Predictors of non-adherence to oral chemotherapy in children with acute lymphoblastic leukemia

Abstract

Overall survival for pediatric patients with acute lymphoblastic leukemia (A.L.L.) treated with contemporary therapy now exceeds 85%; however, approximately 20% will experience relapse. Since A.L.L. is the most common malignancy in children, relapsed patients comprise a large proportion of the total number of children with cancer. The prognosis for long-term survival following relapse is generally poor; thus, relapsed A.L.L. is a significant contributor to cancer-related mortality in children. Poor adherence to oral medication is a substantial problem in contemporary health care and may contribute to unexplained relapses in children with A.L.L. Therapy for pediatric A.L.L. includes a prolonged "maintenance" phase that requires daily 6-mercaptopurine (6MP), a self-or parent/caregiver-administered oral chemotherapy agent given for approximately two years. 6MP has been shown to be a critical component of the curative regimen for A.L.L.; thus, children with A.L.L. who fail to adhere to oral 6MP chemotherapy as prescribed may be at increased risk of leukemia relapse. This study used extant questionnaire data from a cohort of children with A.L.L enrolled on a Children's Oncology Group study (AALL03N1) to determine the prevalence of self/parent-reported non-adherence to oral 6MP during the maintenance phase of A.L.L. therapy, and to identify sociodemographic and behavioral predictors of non-adherence to oral 6MP. Twenty-two percent of children in the cohort were non-adherent to oral chemotherapy, defined as missing more than one dose of 6MP for non-medical reasons over the 112-day observation period. The risk of non-adherence was significantly increased for those who failed to perceive the severity of the child's illness (Odds ratio [OR] 1.89, 95% Confidence Interval [CI] 1.00-3.55, P=0.049) or the benefits of treatment with oral 6MP (OR 1.78, 95%CI 1.07-2.94, P=0.025). Vulnerable subgroups included Hispanic ethnicity (OR 2.25, 95%CI 1.30-3.90, P=0.004) and older age (OR 1.07 per year, 95%CI 1.02-1.12, P=0.005). Study findings suggest that even occasional reports of missed 6MP doses may herald a significant adherence problem; that patients and their parents may need ongoing reminders regarding the subclinical and asymptomatic nature of leukemia in remission; and that frequent review with families regarding the purpose, function, and proper administration of oral 6MP is imperative.