Benefits of the Intermittent Use of 6-Mercaptopurine and Methotrexate in Maintenance Treatment for Low-Risk Acute Lymphoblastic Leukemia in Children: Randomized Trial From the Brazilian Childhood Cooperative Group—Protocol ALL-99

PURPOSE To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MTX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. PATIENTS AN...

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Published in:	Journal of clinical oncology Vol. 28; no. 11; pp. 1911 - 1918
Main Authors:	Brandalise, Silvia R, Pinheiro, Vitória R, Aguiar, Simone S, Matsuda, Eduardo I, Otubo, Rosemary, Yunes, José A, Pereira, Waldir V, Carvalho, Eny G, Cristofani, Lilian M, Souza, Marcelo S, Lee, Maria L, Dobbin, Jane A, Pombo-de-Oliveira, Maria S, Lopes, Luiz F, Melnikoff, Katharina N T, Brunetto, Algemir L, Tone, Luiz G, Scrideli, Carlos A, Morais, Vera L L, Viana, Marcos B
Format:	Journal Article
Language:	English
Published:	United States American Society of Clinical Oncology 10-04-2010
Subjects:	Adolescent Antineoplastic Combined Chemotherapy Protocols - therapeutic use Brazil Child Child, Preschool Female Humans Infant Male Mercaptopurine - administration & dosage Methotrexate - administration & dosage Neoplasm Staging Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Prospective Studies Risk Factors Survival Rate Treatment Outcome
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Summary:	PURPOSE To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MTX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. PATIENTS AND METHODS Between October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n = 544) were randomly allocated to receive either continuous 6-MP/MTX (group 1, n = 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MTX (200 mg/m(2) every 3 weeks; group 2, n = 272). RESULTS The 5-year overall survival (OS) and EFS were 92.5% +/- 1.5% SE and 83.6% +/- 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% +/- 2.2% SE (group 1) and 93.6% +/- 2.1% SE (group 2; P = .28) and EFS 80.9% +/- 3.2% SE (group 1) and 86.5% +/- 2.8% SE (group 2; P = .089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P = .027), while no difference was seen for girls (87.0% v 88.8% SE; P = .78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P = .002), and 772 and 636 for hematologic episodes (P = .005). Deaths on maintenance were: seven (group 1) and one (group 2). CONCLUSION The intermittent use of 6-MP and MTX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.
ISSN:	0732-183X 1527-7755
DOI:	10.1200/JCO.2009.25.6115