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

Wendy Landier, Lindsey Hageman, Yanjun Chen, Nancy Kornegay, William E. Evans, Bruce C. Bostrom, Jacqueline Casillas, David S. Dickens, Anne L. Angiolillo, Glen Lew, Kelly W. Maloney, Leo Mascarenhas, A. Kim Ritchey, Amanda M. Termuhlen, William L. Carroll, Mary V. Relling, F. Lennie Wong, Smita Bhatia

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 6 107.1 v 220.6 6 121.6; P = .5), with dairy versus without (220.1 6 87.8 v 216.3 6 121.3; P =.7), or in the evening/night versus morning/ midday versus varying times (218.8 6 119.7 v 195.5 6 82.3 v 174.8 6 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.

Original languageEnglish (US)
Pages (from-to)1730-1736
Number of pages7
JournalJournal of Clinical Oncology
Volume35
Issue number15
DOIs
StatePublished - May 20 2017

Bibliographical note

Funding Information:
Supported in part by the National Cancer Institute Grants No. R01CA096670, U10CA098543, U10CA098413, U10CA095861, U10CA180886, U10CA180899, UG1CA189955, P30CA21765, and R37CA36401; and by the National Institute of General Medical Sciences Grant No. P50GM115279; the Children?s Oncology Group; the St. Baldrick?s Foundation; and the American Lebanese Syrian Associated Charities.

Publisher Copyright:
© 2017 by American Society of Clinical Oncology

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