Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Smita Bhatia1,*,
  2. Wendy Landier1,
  3. Lindsey Hageman1,
  4. Heeyoung Kim1,
  5. Yanjun Chen1,
  6. Kristine R. Crews2,
  7. William E. Evans2,
  8. Bruce Bostrom3,
  9. Jacqueline Casillas4,
  10. David S. Dickens5,
  11. Kelly W. Maloney6,
  12. Joseph P. Neglia7,
  13. Yaddanapudi Ravindranath8,
  14. A. Kim Ritchey9,
  15. F. Lennie Wong1, and
  16. Mary V. Relling2
  1. 1 City of Hope, Duarte, CA, United States;
  2. 2 St. Jude Children's Research Hospital, Memphis, TN, United States;
  3. 3 Children's Hospitals and Clinics of Minnesota, Minneapolis, MN, United States;
  4. 4 David Geffen School of Medicine at UCLA, Los Angeles, CA, United States;
  5. 5 Helen DeVos Children's Hospital at Spectrum Health/Spectrum Health at Butterworth Campus, Grand Rapids, MI, United States;
  6. 6 University of Colorado School of Medicine, Aurora, CO, United States;
  7. 7 University of Minnesota Medical School, Minneapolis, MN, United States;
  8. 8 Children's Hospital of Michigan, Detroit, MI, United States;
  9. 9 Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States
  1. * Corresponding author; email: sbhatia{at}

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).


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, identifier: NCT00268528.

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