Improved efficiency of remission induction facilitates autologous BMT harvesting and improves overall survival in adults with AML : 108 patients treated at a single institution

A hundred and eight patients less than 60 years old with de novo acute myeloid leukemia were treated between 1982 and 1994 by protocols including final intensification with a transplant using autologous bone marrow purged by mafosfamide in first remission in the absence of an HLA-matched sibling donor available for allograft. From 1989, we attempted to improve tumor control by using high-dose anthracyclines in induction, by increasing from one to two the number of consolidation courses pre-transplant and by introducing intermediate doses of cytarabine in the first consolidation course. The CR rate was 77% (33/43) before 1989 and 90% (59/65) after 1989 (P = 0.06). Forty-five out of the 59 patients (76%) who achieved CR after 1989 could undergo bone marrow grafting in CR1 vs 16/33 (48%) before 1989 (P = 0.01). In spite of the higher proportion of patients above 50 years after 1989 (32%) toxicity was mild and an adequate graft was obtained more frequently after one collection. The principal factor relating to improvement in graft feasibility was the post-1989 modification of induction and consolidation regimens. This improvement in graft feasibility was associated with a better disease-free survival (DFS) (48 +/- 7% vs 32 +/- 8%, P = 0.04) and overall survival (OS) (53 +/- 6% vs 30 +/- 7%, P = 0.007) at 5 years. By multivariate analysis four factors were associated with overall survival (OS): karyotype, white blood cell count at diagnosis, treatment regimen and bone marrow grafting in CR1. This global approach should be prospectively compared with intensive chemotherapy.