Nonadherence to Oral Mercaptopurine and Risk of Relapse in Hispanic and Non-Hispanic White Children With Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

Author:

Bhatia Smita1,Landier Wendy1,Shangguan Muyun1,Hageman Lindsey1,Schaible Alexandra N.1,Carter Andrea R.1,Hanby Cara L.1,Leisenring Wendy1,Yasui Yutaka1,Kornegay Nancy M.1,Mascarenhas Leo1,Ritchey A. Kim1,Casillas Jacqueline N.1,Dickens David S.1,Meza Jane1,Carroll William L.1,Relling Mary V.1,Wong F. Lennie1

Affiliation:

1. Smita Bhatia, Wendy Landier, Muyun Shangguan, Lindsey Hageman, Alexandra N. Schaible, Cara L. Hanby, and F. Lennie Wong, City of Hope, Duarte; Andrea R. Carter, David Geffen School of Medicine, University of California, Los Angeles; Jacqueline N. Casillas, University of California, Los Angeles; Leo Mascarenhas, University of Southern California Keck School of Medicine, Children's Hospital Los Angeles, Los Angeles, CA; Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Yutaka Yasui,...

Abstract

Purpose Systemic exposure to mercaptopurine (MP) is critical for durable remissions in children with acute lymphoblastic leukemia (ALL). Nonadherence to oral MP could increase relapse risk and also contribute to inferior outcome in Hispanics. This study identified determinants of adherence and described impact of adherence on relapse, both overall and by ethnicity. Patients and Methods A total of 327 children with ALL (169 Hispanic; 158 non-Hispanic white) participated. Medication event-monitoring system caps recorded date and time of MP bottle openings. Adherence rate, calculated monthly, was defined as ratio of days of MP bottle opening to days when MP was prescribed. Results After 53,394 person-days of monitoring, adherence declined from 94.7% (month 1) to 90.2% (month 6; P < .001). Mean adherence over 6 months was significantly lower among Hispanics (88.4% v 94.8%; P < .001), patients age ≥ 12 years (85.8% v 93.1%; P < .001), and patients from single-mother households (80.6% v 93.1%; P = .001). A progressive increase in relapse was observed with decreasing adherence (reference: adherence ≥ 95%; 94.9% to 90%: hazard ratio [HR], 4.1; 95% CI,1.2 to 13.5; P = .02; 89.9% to 85%: HR, 4.0; 95% CI, 1.0 to 15.5; P = .04; < 85%: HR. 5.7; 95% CI, 1.9 to 16.8; P = .002). Cumulative incidence of relapse (± standard deviation) was higher among Hispanics (16.5% ± 4.0% v 6.3% ± 2.2%; P = .02). Association between Hispanic ethnicity and relapse (HR, 2.6; 95% CI, 1.1 to 6.1; P = .02) became nonsignificant (HR, 1.8; 95% CI, 0.6 to 5.2; P = .26) after adjusting for adherence and socioeconomic status. At adherence rates ≥ 90%, Hispanics continued to demonstrate higher relapse, whereas at rates < 90%, relapse risk was comparable to that of non-Hispanic whites. Conclusion Lower adherence to oral MP increases relapse risk. Ethnic difference in relapse risk differs by level of adherence—an observation currently under investigation.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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