Original Manuscript
Leukemia (2005) 19, 2082–2089. doi:10.1038/sj.leu.2403867; published online 25 August 2005
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
Y Perel1, A Auvrignon2, T Leblanc3, G Michel4, Y Reguerre5, J-P Vannier6, J-H Dalle7, V Gandemer8, C Schmitt9, F Méchinaud10, O Lejars11, C Piguet12, G Couillaud13, B Pautard14, J Landman-Parker2, I Thuret4, N Aladjidi1, A Baruchel3 and G Leverger2 for the Group LAME of the Société Française des Cancers de l'Enfant (SFCE), France
- 1Pediatric Onco-Hematology Unit, University Hospital, Bordeaux, France
- 2Pediatric Onco-Hematology Unit, University Hospital, Paris-Trousseau, France
- 3Pediatric Onco-Hematology Unit, University Hospital, Paris-St Louis, France
- 4Pediatric Onco-Hematology Unit, University Hospital, Marseille, France
- 5Pediatric Onco-Hematology Unit, St Denis La Réunion, France
- 6Pediatric Onco-Hematology Unit, University Hospital, Rouen, France
- 7Pediatric Onco-Hematology Unit, University Hospital, Lille, France
- 8Pediatric Onco-Hematology Unit, University Hospital, Rennes, France
- 9Pediatric Onco-Hematology Unit, University Hospital, Nancy, France
- 10Pediatric Onco-Hematology Unit, University Hospital, Nantes, France
- 11Pediatric Onco-Hematology Unit, University Hospital, Tours, France
- 12Pediatric Onco-Hematology Unit, University Hospital, Limoges, France
- 13Pediatric Onco-Hematology Unit, University Hospital, Dijon, France
- 14Pediatric Onco-Hematology Unit, University Hospital, Amiens, France
Correspondence: Professor Y Perel, Unité d'Onco-Hématologie, Département de Pédiatrie, Hôpital des Enfants, Groupe Hospitalier Pellegrin, Place Amélie Raba-Léon, 33076 Bordeaux-Cédex, France. Fax: +33 5 56 79 48 05; E-mail: yves.perel@chu-bordeaux.fr
Received 14 December 2004; Accepted 14 April 2005; Published online 25 August 2005.
Abstract
From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique 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 60
4 and 484%, 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 524% for non-allografted patients and 577% for allografted patients (P=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 (MT-) than in patients randomized for MT (77.68 vs 598%; P=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.
Keywords:
childhood, acute myeloid leukemia, dose intensification, bone marrow transplantation, maintenance therapy
