Impact of addition of maintenance therapy to intensive induction and consolidation chemotherapy for childhood acute myeloblastic leukemia: results of a prospective randomized trial, LAME 89/91. Leucámie Aiqüe Myéloïde Enfant.
OBJECTIVE
To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML).


METHODS
A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT.


RESULTS
A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% +/- 19% v 50% +/- 15%; P =.25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% +/- 13% v 58% +/- 15%; P =.04) due to a higher salvage rate after relapse.


CONCLUSIONS
More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.
Perel
Yves
Y
Unité d'Onco-Hématologie, Département de Pédiatrie, Hôpital des Enfants, Groupe Hospitalier Pellegrin, Centres Hospitalo-Universitaires de Bordeaux, France. yves.perel@chu-bordeaux.fr
Auvrignon
Anne
A
Leblanc
Thierry
T
Vannier
Jean-Pierre
JP
Michel
Gerard
G
Nelken
Brigitte
B
Gandemer
Virginie
V
Schmitt
Claudine
C
Lamagnere
Jean-Pierre
JP
De Lumley
Lionel
L
Bader-Meunier
Brigitte
B
Couillaud
Gerard
G
Schaison
Gerard
G
Landman-Parker
Judith
J
Thuret
Isabelle
I
Dalle
Jean-Hugues
JH
Baruchel
Andre
A
Leverger
Guy
G
D000677:Amsacrine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008942:Mitoxantrone / Q000008:administration & dosage; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome
D000677:Amsacrine; D003561:Cytarabine; D008942:Mitoxantrone; D015122:Mercaptopurine; D001215:Asparaginase