AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance

All-trans-retinoic acid (ATRA) has greatly modified the prognosis of acute promyelocytic leukemia (APL); however, the role of maintenance in patients in molecular complete remission (CR) after consolidation treatment is still debated. From July 1993 to May 2000, 807 genetically proven newly diagnosed APL patients received ATRA+Idarubicin (AIDA), as induction, followed by 3 intensive consolidation courses. Thereafter, patients RT-PCR negative for the PML/RARA fusion gene, were randomised into 4 arms: oral 6-mercaptopurine and intramuscular methotrexate (arm 1); ATRA alone (arm 2); 3 months of arm1 alternating to 15 days of arm 2 (arm 3); no further therapy (arm 4). Starting from 02/1997, randomisation was limited to ATRA-containing arms only (arms 2 and 3). CR was achieved in 761/807 (94.3%) patients and 681 completed the consolidation program. Of these, 664 (97.5%) were evaluated for the PML/RARa fusion gene and 586/646 (90.7%) who tested RT-PCR negative were randomised to maintenance. The event free survival (EFS) estimate at 12 years was 68.9% (C.I. 95%: 66.4-71.4) and no differences in DFS at 12 years were observed among the maintenance arms