Early Allogeneic Bone Marrow Transplantation for Young Adults with Acute Myeloid Leukemia in First Complete Remission: The 17 Year Experience of the BGMT Group.

Background. From 1984 and during 17 years, the BGMT inter-group prospectively followed the same strategy of early allogeneic bone marrow transplantation (alloBMT) compared to non allogeneic treatment in 4 consecutive trials, as modality of consolidation for patients (pts) under 45 with an HLA identical sibling donor in first complete remission (CR) of an acute myeloid leukemia (AML). The purpose of this study was to evaluate this strategy by an intent to treat analysis based on donor availability.

Pts and methods. In each of these trials, pts received an induction by daunorubicine 60 mg/m2/d 3d + cytarabine 100 mg/m2/d (CI) 10 d. followed by a light consolidation based on cytarabine 50 mg/m2/12h SC 7d + daunorubicine 60 mg/m2/d 2d. Pts under 45 with a sibling donor had an alloBMT (cyclophosphamide 60 mg/kg IV 2d + fractionated TBI 12 Gy) without any further chemotherapy. If not, pts were treated according to a strategy of chemotherapy which evolved the years according to experience and knowledge. The 182 pts with a donor were compared to the 290 who had not. The median age of these pts (M/F = 103/79 vs 154/136) was 34 vs 33.5 years (15–45). Median WBC count was 15 vs 16 (0.2–35) and WBC was ? 30 109/L for 65 vs 94 pts. The FAB distribution was: M1/M2 = 92 vs 150; M3 = 10 vs 14; M4/M5 = 63 vs 110; M0/M6/M7 = 17 vs 16. The cytogenetics risk groups distribution was: low risk = 32 vs 62 (24 vs 28%); intermediate risk = 78 vs 127 (58 vs 57%); high risk = 24 vs 34 (18 vs 15%). CR was achieved in 2 courses for 19 vs 42 pts (10 vs 14 %).

Results. AlloBMT was done for 90.7% of the eligible pts. With a median follow-up of 114 months, 10-year cumulative incidence of relapse and non relapse death, overall survival and leukemia free survival (LFS) were 27.2% vs 54.5% (p < .001), 24.4% vs 5.6% (p < .001), 51.2% vs 43.4% (p = .11), and 48.3% vs 39.9% (p < .03), respectively. For all patients, univariate and multivariate analysis found that initial WBC count, FAB subtypes, cytogenetic risk group, number of course to achieve CR, demonstrated a significant prognosis influence. A better LFS was observed in the donor group among patients with M1 to M5 FAB subtypes (52.4% vs 41.9% (p < .01)), among those with WBC > 30 109/L (47.3% vs 30.7% (p < .02)), and among those of the intermediate cytogenetic risk group (58% vs 43% (p < .01)). For low cytogenetic risk group no difference was shown between donor an no donor group (58.6% vs 65.9% (p =.63). In this study, alloBMT presents limitations in the most aggressive diseases such as M0/M6/M7 FAB subtypes (11.8% vs 6.3% (p = .15)) or high cytogenetic risk group (12.5% vs 7.8% (p = .67). In this situation it does not seem to be sufficient enough to control disease by the graft versus leukemia effect alone. For these pts new investigations should be undertaken.