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.

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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 35 Issue 15 Pg. 1730-1736 (May 20 2017) ISSN: 1527-7755 [Electronic] United States
• PMID: 28339328 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Thionucleotides
• Mercaptopurine
• Methyltransferases
• thiopurine methyltransferase
• Thioguanine

Topics

• Administration, Oral
• Adolescent
• Adult
• Antimetabolites, Antineoplastic (administration & dosage)
• Child
• Child, Preschool
• Dairy Products
• Drug Administration Schedule
• Drug Monitoring (methods)
• Erythrocytes (metabolism)
• Female
• Food-Drug Interactions
• Humans
• Male
• Medication Adherence
• Mercaptopurine (administration & dosage)
• Methyltransferases (genetics, metabolism)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (blood, drug therapy)
• Thioguanine (blood)
• Thionucleotides (blood)
• Young Adult