Sustained response to recombinant human erythropoietin and intermittent all-trans retinoic acid in patients with myelodysplastic syndromes.

In vitro studies suggest that all-trans retinoic acid (ATRA) synergizes with erythropoietin (EPO) for the stimulation of hematopoiesis in patients with myelodysplastic syndrome (MDS). A clinical trial was performed to evaluate whether a combination of these agents was effective in relieving the cytopenias associated with MDS. Twenty-seven patients with low- or intermediate-risk MDS were enrolled in a 12-week study. ATRA was administered orally at the dose of 80 mg/m(2) per day in 2 divided doses for 7 consecutive days every other week. Recombinant human EPO was given subcutaneously 3 times a week. The EPO dose was initiated at 150 U/kg and was increased to 300 U/kg if after 6 weeks there was no or there was suboptimal erythroid response. Patients who responded to therapy were continued on ATRA and EPO at the same doses for 6 additional months (extension phase). Further treatment was given to patients with a continued response. Clinically significant erythroid responses with increases of hemoglobin levels of at least 1 g/dL or reduction of transfusion needs were seen in 13 (48%) patients, with 4 showing improved responses after dose escalation of EPO. Ten (37%) patients displayed continued responses during 6 months of extended treatment, and 7 (26%) are still responsive after a follow-up period of 13 months. Neutrophil responses were observed in 5 of 12 patients with neutropenia, and platelet responses were observed in 6 of 9 patients with thrombocytopenia. Three patients displayed trilineage responses that were sustained during continuation therapy. Side effects were observed in all patients but were of mild entity and did not require discontinuation of therapy. It is concluded that the combination ATRA + EPO is an effective and well-tolerated treatment for patients with low- and intermediate-risk MDS. The optimal ATRA and EPO schedule and the role of maintenance treatment remain to be determined and warrant further investigation.