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J Clin Oncol. 2017 May 20;35(15):1730-1736. doi: 10.1200/JCO.2016.71.7579. Epub 2017 Mar 24.

Mercaptopurine Ingestion Habits, Red Cell Thioguanine Nucleotide Levels, and Relapse Risk in Children With Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group Study AALL03N1.

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Wendy Landier, Lindsey Hageman, Yanjun Chen, and Smita Bhatia, University of Alabama at Birmingham, Birmingham, AL; Nancy Kornegay, William E. Evans, and Mary V. Relling, St. Jude Children's Research Hospital, Memphis, TN; Bruce C. Bostrom, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN; Jacqueline Casillas, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; Leo Mascarenhas and Amanda M. Termuhlen, Children's Hospital Los Angeles, Los Angeles; F. Lennie Wong, City of Hope, Duarte, CA; David S. Dickens, Helen DeVos Children's Hospital at Spectrum Health/Spectrum Health at Butterworth Campus, Grand Rapids, MI; Anne L. Angiolillo, The George Washington School of Medicine, Washington, DC; Glen Lew, Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Kelly W. Maloney, University of Colorado School of Medicine, Aurora, CO; A. Kim Ritchey, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA; and William L. Carroll, Perlmutter Cancer Center, New York University-Langone Medical Center, New York, NY.


Purpose Children with acute lymphoblastic leukemia (ALL) are generally instructed to take mercaptopurine (6-MP) in the evening and without food or dairy products. This study examines the association between 6-MP ingestion habits and 6-MP adherence, red cell thioguanine nucleotide (TGN) levels, and risk of relapse in children with TMPT wild-type genotype. Methods Participants included 441 children with ALL receiving oral 6-MP for maintenance. Adherence was monitored over 48,086 patient-days using the Medication Event Monitoring System; nonadherence was defined as adherence rate < 95%. 6-MP ingestion habits examined included: takes 6-MP with versus never with food, takes 6-MP with versus never with dairy, and takes 6-MP in the evening versus morning versus varying times. Results Median age at study was 6 years (range, 2 to 20 years); 43.8% were nonadherent. Certain 6-MP ingestion habits were associated with nonadherence (taking 6-MP with dairy [odds ratio (OR), 1.9; 95% CI, 1.3 to 2.9; P = .003] and at varying times [OR, 3.4; 95% CI, 1.8 to 6.3; P = .0001]). After adjusting for adherence and other prognosticators, there was no association between 6-MP ingestion habits and relapse risk (6-MP with food: hazard ratio [HR], 0.7; 95% CI, 0.3 to 1.9; P = .5; with dairy: HR, 0.3; 95% CI, 0.07 to 1.5; P = .2; taken in evening/night: HR, 1.1; 95% CI, 0.2 to 7.8; P = .9; at varying times: HR, 0.3; 95% CI, 0.04 to 2.7; P = .3). Among adherent patients, there was no association between red cell TGN levels and taking 6-MP with food versus without (206.1 ± 107.1 v 220.6 ± 121.6; P = .5), with dairy versus without (220.1 ± 87.8 v 216.3 ± 121.3; P =.7), or in the evening/night versus morning/midday versus varying times (218.8 ± 119.7 v 195.5 ± 82.3 v 174.8 ± 93.4; P = .6). Conclusion Commonly practiced restrictions surrounding 6-MP ingestion might not influence outcome but may hinder adherence. Future recommendations regarding 6-MP intake during maintenance therapy for childhood ALL should aim to simplify administration.

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