title: 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.
abstract: 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.
authors.affiliation: Unité d'Onco-Hématologie, Département de Pédiatrie, Hôpital des Enfants, Groupe Hospitalier Pellegrin, Centres Hospitalo-Universitaires de Bordeaux, France. yves.perel@chu-bordeaux.fr
authors.forename: Yves
authors.initials: Y
authors.lastname: Perel
authors.forename: Anne
authors.initials: A
authors.lastname: Auvrignon
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vannier
authors.forename: Gerard
authors.initials: G
authors.lastname: Michel
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nelken
authors.forename: Virginie
authors.initials: V
authors.lastname: Gandemer
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lamagnere
authors.forename: Lionel
authors.initials: L
authors.lastname: De Lumley
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
authors.forename: Gerard
authors.initials: G
authors.lastname: Couillaud
authors.forename: Gerard
authors.initials: G
authors.lastname: Schaison
authors.forename: Judith
authors.initials: J
authors.lastname: Landman-Parker
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thuret
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Dalle
authors.forename: Andre
authors.initials: A
authors.lastname: Baruchel
authors.forename: Guy
authors.initials: G
authors.lastname: Leverger
mesh_terms: 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
chemical_list: D000677:Amsacrine; D003561:Cytarabine; D008942:Mitoxantrone; D015122:Mercaptopurine; D001215:Asparaginase