
Reticulocytes Index
Blood Smear
Normal blood smear
(Wright stain).
Howell-Jolly bodies.
Iron Deffiency
Myelofibrosis
Macrocytosis
Target Cells
Red Cell Fragmentation
Reticulocytosis
Burr Cell ….Uraemia
Spur Cells..Acanthocytes
Iron Studies





The serum iron ranges from 9 to 27 μmol/L (50–150 μg/dL).
While the normal TIBC is 54–64 μmol/L (300–360 μg/dL);
the normal transferrin saturation ranges from 25 to 50%.
A diurnal variation in the serum iron leads to a variation in
the percent transferrin saturation.
The serum ferritin is used to evaluate total body iron
stores. Adult males have serum ferritin levels that average
∼100 μg/L, corresponding to iron stores of ∼1 g. Adult
females have lower serum ferritin levels averaging 30 μg/L,
reflecting lower iron stores (∼300 mg).
A serum ferritin level of 10–15 μg/L represents depletion of
body iron stores
Reticulocytic Index
The physiologic classification of anaemia.
Treatment of Chemotherapy induced Anaemia



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



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




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




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


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.
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:






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
ESAs




However…further researches proved a decrease in
overall survival and association with tumor progression,
thromboembolic events, hypertension and even death.
Failed to show improvement of patient’s well being,
enhance quality of life or alleviate fatigue.
Not indicated for cancer patients not on
myleosuppressive chemotherapy…RT, Hormone or
biologic.
Not used as a substitute for urgent PRBCs transfusion
to rapidly correct anaemia.
Epoetin Alfa (Eprex)








Prefilled Syringe
Dose 150U/Kg IV/SC 3 times weekly or
40,000 U SC once weekly until completion of
chemotherapy course.
Needs Iron supplement and weekly monitor of Hb levels.
Target of treatment is increase of Hb level by 1 Gm/4
weeks treatment.
Stop if Hb reaches 10 Gm and the patient is asymptomatic.
If target level not reached after 4 weeks; increase to
60,000 U once weekly and keep monitoring.
if Hb increased by more than 1Gm in any 2-weeks period
reduce by 25%.
Eprex….Side Effects






Hypertension is common…15-25%
VTE is serious……8%
Fever…..25%
Pruritus rash and headache about 15% each
Increased risk of serious cardiovascular
events.
Rare but fatal…red cell aplasia, Seizures,
severe allergic reactions.
Recent Guidelines:

Restricted ESAs use to only one indication chemotherapy
induced anaemia with restrict precautions:






Lower target Hb levels to 10-12 Gm/dl.
Meticulous and continuous follow up of Hb levels.
Only if the patient’s treatment of palliative intent.
Anaemia in cancer but not myeloid cancers.
DVT prophylaxis is advised especially in high risk
patients.
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.
What is your Role?






Read your patient’s CBC and symptoms carefully.
Define the type of anaemia: Size, normo or
hypochromic.
If microcytic hypochromic ask for Iron studies i.e Iron,
TIBC, Ferritin.
Give Iron…relation to food…tea and Coffee.
Give Folic and Vit B12.
If chemotherapy for cure…Do not hold chemotherapy
if Hb 8-10 and the patient is asymptomatic…proceed
with chemotherapy and start Iron supplement +/transfusions.
Case Study

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.