Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Abstract

From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucé mie Aiguë Myé loblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 6074 and 4874%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 5274% for non-allografted patients and 5777% for allografted patients (P ¼ NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MTÀ) than in patients randomized for MT (77.678 vs 5978%; P ¼ 0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.

Improved treatment results for childhood acute myeloid leukemia in Taiwan

“…The 5-year EFS of 5474.4% achieved in studies TPOG-AML-97A, TPOG-APL-97, and TPOG-APL-2001 were at least comparable to the 31-54% attained in studies conducted in other developed countries during the same era, [25][26][27][28][29][30][31][32][33][34][35][36][37] and the treatment was well tolerated. However, like in the Dutch Childhood Oncology Group experience, a more effective, but less toxic, therapy and better supportive care guidelines for childhood AML are still needed.…”

“…[25][26][27][28][29][30][31][32][33][34][35][36][37] The challenge now is to extend the benefits of contemporary AML therapy to larger numbers of patients in developing countries, where fewer than 10% children with acute leukemia are receiving protocol-based therapy. 59 …”

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

“…Table 2 shows that patients with MLL-rearranged AML have an intermediate outcome, with a 5y-pEFS (probability of EFS at 5 years from diagnosis) ranging from 32 to 54% and a 5y-pOS (probability of OS at 5 years from diagnosis) ranging from 42 to 62%. 4,5,[69][70][71][72][73][74][75][76][77] Currently, hematopoietic stem cell transplantation is no longer advised in first remission. Recently, we identified the t(1;11)(q21;q23) subgroup as a new prognostic subgroup in pediatric AML.…”

Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study

“…Patients were treated in accordance with current protocol at the time of leukemia diagnosis, depending on AL type (AML or ALL; that is, FRench group for childhood ALL (FRALLE), European Organisation for Research and Treatment of Cancer (EORTC), Leucémie Aiguë Myéloblastique Enfant (LAME) or ELAM). [19][20][21][22][23] Overall, 16 patients underwent central nervous system irradiation.…”