title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Lower adherence to oral MP increases relapse risk. Ethnic difference in relapse risk differs by level of adherence-an observation currently under investigation.
authors.affiliation: City of Hope, Duarte, CA 91010-3000, USA. sbhatia@coh.org
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
authors.forename: Wendy
authors.initials: W
authors.lastname: Landier
authors.forename: Muyun
authors.initials: M
authors.lastname: Shangguan
authors.forename: Lindsey
authors.initials: L
authors.lastname: Hageman
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Schaible
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Carter
authors.forename: Cara L
authors.initials: CL
authors.lastname: Hanby
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Kornegay
authors.forename: Leo
authors.initials: L
authors.lastname: Mascarenhas
authors.forename: A Kim
authors.initials: AK
authors.lastname: Ritchey
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Casillas
authors.forename: David S
authors.initials: DS
authors.lastname: Dickens
authors.forename: Jane
authors.initials: J
authors.lastname: Meza
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
authors.forename: F Lennie
authors.initials: FL
authors.lastname: Wong
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D007223:Infant; D008297:Male; D055118:Medication Adherence; D015122:Mercaptopurine / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000208:ethnology; D012008:Recurrence; D012306:Risk; D011795:Surveys and Questionnaires; D013997:Time Factors; D014481:United States
chemical_list: D015122:Mercaptopurine