TY - JOUR
T1 - Mercaptopurine ingestion habits, red cell thioguanine nucleotide levels, and relapse risk in children with acute Lymphoblastic Leukemia
T2 - A report from the children’s Oncology group study AALL03N1
AU - Landier, Wendy
AU - Hageman, Lindsey
AU - Chen, Yanjun
AU - Kornegay, Nancy
AU - Evans, William E.
AU - Bostrom, Bruce C.
AU - Casillas, Jacqueline
AU - Dickens, David S.
AU - Angiolillo, Anne L.
AU - Lew, Glen
AU - Maloney, Kelly W.
AU - Mascarenhas, Leo
AU - Ritchey, A. Kim
AU - Termuhlen, Amanda M.
AU - Carroll, William L.
AU - Relling, Mary V.
AU - Wong, F. Lennie
AU - Bhatia, Smita
N1 - 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
PY - 2017/5/20
Y1 - 2017/5/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2016.71.7579
DO - 10.1200/JCO.2016.71.7579
M3 - Article
C2 - 28339328
AN - SCOPUS:85022201488
SN - 0732-183X
VL - 35
SP - 1730
EP - 1736
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15
ER -
