Maintenance therapy in childhood acute myeloid leukemia.
OBJECTIVE
To determine whether, after very intensive induction and consolidation therapy in childhood AML, further maintenance therapy (MT) confers any advantage.


METHODS
Three hundred-nine children with previously untreated AML were registered in the LAME 89/91 protocol. This three-cycle intensive regimen included an induction phase (mitoxantrone plus cytarabine) and, for non-allografted patients, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine. In the LAME 89 study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to be given or not MT after consolidation therapy.


RESULTS
Out of 309 patients, 276 (90%) achieved a complete remission. The overall survival (OS) and event-free survival at 6 years for all patients were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no further treatment than in patients randomized for MT (81% +/- 13% vs 58% +/- 15%; p = 0.04) whilst the 5-year disease-free survival was not significantly different (60% +/- 19% vs 50% +/- 15%; p = 0.25). The improvement of OS in MT-patients appeared to be related to a higher salvage rate after relapse.


CONCLUSIONS
Over 50% of patients can be cured of AML in childhood. In the context of a very short and drug-intensive regimen, low-dose MT, owing to the lack of improvement in disease control and the worsening of survival, should not be recommended. Over the past 20 years, the outcome of acute myeloid leukemia (AML) in children has improved substantially. In the eighties, complete remission (CR) was achieved in nearly 90% of patients but event-free survival (EFS) was poor. Myeloablative therapy followed by allogenic bone-marrow transplantation (allo BMT) from an HLA-identical sibling was demonstrated, in our experience, to be the treatment of choice for improving DFS in children with AML in first remission. The major issue was how best to maintain complete remission for patients without an HLA sibling donor. Whereas several groups continued to include low-dose MT and others decided to omit it, in 1991, our group undertook a prospective randomized trial (LAME 91 protocol), the main aim of which was to assess the efficacy of MT in addition to an intensive induction and consolidation chemotherapy. The main results have been published previously and are now updated and described in a higher number of patients.
Perel
Y
Y
Centres Hospitalo-Universitaires de Bordeaux, Paris-Trousseau, France.
Auvrignon
A
A
Leblanc
T
T
Michel
G
G
Vannier
J P
JP
Dalle
J H
JH
Gandemer
V
V
Schmitt
C
C
Mèchinaud
F
F
Lamagnere
J P
JP
Piguet
Ch
Ch
Couillaud
G
G
Pautard
B
B
Baruchel
A
A
Leverger
G
G
D000208:Acute Disease; D000677:Amsacrine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D002648:Child; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D015122:Mercaptopurine / Q000627:therapeutic use; D008942:Mitoxantrone / Q000008:administration & dosage; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors
D000677:Amsacrine; D003561:Cytarabine; D008942:Mitoxantrone; D015122:Mercaptopurine; D001215:Asparaginase