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Management of Anemia in Patients With Hematologic Malignancies

Management of Anemia in Patients With Hematologic Malignancies

ABSTRACT: Anemia is common in patients with hematologic malignancies, and it has negative effects on their quality of life. The current clinical practice guidelines recommend erythropoietic therapy in patients with cancer- or chemotherapy-related anemia, but anemia is often undertreated in patients with hematologic malignancies. Several randomized controlled trials have shown that treatment with erythropoiesis-stimulating proteins such as epoetin alfa (Procrit), epoetin beta, and darbepoetin alfa (Aranesp) increases hemoglobin levels, reduces the need for red blood cell transfusions, and improves quality of life in patients with hematologic malignancies and anemia receiving chemotherapy. Furthermore, preliminary data from a recent open-label study suggest that early treatment of mild anemia in patients with hematologic malignancies treated with chemotherapy produces marked improvements in quality of life and productivity. Increasing patients' hemoglobin levels may also improve their cognitive function. These findings support the use of erythropoietic therapy to manage anemia in patients with hematologic malignancies who are treated with chemotherapy.

Anemia is a common complication in patients with hematologic malignancies. A number of factors contribute to low hemoglobin (Hgb) levels in these patients, including insufficient erythropoiesis caused by tumor infiltration of the bone marrow or chemotherapy-induced myelosuppression, anemia of chronic disease caused by decreased production of serum erythropoietin, nutritional deficiency, hemolysis, and bleeding.[1] The prevalence of anemia in patients with hematologic malignancies varies by cancer type and stage, with approximately one-quarter to one-half of patients having anemia at the time of diagnosis.[2-5] In the European Cancer Anaemia Survey, anemia (Hgb < 12 g/dL) was seen at least once in the 6-month survey period in 73% of the subjects with lymphoma or myeloma and in 68% of those with leukemia.[6] The consequences of anemia in patients with cancer include fatigue, weakness, impaired concentration, and diminished quality of life (QOL).[7-9] Furthermore, low Hgb levels may have a negative effect on prognosis and survival.[10]

Current clinical practice guidelines recommend erythropoietic therapy in patients with cancer- or chemotherapy-related anemia. The clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology recommend that erythropoietic therapy be initiated in patients with chemotherapy-induced anemia and Hgb levels of 10 g/dL or less.[11] These guidelines suggest that erythropoietic therapy should be initiated in patients with hematologic malignancies only if an increase in Hgb levels has not been achieved through cytoreduction with chemotherapy. The clinical practice guidelines of the National Comprehensive Cancer Network recommend that erythropoietic therapy be considered in symptomatic patients with cancer- or chemotherapy-related anemia and Hgb levels of less than 11 g/dL.[12]

Treatment with the erythropoiesis-stimulating protein epoetin alfa (Procrit, recombinant human erythropoietin) significantly increases Hgb levels, decreases the need for red blood cell transfusions, and improves QOL in patients with chemotherapy-related anemia.[13-17] Similarly, treatment with darbepoetin alfa (Aranesp), a novel erythropoiesis-stimulating protein with a longer half-life than that of epoetin alfa, has been shown to improve hematologic measures, fatigue, QOL, and productivity in patients with chemotherapy-induced anemia.[18-24] However, despite the known benefits of treating anemia in patients with cancer, it is often undertreated in those with hematologic malignancies.[6]

Management of Anemia in Hematologic Malignancies

Several clinical trials of erythropoietic therapy in patients with hematologic malignancies have been conducted in the past few years. Epoetin alfa was shown to correct anemia and improve QOL in a randomized placebo-controlled double-blind trial in anemic patients with solid or nonmyeloid hematologic malignancies treated with nonplatinum chemotherapy.[25, 26] Patients were given epoetin alfa (150-300 IU/kg) or placebo by subcutaneous (SC) injection three times a week for up to 28 weeks. In a subset analysis of data from patients with hematologic malignancies (46% of patients), the mean pretreatment Hgb level was 9.9 g/dL in the epoetin alfa group and 9.7 g/dL in the placebo group.[25]

Outcomes in the patients with hematologic malignancies are shown in Table 1. Fewer patients with hematologic malignancies treated with epoetin alfa required red blood cell transfusions after week 4 than those treated with placebo (25% vs 43%), and the mean increase in Hgb levels was also markedly greater in patients treated with epoetin alfa (2.2 vs 0.3 g/dL), with differences between the groups evident after 2 weeks of treatment. Furthermore, more patients with hematologic malignancies treated with epoetin alfa had a response (defined as an increase in Hgb level of 2 g/dL or more that was unrelated to transfusions) than those treated with placebo (75% vs 17%). These efficacy results paralleled those in the overall study population; however, statistical analyses of efficacy measures were not performed by tumor subgroup because the trial lacked the power to discriminate treatment differences by subgroup.

Quality of life was also evaluated in this trial by using the Functional Assessment of Cancer Therapy-General (FACT-G) and the FACT-Anemia (FACT-An, including the FACT- Fatigue [FACT-F] subscale), as well as the Linear Analog Scale Assessment. There was an improvement on all QOL scales and subscales in patients with hematologic malignancies treated with epoetin alfa; in contrast, QOL decreased in the patients treated with placebo, despite their Hgb levels being maintained with transfusions.[25]

Epoetin beta was shown to reduce transfusion requirements and improve QOL in a randomized double-blind placebo-controlled trial in patients with low-grade non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or multiple myeloma (MM) and severe anemia.[27] Patients had Hgb levels of 10 g/dL or less with a transfusion requirement of two or more units of packed red blood cells in the 3 months before study entry and inadequately low endogenous serum erythropoietin levels. Patients were randomized to epoetin beta 150-300 IU/kg (n = 170) or placebo (n = 173) by SC injection three times a week for 16 weeks. The mean pretreatment Hgb levels were 9.2 g/dL in the epoetin beta group and 9.3 g/dL in the placebo group.

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