Similar to trials of rHuG-CSF and rHuEPO, investigators have assessed the clinical efficacy of combined rHuGM-CSF and rHuEPO treatment in patients with MDS. In small phase 2 trials of concurrent or sequential rHuEPO and rHuGM-CSF treatment, increases in Hb concentrations or decreased transfusion requirements occurred in 23-46% of patients (66-69). A 12-wk randomized, placebo-controlled trial of rHuGM-CSF (0.3-5.0 |g/kg/d) and rHuEPO therapy (150 U/kg three times weekly) stratified 66 MDS patients to endogenous EPO <500 or >500 U/L (70). Combined rHuGM-CSF and rHuEPO therapy significantly improved neutrophil counts, but platelet counts were unaffected. A trend toward reduced red blood cell transfusion requirements was observed in patients with EPO < 500 U/L, but only 9% of patients in the combined cytokine group achieved an Hb response (>2 g/dL). In a study of 19 patients, sequential rHuGM-CSF (3 |g/kg) and rHuEPO (60-120 U/kg) were administered weekly for 3 mo (71). Ten of 19 (53%) responded, with 7 patients achieving a good response and 3 patients a partial response. All responding RARS patients continued to have erythroid responses during 3-24 mo of follow-up, whereas one RA and two RAEB patients did not have continuing responses at 2-12 mo. Although these studies of rHuGM-CSF and rHuEPO treatment suggest some clinically important ery-throid responses, the combination of rHuG-CSF and rHuEPO is at least as effective and is generally better tolerated because of the greater toxicity associated with rHuGM-CSF.

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