A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission: a report from the Children's Cancer Group

Abstract

Intensive, myelosuppressive therapy is necessary to maximize outcomes for patients with acute myeloid leukemia (AML). A comparison was made of 3 aggressive postremission approaches for children and adolescents with AML in a randomized trial, CCG-2891. A total of 652 children and adolescents with AML who achieved remission on 2 induction regimens using identical drugs and doses (standard and intensive timing) were eligible for allocation to allogeneic bone marrow transplantation (BMT) based on matched related donor status (n ‫؍‬ 181) or randomization to autologous BMT (n ‫؍‬ 177) or to aggressive high-dose cytarabine-based chemotherapy (n ‫؍‬ 179).Only 115 patients (18%) refused to participate in the postremission phase of this study. Overall compliance with the 3 allocated regimens was 90%. At 8 years actuarial, 54% ؎ 4% (95% confidence interval) of all remission patients remain alive. Survival by assigned regimen ("intent to treat") is as follows: allogeneic BMT, 60% ؎ 9%; autologous BMT, 48% ؎ 8%; and chemotherapy, 53% ؎ 8%. Survival in the allogeneic BMT group is significantly superior to autologous BMT (P ‫؍‬ .002) and chemotherapy (P ‫؍‬ .05); differences between chemotherapy and autologous BMT are not significant (P ‫؍‬ .

Autologous purified peripheral blood SCT in childhood low-risk relapsed ALL

“…50,51 For children undergoing allogeneic transplantation the same TBI-related side effects are expected as in the autologous setting, but amplified by immunological complications, that is GVHD and infections because of highly impaired immune reconstitution, which are expected to increase treatment-related mortality and long-term side effects. 50,54,[58][59][60][61] An allogeneic approach could be adopted for children who experience relapse after autologous transplant, such as the eight patients in this series, of whom four were rescued and are in long-term CR3.…”

Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation? – An American view

“…Paediatric cooperative group trials prospectively designed to compare allogeneic BMT with chemotherapy and ⁄ or autologous BMT (Vowels et al, 1992;Amadori et al, 1993;Nesbit et al, 1994;Shaw et al, 1994;Wells et al, 1994;Ravindranath et al, 1996;Stevens et al, 1998;Woods et al, 2001a) are summarized in Table I. In order for this approach to eliminate selection bias, HLA typing must be handled as precisely as randomization of a patient in a conventional prospective randomized trial.…”

“…trials have compared autologous BMT with consolidation chemotherapy and found no DFS advantage (Amadori et al, 1993;Ravindranath et al, 1996;Stevens et al, 1998;Woods et al, 2001a).…”

“…Because outcomes of patients treated in the recent, more intensive, chemotherapy studies (Stevens et al, 1998;Woods et al, 2001a) appear to be superior to their predecessors, it may not be appropriate to pool the results of the best chemotherapy with those of less successful programmes. Any meta-analysis would have to account for this.…”

“…Any meta-analysis would have to account for this. However, analysing separately the intensively timed induction arm of the Children's Cancer Group (CCG) protocol CCG 2891, which produced strikingly improved results relative to less intensive induction therapy (Woods et al, 1996(Woods et al, , 2001a, the significant superiority of survival after allogeneic BMT persists. Even in the successful British Medical Research Council (MRC) AML10 trial, survival after allogeneic BMT was superior, with P ¼ 0AE10 (Stevens et al, 1998).…”