急性淋巴细胞白血病患儿的巯嘌呤摄入习惯、红细胞硫鸟嘌呤核苷酸水平与复发风险：儿童肿瘤研究组AALL03N1研究报告
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.
作者信息
Landier Wendy, Hageman Lindsey, Chen Yanjun, Kornegay Nancy, Evans William E, Bostrom Bruce C, Casillas Jacqueline, Dickens David S, Angiolillo Anne L, Lew Glen, Maloney Kelly W, Mascarenhas Leo, Ritchey A Kim, Termuhlen Amanda M, Carroll William L, Relling Mary V, Wong F Lennie, Bhatia Smita
机构信息
Wendy 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.
出版信息
J Clin Oncol. 2017 May 20;35(15):1730-1736. doi: 10.1200/JCO.2016.71.7579. Epub 2017 Mar 24.
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.
目的 通常指导急性淋巴细胞白血病（ALL）患儿在晚上服用巯嘌呤（6-MP），且不与食物或乳制品同服。本研究探讨6-MP服用习惯与6-MP依从性、红细胞硫鸟嘌呤核苷酸（TGN）水平以及TMPT野生型基因型患儿复发风险之间的关联。方法 参与者包括441例接受口服6-MP维持治疗的ALL患儿。使用药物事件监测系统在48086个患者日监测依从性；不依从定义为依从率<95%。所研究的6-MP服用习惯包括：是否与食物同服、是否与乳制品同服以及在晚上、早上还是不同时间服用。结果 研究时的中位年龄为6岁（范围2至20岁）；43.8%的患儿不依从。某些6-MP服用习惯与不依从相关（与乳制品同服[比值比（OR），1.9；95%置信区间（CI），1.3至2.9；P = 0.003]以及在不同时间服用[OR，3.4；95%CI，1.8至6.3；P = 0.0001]）。在调整依从性和其他预后因素后，6-MP服用习惯与复发风险之间无关联（与食物同服：风险比[HR]，0.7；95%CI，0.3至1.9；P = 0.5；与乳制品同服：HR，0.3；95%CI，0.07至1.5；P = 0.2；在晚上/夜间服用：HR，1.1；95%CI，0.2至7.8；P = 0.9；在不同时间服用：HR，0.3；95%CI，0.04至2.7；P = 0.3）。在依从性好的患者中，红细胞TGN水平与是否与食物同服（206.1±107.1对220.6±121.6；P = 0.5）、是否与乳制品同服（220.1±87.8对216.3±121.3；P = 0.7）或在晚上/夜间、早上/中午还是不同时间服用（218.8±119.7对195.5±82.3对174.8±93.4；P = 0.6）均无关联。结论 围绕6-MP服用的常见限制可能不影响治疗结果，但可能会妨碍依从性。未来关于儿童ALL维持治疗期间6-MP摄入的建议应旨在简化给药方式。
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