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

Author(s):Show less -

Brandalise, Silvia R. ^[1] ; Pinheiro, Vitoria R. ; Aguiar, Simone S. ; Matsuda, Eduardo I. ; Otubo, Rosemary ; Yunes, Jose 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.

Affiliation

^[1] Univ Estadual Campinas, Serv Hematol Oncol Pediat, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: Journal of Clinical Oncology; v. 28, n. 11, p. 1911-1918, APR 10 2010.
• Web of Science Citations: 44

Abstract

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 (MIX) 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-ME/MIX (group 1, n 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MIX (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 MIX 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. (AU)

• FAPESP's process: 01/13206-9 - Gene expression profiles associated with chemotherapy in acute lymphoid leukemia of childhood
• Grantee: Luiz Gonzaga Tone
• Support Opportunities: Genome Research Grants