Factors associated with nonadherence to oral 6-mercaptopurine (6MP) in children with acute lymphoblastic leukemia (ALL): A report from Children's Oncology Group (COG) study AALL03N1

Background: We have previously shown that poor adherence (adherence rate <95%) to oral 6MP is prevalent in children with ALL, and increases relapse risk (JCO 30[17]:2094-101). However, behavioral predictors of non-adherence to oral 6MP have not been examined. Methods: We addressed this gap in 462 children (non-Hispanic Whites: 34%; Hispanics: 36%, Asians: 15%, African-Americans: 15%) with ALL diagnosed at age ≤21 years, and receiving maintenance therapy. 6MP adherence was measured over 6 months using Medication Event Management System (MEMS) that recorded dates/times of 6MP bottle opening (adherence rate=days bottle opened/days 6MP prescribed). A 37-item questionnaire assessed barriers/facilitators (addressing the Health Belief Model [HBM]) to adherence. Results: Median age at study was 6 years (2-20); 67% were males; 40% had high-risk disease. MEMS monitoring for 76,174 person-days yielded a non-adherence rate of 44.4%. Multivariable analysis identified the following predictors of non-adherence: i) age ≥12 years (Odds ratio [OR]=2.2, p=0.02); ii) Hispanic ethnicity (OR=2.1, p=0.005); iii) African-American race (OR=4.2, p<.001); iv) parental education ≤high school (OR=1.8, p=0.02); v) annual household income <$50,000 (OR=1.6, p=0.05); vi) involvement of ≥2 adults in 6MP supervision (OR=2.4; p=.004); vii) failure (on part of parents/patients) to understand the purpose of 6MP (OR=2.8; p<.001); viii) failure to take 6MP at the same time each day (OR=1.8; p<.01); and ix) taking 6MP with milk/dairy (OR=1.9; p=.03). Conclusions: In addition to sociodemographic predictors, we identified behavioral determinants of 6MP non-adherence that align with HBM. Lack of perceived benefits (not understanding the purpose of 6MP), absence of cues to action (not taking medication at same time each day), low self-efficacy (absence of a designated adult assuming primary responsibility for 6MP administration), and presence of barriers (dietary restrictions) contributed to non-adherence. These findings identify vulnerable populations that could benefit from targeted interventions to improve adherence in pediatric ALL. Clinical trial information: NCT00268528.