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Mercaptopurine Ingestion Habits, Red Cell Thioguanine Nucleotide Levels, and Relapse Risk in Children With Acute
Wendy Landier1, Lindsey Hageman1, Yanjun Chen1
1Wendy 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.
Abstract:
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.
