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.
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.
Perel
Y
Y
Pediatric Onco-Hematology Unit, University Hospital, Bordeaux, France. yves.perel@chu-bordeaux.fr
Auvrignon
A
A
Leblanc
T
T
Michel
G
G
Reguerre
Y
Y
Vannier
J-P
JP
Dalle
J-H
JH
Gandemer
V
V
Schmitt
C
C
Méchinaud
F
F
Lejars
O
O
Piguet
C
C
Couillaud
G
G
Pautard
B
B
Landman-Parker
J
J
Thuret
I
I
Aladjidi
N
N
Baruchel
A
A
Leverger
G
G
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