Outcome in Children With Relapsed Acute Myeloid Leukemia After Initial Treatment With the French Leucémie Aiquë Myéloïde Enfant (LAME) 89/91 Protocol of the French Society of Pediatric Hematology and Immunology

Abstract

Purpose: After present first-line therapies for childhood acute myeloid leukemia (AML), nearly 40% of patients still relapse. The goals of this retrospective study were to determine whether these children could be treated successfully with a salvage regimen and to establish the optimal therapeutic strategy. Patients and Methods: In the multicentric, prospective, Leucémie Aiquë Myéloïde Enfant 89/91 protocol, 106 of the 308 children enrolled between 1988 and 1998 relapsed. Initial treatment after the first complete remission (CR1) had been allogenic HLA-identical bone marrow transplantation (BMT; n = 21) or chemotherapy (n = 85). Treatment procedures were scheduled according to the choice of each participating institution. Results: When reinduction therapy was attempted, second complete remission (CR2) was obtained in 71% of patients (68 of 96 patients). BMT was performed in 53 (78%) of these 68 patients (autograft, mainly harvested in CR1, n = 25; matched sibling-donor BMT, n = 12; or alternative-donor BMT, n = 16). The 5-year overall survival (OS) rate for all 106 patients was 33%, and the disease-free survival (DFS) rate for children in CR2 was 45%. Multivariate analysis of re-treated children showed that the 5-year OS was higher if the CR1 had been longer than 12 months compared with less than 12 months (54% v 24%, respectively; P = .001) and lower if maintenance therapy had been given after CR1 compared with chemotherapy without maintenance therapy or HLA-identical BMT (12% v 40% v 52%, respectively; P = .002). For patients attaining CR2, the 5-year DFS rate was not significantly different for matched sibling-donor BMT (60%), autograft (47%), or alternative-donor BMT (44%). Conclusion: After aggressive first-line therapy, one third of unselected, relapsing AML children could be cured. Further prospective trials are warranted to define the optimal reinduction regimen and megadose chemotherapy and to evaluate the late effects of these therapies.