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Adherence to oral 6-mercaptopurine in African American and Asian children with acute lymphoblastic leukemia: a Children's Oncology Group study

Smita Bhatia, Wendy Landier, Lindsey Hageman, Heeyoung Kim, Yanjun Chen, Kristine R. Crews, William E. Evans, Bruce Bostrom, Jacqueline Casillas, David S. Dickens, Kelly W. Maloney, Joseph P. Neglia, Yaddanapudi Ravindranath, A. Kim Ritchey, F. Lennie Wong and Mary V. Relling

Key points

  • Adherence to 6MP at <90% was associated with a 3.1-fold increased risk of relapse in a multiracial cohort of children with ALL.

  • 46% of African Americans and 28% of Asians as compared with 14% of non-Hispanic whites were non-adherers (p<0.0001).

Abstract

Durable remissions in children with acute lymphoblastic leukemia (ALL) require a two-year maintenance phase that includes daily oral 6-mercaptopurine (6MP). Adherence to oral 6MP among Asian and African American children with ALL is unknown. We enrolled 298 children with ALL (71 Asians, 68 African Americans, and 159 non-Hispanic whites) receiving oral 6MP for the maintenance phase. Adherence was measured electronically using Medication Event Monitoring System for 39,794 person-days. Adherence declined from 94.8% (Month 1) to 91.3% (Month 5, p<0.0001). Adherence rates were significantly (p<0.0001) lower in Asians (86.1%±3.1%) and African Americans (86.4%±2.4%), as compared with non-Hispanic whites (95.8%±0.6%). Race-specific sociodemographic characteristics helped explain poor adherence (African Americans: low maternal education, single-parent/multiple-children households; Asians: low-income households; both Asians and African Americans: households without mothers as full-time caregivers). Adherence rate below 90% was associated with increased relapse risk (hazard ratio, 3.1, p=0.04). Using adherence rate <90% to define non-adherence, 46% of African Americans and 28% of Asians as compared with 14% of non-Hispanic whites were non-adherers (p<0.0001). Moreover, 31% of relapses were attributable to non-adherence. We identify race-specific determinants of adherence, and define a clinically-relevant level of adherence needed to minimize relapse risk in a multiracial cohort of children with ALL. This study was registered at ClinicalTrials.gov, identifier: NCT00268528.

  • Submitted January 27, 2014.
  • Accepted April 30, 2014.