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.

• 影响指数: 50.717
• 发表时间: May 2017 20
• 来源期刊: J Clin Oncol
• DOI: 10.1200/JCO.2016.71.7579
• PMID: 28339328
• 文章类型: Journal Article
• 中科院分区: Q1
• 方向: 医学
• 作者列表: Landier W,Hageman L,Chen Y,Kornegay N,Evans WE,Bostrom BC,Casillas J,Dickens DS,Angiolillo AL,Lew G,Maloney KW,Mascarenhas L,Ritchey AK,Termuhlen AM,Carroll WL,Relling MV,Wong FL,Bhatia S

Mesh: 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

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.