Management of Anemia in Cancer Patients

Aknar Calabrich; Artur Katz

Future Oncol. 2011;7(4):507-517.

Blood Transfusions

The use of blood transfusions to correct anemia is a therapeutic modality for which there is less literature available for patients with cancer. Consequently, few studies are able to provide high-level evidence on the efficacy and safety of this modality. The chief aim of transfusion is to immediately correct the signs or symptoms resulting from anemia.^[65] Typically, there is a growing need for blood transfusions in individual cancer patients as the number of chemotherapy cycles administered increases. However, there is wide variation in the level of hemoglobin that triggers blood transfusions among the various studies and among different types of cancers.^[66]

There is general medical consensus that blood transfusion should be used in patients with terminal illness when there is acute blood loss or chronic deterioration of the patient, when hemoglobin levels are below 7 g/dl, in anemic patients with respiratory or heart symptoms or in patients with anemia due to chemotherapy.^[67] However, the trigger level of hemoglobin and its target values have not been determined. On the other hand, the EORTC guidelines mention that patients with hemoglobin levels of less than 9 g/dl should primarily be evaluated for the need of transfusions.^[43] The ASH/ASCO guidelines suggest that blood transfusions may be an option for the correction of anemia associated with chemotherapy when hemoglobin levels are less than 10 g/dl or for elderly patients with limited cardiopulmonary reserve, patients with coronary disease or symptomatic angina, those with substantial reduction in exercise capacity or those with difficulty in performing daily activities.^[45]

The results of a number of studies evaluating the impact of transfusion on mortality in critically ill patients are conflicting. One study of 56 esophageal cancer patients receiving chemoradiation therapy demonstrated that blood transfusions increased overall survival.^[68] However, there is evidence in the literature that blood transfusion may have a negative impact on the progression of disease.^[69] Fyles and colleagues analyzed the published data from a randomized trial and found that transfusion in anemic patients with cervical cancer did not result in benefit.^[70] In a retrospective study of 70,542 patients hospitalized with cancer, the use of blood transfusion was associated with higher rates of venous and arterial TEs, in addition to an increased risk of hospital mortality.^[71] However, the causal relationship could not be established owing to the retrospective nature of the study. There are other potential hazards related to blood transfusion. Some of the currently known blood contaminants include hepatitis A virus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 8, Toxoplasma gondii, parvovirus B-19, West Nile virus, spongiform encephalopathy prions, Trypanosoma cruzi, Babesia species and Plasmodium species, although the introduction of numerous safety interventions for infectious organisms has dramatically decreased the incidence of transfusion-related infections.^[72,73] Other transfusion reactions include febrile nonhemolytic transfusion reaction, bacterial infection, acute hemolytic reaction, anaphylactic reaction, transfusion-associated acute lung injury, volume overload, iron overload, delayed hemolytic reaction, transfusion-associated graft-versus-host disease and post-transfusional purpura.^[1] At present, blood transfusion is not a proven safe alternative to ESAs, as comparative studies have not been performed and, in contrast to ESAs, little is known about the potential long-term side effects.

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Table 1. Grading of anemia according to the National Cancer Institute.
Grade	Hemoglobin level/definition
0	≥lower limit of normal
1	10 g/dl to lower limit of normal
2	8.0–9.9 g/dl
3	6.5–7.9 g/dl
4	<6.5 g/dl
5	Death

Data taken from [101].

Table 2. Recommendations for the use of erythropoiesis-stimulating agents in patients with nonhematological malignancies.
Organization	Anemia related to chemotherapy	Untreated patients	Patients treated with curative intent	Ref.
ASH/ASCO	ESAs indicated for Hb ≤10 g/dl. Hb target is lowest value to avoid BT. BT is an option If Hb is between 10 and 12 g/dl, consider ESAs according to clinical condition. BT is an option	ESAs are not recommended	There is no specific recommendation	[45]
NCCN	BT if immediate correction is necessary Consider treatment with ESAs by US FDA indications/dosing/dosing adjustments, under REMS	BT according to symptoms ESAs are not recommended	ESAs are not recommended	[103]
US FDA	Therapy should not be initiated at Hb levels ≥10 g/dl Use the lowest dose of ESAs able to raise the levels of Hb values to avoid BT	ESAs are not recommended	ESAs are not recommended	[104]
EORTC	ESAs should be initiated at an Hb level of 9–11 g/dl based on anemia-related symptoms ESAs may be considered in selected asymptomatic patients with a Hb level of 11–11.9 g/dl if this would prevent a further decline in Hb iv. iron use should be reserved for patients with absolute or functional iron deficiency	ESAs may be given in selected patients with a Hb level of 9–11 g/dl	There is no specific recommendation	[43]

ASCO: American Society of Clinical Oncology; ASH: American Society of Hematology; BT: Blood transfusion, EORTC: European Organisation for Research and Treatment of Cancer; ESA: Erythropoiesis-stimulating agent; Hb: Hemoglobin; iv.: Intravenous; NCCN: National Comprehensive Cancer Network; REMS: Risk evaluation and mitigation strategy.

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Executive Summary

Erythropoiesis-stimulating agents

Erythropoiesis-stimulating agents (ESAs) are capable of increasing hemoglobin levels in most anemic patients with cancer.
Using ESAs to treat anemia in cancer patients reduces transfusion requirements and improves quality of life, predominantly by reducing fatigue.
ESAs increase the risk of thromboembolic events.
During chemotherapy, ESA treatment should be initiated when hemoglobin values are lower than 10 g/dl.
There is no evidence of increased mortality when the target hemoglobin levels during treatment with ESAs were less than 12 g/dl in patients receiving anticancer treatment.
ESAs should not be used in patients with cancer who are not receiving chemotherapy.

Iron

Chemotherapy is associated with abnormal iron metabolism.
Another mechanism contributing to iron deficiency in cancer patients is the low bioavailability of orally administered iron.
The use of intravenous iron (and not oral iron) during treatment with ESAs may improve hemoglobin levels even in the absence of depleted iron stores (or absolute iron deficiency).
Recommendations for the optimal formulations, doses and treatment schemes of iron supplementation concurrently with ESA treatment in cancer-related anemia need to be established.

Blood transfusion

Blood transfusion is capable of immediately correcting the signs or symptoms resulting from anemia.
There is wide variation in the levels of hemoglobin that are used to justify blood transfusions among the various studies and among different types of cancers.
There are several acute hazards related to blood transfusion, and long-term side effects have not been properly studied.

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Management of Anemia in Cancer Patients

Blood Transfusions

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