Very low doses of GM-CSF administered alone or with erythropoietin in a plastic anemia

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purpose and rationale: There has been no previously published experience with granulocyte-macrophage colony-stimulating factor (GM-CSF) at doses less than 15 μg/m 2/d in patients with aplastic anemia, and most observations have been made at doses of 100 to 500 μg/m 2/d (2.5 to 12.5 μg/kg/d). The benefits of using considerably lower doses, if effective, should include a decrease in cost and in side effects. We have therefore used very low doses of GM-CSF to treat a group of patients with aplastic anemia. Additionally, since severe anemia is often a problem in these patients, we recently started administering erythropoietin along with the GM-CSF. Herein we report the results of verylow-dose GM-CSF therapy in patients with aplastic anemia and our preliminary findings in those individuals who received combination therapy. patients and methods: We administered recombinant human GM-CSF subcutaneously at doses of 5 to 20 μg/m 2/d “very-low-dose GMCSF”) to 12 patients with aplastic anemia. In addition, a 13th patient received erythropoietin together with the GM-CSF regimen, and three of the 12 individuals who initially received 1 or more months of GM-CSF alone were later also given erythropoietin (4,000 U/d subcutaneously). results: In five of 12 patients (42%) treated with very-low-dose GM-CSF, an increase in neutrophil counts (2.0- to 6.7-fold) was noted, and one of these subjects attained a bilineage response (neutrophil counts, 0.3 to 1.75 × 10 9/L; platelet counts, 8 to 169 × 10 9/L). Moreover, a sixth patient showed a rise in platelet counts (19 to 80 × 10 9/L) without a concomitant increase in neutrophils. Constitutional side effects were minimal. Combining erythropoietin and verylow-dose GM-CSF produced a bilineage response (neutrophils, 1.0 to 3.0 × 10 9/L; hemoglobin, 7.4 to 9.4 g/dL) in the one patient who received erythropoietin together with the GMCSF from the time that GM-CSF was initiated. In one of the other patients who were given combination therapy, the addition of erythropoietin appeared to enhance the response; this patient demonstrated a neutrophil response to GM-CSF alone and a trilineage response (neutrophils, 0.8 to 3.75 × 10 9/L; hemoglobin, 7.0 to 13.1 g/dL; and platelets, 10 to 34 × 10 9/L) to the combination. No toxicity was associated with the addition of erythropoietin. conclusions: Our observations suggest that (1) very low doses of GM-CSF (5 to 20 μg/m 2/d subcutaneously) may be used initially in neutropenic patients with aplastic anemia, and the dose subsequently increased only in patients who do not respond; and (2) the administration of erythropoietin together with GM-CSF is well tolerated, can augment responsiveness in some patients, and deserves further study.