Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups

Preliminary independent reports of the Italian GIMEMA and the Spanish PETHE MA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and d isease-free survival rates. To better investigate these studies and the pro gnostic factors influencing re lapse risk, this study analyzed the updated results of 217 patients with PML/RAR alpha-positive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients receive d 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and id arubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of idarubicin and mitoxantrone with the omission o f nonintercalating agents. Depending on whether molecular relapses were cla ssified as censored or uncensored events, the 3-year Kaplan Meier estimates of relapse free survival (RFS) for the combined series were 90 +/- 2% and 86 +/- 2%, respectively. Minor differences observed between the 2 patient c ohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with i ndependent prognostic value. The resulting predictive model for RFS demonst rated its capability of segregating patients into low-risk (WBC count less than or equal to 10 x 10(9)/L, platelet count > 40 x 10(9)/L), intermediate -risk (WBC count less than or equal to 10 x 10(9)/L, platelets less than or equal to 40 x 10(9)/L), and high-risk (WBC count > 10 x 10(9)/L) groups, w ith distinctive RFS curves (P <.0001), The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduce d antileukemic efficacy and a simple predictive model may he used for risk- adapted therapy in this disease.(Blood. 2000;96:1247-1253) (C) 2000 by The American Society of Hematology.