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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

From the Centres Hospitalo-Universitaires de Bordeaux, Paris-Trousseau, Paris-St Louis, Rouen, Marseille, Lille, Rennes, Nancy, Tours, Limoges, Paris Bicetre, and Dijon, France.

Address reprint requests to Yves Perel, MD, Unité d’Onco-Hématologie, Département de Pédiatrie, Hôpital des Enfants, Groupe Hospitalier Pellegrin, Place Amélie Raba-Léon, 33076 Bordeaux Cédex, France; email: yves.perel{at}chu-bordeaux.fr

PURPOSE: 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).

PATIENTS AND 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.

CONCLUSION: 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.

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