A PILOT TRIAL OF 13-CIS-RETINOIC ACID AND ALPHA-TOCOPHEROL WITH RECOMBINANT-HUMAN-ERYTHROPOIETIN IN MYELODYSPLASTIC SYNDROME PATIENTS WITH PROGRESSIVE OR TRANSFUSION-DEPENDENT ANEMIAS

A pilot study was performed to determine the efficacy of 13-cis-retino ic acid (CRA) and alpha-tocopherol (AT) with increasing doses of recom binant human erythropoietin (rHuEPO) in anemic patients with primary m yelodysplastic syndrome (MDs), to determine response rate and to deter mine the dose requirement and long-term effects of rHuEPO therapy on t he transition to acute non-lymphocytic anemia and survival of these pa tients. Twenty-four consecutive MDS patients were entered into the stu dy. Patients were stratified according to their FAB classification at study entry. Therapy consisted of a 6 month trial of CRA (100 mg m(-2) day(-1)) and AT (800 mg day(-1)) with rHuEPO (150 units kg(-1) body w eight subcutaneously three times a week). The rHuEPO dose was escalate d to daily doses at 2 months, and 300 U kg(-1) body weight given three times a week for another 2 months and continuing therapy after 6 mont hs in responsive patients. Response was measured by elimination of tra nsfusions requirement (partial response, PR) and normal hemoglobin lev el and complete blood counts (complete response, CR). Observed respons es for the 23 evaluable patients were 2 CR and 6 PR (34.8%). Odds rati o analysis showed that patients with anemia alone were 14 times more l ikely to respond than patients with pancytopenia (p = 0.06). In our st udy, two patients (8%) transformed to acute leukemia in CRA + AT + rHu EPO-treated patients. Median survival of 34 months with a median follo w-up of 17 months (range 3-70 months) was observed. The response rates with the addition of rHuEPO to CRA and AT was similar but occurs earl ier at 2 months compared to 6-10 months with CRA and AT alone and did not alter survival. There was no increase in the risk for leukemia in the group treated with rHuEPO. Response to either therapy appeared to be limited to patients in the early stages of MDs. (C) 1998 Elsevier S cience Ltd. All rights reserved.