Treatment of Acute Promyelocytic Leukemia: A Report of 70 Cases

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Abstract
Over a period of 14 years, we treated 70 cases of acute promyelocytic leukemia (APL) with 3 different chemotherapy protocols. In protocol 1, patients received high dose daunorubicin (DNR) alone for induction, followed by regular reinduction courses and continuous maintenance therapy with 6 mercaptopurine (6 MP) and methotrexate (MTX) during 3 years. In protocol 2, induction with high dose DNR and Ara C was also followed by regular reinduction courses, but without continuous maintenance therapy. Protocol 3 randomized high dose Amsacrine (AMSA) or Rubidazone in association with Ara C, for induction and consolidation, this was followed by reinduction courses and continuous maintenance therapy with 6 MP and MTX. During the induction all patients received, prophylactic heparinization and platelet transfusions. Fifty six patients (80%) achieved complete remission (CR), 13 patients (18.5%) had early death (ED) or hypoplastic death (HD), and 1 patient had true resistant leukemia. Only two patients died of hemorrhage. Median actuarial disease free survival (DFS) was 16.5 months and a plateau at 29.1% was reached after 29 months. Patients with fever at diagnosis had a significantly lower CR rate while age below 20 years and circulating blasts above 0.5 × 10(9)/1 were associated with shorter DFS. The CR rate did not significantly differ between protocols 1, 2 and 3 (87.5%, 80% and 60% respectively) but 9 of the 30 patients on protocols 2 or 3 had ED or HD, compared to 4 of the 40 treated with protocol 1 (p < 0.05). DFS was significantly shorter in protocol 2, which included no continuous maintenance chemotherapy, than in protocols 1 and 3. Median actuarial survival was significantly shorter in patients treated with protocols 2 or 3, compared to protocol 1. These results suggest that high dose DNR alone, associated with adequate prophylaxis of disseminated intravascular coagulation, gives very high CR rates in APL, with short periods of aplasia and limited toxicity. Combinations of an anthracycline or AMSA at the doses used with regular dose Ara C may be too toxic. Although this was not a randomized trial, our findings also suggest a possible benefit of prolonged continuous maintenance therapy with 6 MP and MTX in APL.