A modified AIDA protocol with anthracycline-based consolidation results inhigh antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia

The Spanish PETHEMA group designed a protocol for newly diagnosed PML/RAR a lpha-positive acute promyelocytic leukemia (APL) in which induction and con solidation followed the original AIDA regimen, except for the omission of c ytarabine and etoposide from consolidation. Induction consisted of 45 mg/m( 2) all-trans retinoic acid (ATRA) daily until complete remission (CR) and 1 2 mg/m(2) idarubicin on days 2, 4, 6, and 8. Patients in CR received 3 mont hly chemotherapy courses: idarubicin 5 mg/m(2)/d x 4 (course no. 1), mitoxa ntrone 10 mg/m2/d x 5 (course no. 2), and idarubicin 12 mg/m2/d x 1 (course no. 3). Maintenance therapy consisted of 90 mg/ m(2)/d mercaptopurine oral ly, 15 mg/m(2)/wk methotrexate intramuscularly, and, intermittently, 45 mg/ m(2)/d ATRA for 15 days every 3 months. Between November 1996 and December 1998, 123 patients with newly diagnosed PML/ RAR alpha-positive APL from 39 centers were enrolled. A total of 109 patients achieved CR (89%; 95% confi dence interval [CI], 83 to 95), 12 died of early complications, and the rem aining 2 were resistant. Consolidation treatment was associated with very l ow toxicity and no deaths in remission were recorded. Molecular assessment of response by reverse transcriptase-polymerase chain reaction (RT-PCR) sho wed conversion to PCR-negative in 48 of 99 (51%) and 82 of 88 patients (93% ) after induction and consolidation, respectively. The 2-year Kaplan-Meier estimates of overall survival and event-free survival were 82% +/- 4% and 7 9% +/- 4%, respectively. For patients who achieved CR, the 2-year disease-f ree survival (DFS) was 92% +/- 3%. These data indicate that a significant r eduction in toxicity might be obtained in APL using a less intensive consol idation without apparently compromising the antileukemic effect. These resu lts also suggest a minor role for cytarabine and etoposide in the treatment of newly diagnosed PML/RAR alpha-positive APL patients. (C) 1999 by The Am erican Society of Hematology.