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

Abstract

Summary: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.

Reassessing autotransplantation for acute myeloid leukaemia in first remission – a matched pair analysis of autologous marrow vs peripheral blood stem cells

“…In a series of 108 patients treated at a single institution over 20 years it has been shown that autologous stem cell transplantation should be part of a global treatment approach, a change in the whole strategy after 1989 (high-dose anthracycline in induction, addition of a second consolidation course) has resulted in an increase in CR rate (90 vs 77%), a better compliance to autografting (76 vs 48%) and a better disease-free survival rate (48 vs 32%; P ¼ 0.04). 31 Some previous studies have been concerned about being able to obtain sufficient stem cells when harvesting marrow after intensive chemotherapy because up to 20% of patients may require platelet support for months after transplant. 13 Hence, the MRC study harvested stem cells before the last consolidation in spite of this inevitably increasing the risk of tainting with residual leukaemia cells.…”