title: 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 (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 48+/-4%, 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 52+/-4% for non-allografted patients and 57+/-7% 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 (77.6+/-8 vs 59+/-8%; 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.
authors.affiliation: Pediatric Onco-Hematology Unit, University Hospital, Bordeaux, France. yves.perel@chu-bordeaux.fr
authors.forename: Y
authors.initials: Y
authors.lastname: Perel
authors.forename: A
authors.initials: A
authors.lastname: Auvrignon
authors.forename: T
authors.initials: T
authors.lastname: Leblanc
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: Y
authors.initials: Y
authors.lastname: Reguerre
authors.forename: J-P
authors.initials: JP
authors.lastname: Vannier
authors.forename: J-H
authors.initials: JH
authors.lastname: Dalle
authors.forename: V
authors.initials: V
authors.lastname: Gandemer
authors.forename: C
authors.initials: C
authors.lastname: Schmitt
authors.forename: F
authors.initials: F
authors.lastname: Méchinaud
authors.forename: O
authors.initials: O
authors.lastname: Lejars
authors.forename: C
authors.initials: C
authors.lastname: Piguet
authors.forename: G
authors.initials: G
authors.lastname: Couillaud
authors.forename: B
authors.initials: B
authors.lastname: Pautard
authors.forename: J
authors.initials: J
authors.lastname: Landman-Parker
authors.forename: I
authors.initials: I
authors.lastname: Thuret
authors.forename: N
authors.initials: N
authors.lastname: Aladjidi
authors.forename: A
authors.initials: A
authors.lastname: Baruchel
authors.forename: G
authors.initials: G
authors.lastname: Leverger
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D024221:Antineoplastic Protocols / Q000592:standards*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D012074:Remission Induction; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome