A Modified AIDA Protocol With Anthracycline-Based Consolidation Results in High Antileukemic Efficacy and Reduced Toxicity in Newly Diagnosed PML/RAR?-Positive Acute Promyelocytic Leukemia

The Spanish PETHEMA group designed a protocol for newly diagnosed PML/RAR?-positive acute promyelocytic leukemia (APL) in which induction and consolidation followed the original AIDA regimen, except for the omission of cytarabine and etoposide from consolidation. Induction consisted of 45 mg/m2 all-trans retinoic acid (ATRA) daily until complete remission (CR) and 12 mg/m2 idarubicin on days 2, 4, 6, and 8. Patients in CR received 3 monthly chemotherapy courses: idarubicin 5 mg/m2/d × 4 (course no. 1), mitoxantrone 10 mg/m2/d × 5 (course no. 2), and idarubicin 12 mg/m2/d × 1 (course no. 3). Maintenance therapy consisted of 90 mg/m2/d mercaptopurine orally, 15 mg/m2/wk methotrexate intramuscularly, and, intermittently, 45 mg/m2/d ATRA for 15 days every 3 months. Between November 1996 and December 1998, 123 patients with newly diagnosed PML/RAR?-positive APL from 39 centers were enrolled. A total of 109 patients achieved CR (89%; 95% confidence interval [CI], 83 to 95), 12 died of early complications, and the remaining 2 were resistant. Consolidation treatment was associated with very low toxicity and no deaths in remission were recorded. Molecular assessment of response by reverse transcriptase-polymerase chain reaction (RT-PCR) showed 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 79% ± 4%, respectively. For patients who achieved CR, the 2-year disease-free survival (DFS) was 92% ± 3%. These data indicate that a significant reduction in toxicity might be obtained in APL using a less intensive consolidation without apparently compromising the antileukemic effect. These results also suggest a minor role for cytarabine and etoposide in the treatment of newly diagnosed PML/RAR?-positive APL patients.