6MP adherence in a multiracial cohort of children with acute lymphoblastic leukemia: a Children's Oncology Group study

Abstract

Durable remissions in children with acute lymphoblastic leukemia (ALL) require a 2-year maintenance phase that includes daily oral 6-mercaptopurine (6MP). Adherence to oral 6MP among Asian-American and African-American children with ALL is unknown. We enrolled 298 children with ALL (71 Asian Americans, 68 African Americans, and 159 non-Hispanic whites) receiving oral 6MP for the maintenance phase. Adherence was measured electronically for 39 803 person-days. Adherence declined from 95.0% (month 1) to 91.8% (month 5, P < .0001). Adherence rates were significantly (P < .0001) lower in Asian Americans (90.0% ± 4.9%) and African Americans (87.1% ± 4.4%), as compared with non-Hispanic whites (95.2% ± 1.3%). Race-specific sociodemographic characteristics helped explain poor adherence (African Americans: low maternal education [less than a college degree: 78.9%, vs at least college degree: 94.6%; P < .0001]; Asian Americans: low-income households [<$50 000: 84.5%, vs ≥$50 000: 96.7%; P = .04]; households without mothers as full-time caregivers [85.6%] vs households with mothers as full-time caregivers [97.2%; P = .05]). Adherence rate below 90% was associated with increased relapse risk (hazard ratio, 3.9; P = .01). Using an adherence rate <90% to define nonadherence, 20.5% of the participants were nonadherers. 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 trial was registered at www.clinicaltrials.gov as #NCT00268528.

Figure 1

Adherence rates. (A) Adherence rate for the entire cohort over the 5 months of observation. (B) Adherence rate over time according to race. Test for heterogeneity: P < .0001; Asian Americans vs non-Hispanic whites: P = .01; African Americans vs non-Hispanic whites: P < .0001; African Americans vs Asian Americans: P = .41. (C) Adherence rate over time according to annual household income (<$50 000 vs ≥$50 000). (D) Adherence rate over time according to household structure (single parent/single child; nuclear family; single parent/multiple children). Test for heterogeneity: P = .05; single parent/single child vs single parent/multiple children: P = .1; nuclear family vs single parent/single child: P = .04; nuclear family vs single parent/multiple children: P = .6. (E) Adherence rate over time according to presence/absence of mother as the full-time caregiver. (A-E) Presented on the plots are the 95% CIs of model estimates.

Figure 2

Multivariable regression models with adherence rates dichotomized at 75%, 80%, 85%, 90%, 95%. Adjusted for NCI risk group, 6MP dose-intensity, blast chromosomal abnormalities, race, and for time from initiation of maintenance to study entry.