AIDA (ALL-TRANS-RETINOIC ACID PLUS IDARUBICIN) IN NEWLY-DIAGNOSED ACUTE PROMYELOCYTIC LEUKEMIA - A -ITALIANO-MALATTIE-EMATOLOGICHE-MALIGNE-DELLADULTO (GIMEMA) PILOT-STUDY

From March 1993 to October 1993, 20 consecutive, newly diagnosed acute promyelocytic leukemia (APL) patients from 13 Italian institutions en tered in a pilot study named AIDA, combining all-trans retinoic acid ( ATRA) with idarubicin (IDA). ATRA was administered orally beginning on the first day of induction at the dosage of 45 mg/m(2)/d until comple te remission (CR), whereas IDA was administered intravenously at the d osage of 12 mg/m(2)/d on days 2, 4, 6, and 8 of the induction. Patient s who achieved CR were consolidated with 3 courses of chemotherapy wit hout ATRA; thereafter, they were followed up for molecular and hematol ogic CR. The median age was 35.3 years (range, 6.5 to 67.6 years); 8 p atients were males and 12 females; 4 had the hypogranular variant of A PL (M3v), and 4 (2 with M3v) presented with leukocyte counts greater t han or equal to 10,000/mu L. Molecular analysis for the promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) hybrid gene at d iagnosis was performed in 16 patients by means of reverse transcriptio n-polymerase chain reaction (RT-PCR) analysis, and all were RT-PCR(+) for the hybrid gene. In the remaining 4 patients, the cytogenetic stud y showed the presence of the t(15;17). After a median time of 36 days (range, 28 to 52 days) 18 (90%) patients achieved CR; the remaining 2 patients died 12 and 34 days after diagnosis from myocardial infarctio n caused by fungal myocarditis and from massive hemoptysis, respective ly. ATRA syndrome was observed in only 2 patients, and, after the prom pt discontinuation of ATRA and initiation of dexamethasone, both recov ered from the syndrome. However, after recovering, 1 patient achieved CR, whereas the other died at day 34 because of massive hemoptysis; ot her side effects were very limited. At recovery from the third consoli dation course, only 3 of 14 (21.4%) tested patients were RT-PCR(+) for the PML-RAR alpha hybrid gene. Of these, 2 relapsed shortly afterward s; however, in the last patient, the PML-RAR alpha disappeared at succ essive testing performed 2 months later. As of September 30, 1995, aft er a median follow-up period from diagnosis of 27 months (range, 24 to 31 months), the overall survival and event-free survival durations ar e 85% and 69%, respectively; moreover, 14 of 18 (78%) patients who ach ieved CR are still alive and in first molecular and hematologic CR. Of the 4 relapsed patients, 3 achieved a second GR with ATRA and, after further treatment, are now in molecular and hematologic CR after 4+, 1 6+, and 17+ months from the second CR. These results indicate that (1) the AIDA protocol is highly effective in treating APL; (2) after 3 co nsolidation courses, the majority of patients who achieved CR are RT-P CR(-) for the hybrid gene PML-RAR alpha; (3) the persistence of an RT- PCR positivity for the PML-RAR alpha hybrid gene after 3 consolidation courses is indicative of early relapse, thus these patients still req uire additional treatment. These results have prompted the Gruppo Ital iano Malattie Ematologiche, Maligne dell'Adulto (GIMEMA) to initiate, In cooperation with the Associazione Italiana di Ematologia ed Oncolog ia Pediatrica and some European Organization for Research and Treatmen t of Cancer (EORTC) centers, a new multicentric clinical trial named A IDA LAP 0493 for the treatment of adult and pediatric APL patients. Al l patients are considered eligible if APL diagnosis is confirmed with molecular or cytogenetic studies for PML-RAR alpha hybrid gene or t(15 ;17) and are enrolled to receive the same induction and consolidation therapy of th is pilot study. After consolidation, patients who are RT -PCR(-) for PML-RAR alpha hybrid gene are randomized to four arms, whe reas patients who are RT-PCR(+) after consolidation undergo, if eligib le, an allogeneic transplantation procedure. (C) 1996 by The American Society of Hematology.