Prevalence and Predictors of Non-Adherence to 6-Mercaptopurine (6MP) in Children with Acute Lymphoblastic Leukemia (ALL) - a Children's Oncology Group Study

• Published in: Blood 2008-11, Vol.112 (11), p.897-897
• Main Authors: Bhatia, Smita, Villaluna, Doojduen, Landier, Wendy, Schaible, Alexandra, Hageman, Lindsey, Hanby, Cara, Leisenring, Wendy, Hunger, Stephen P., Robison, Leslie L., Relling, Mary V., Wong, F. Lennie
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V112.11.897.897

Use of contemporary risk-based therapy in children with ALL has resulted in five-year survival rates exceeding 80%. Achievement of durable remissions requires a maintenance phase composed of oral administration of antimetabolites (6-mercaptopurine and methotrexate) for approximately two years. Previous studies have shown that low systemic exposure to oral 6MP adversely affects prognosis, thus emphasizing the critical need for therapeutic levels throughout maintenance. However, significant inter-patient variability in red cell thioguanine nucleotide (6TGN – a major metabolite of 6MP) concentrations exists, and could in part be related to failure to adhere to prescribed therapy. Non-adherence in pediatric ALL patients has been reported – however, small sample sizes and varying methods of assessment make it difficult to understand the magnitude of this problem. The purpose of our study was to describe adherence to oral 6MP in a large multi-ethnic cohort of children with ALL. Patients were eligible to participate if they were diagnosed with ALL at age less than 22 years, belonged to one of four ethnic/racial groups (Asian, African-American, Caucasian, or Hispanic), and had completed at least 24 weeks of maintenance therapy. We have restricted the current report to Caucasians, where we have completed our target accrual. To measure 6MP adherence, we used the Medication Event Management System (MEMS) and supplied each patient with a MEMS TrackCap. This electronic cap allowed the collection of real-time data by recording the date and time(s) when the 6MP bottle was opened over a 6-month period. The MEMS data was downloaded at the end of the 6-month study period. Patients/parents also completed a self-administered sociodemographic questionnaire. Longitudinal analysis was performed using the Generalized Estimating Equations. A total of 173 Caucasian patients provided 26,424 person-days of observation for 6MP adherence. The median age at diagnosis was 5 years (1 to 19), and at study participation was 6 years (range, 2 to 20); median time from diagnosis was 18.8 months, and from start of maintenance, 8.1 months; 67% were males. NCI criteria for high-risk disease were present in 42% of the patients. The median annual household income was between $50K and $75K; 79% of the mothers and 72% of the fathers had received education beyond high school. The median number of household members (including patient) was 4 (range, 2 to 10). Adherence was defined as the ratio of 6MP bo