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

Smita Bhatia, Wendy Landier, Muyun Shangguan, Lindsey Hageman, Alexandra N. Schaible, Andrea R. Carter, Cara L. Hanby, Wendy Leisenring, Yutaka Yasui, Nancy M. Kornegay, Leo Mascarenhas, A. Kim Ritchey, Jacqueline N. Casillas, David S. Dickens, Jane L Meza, William L. Carroll, Mary V. Relling, F. Lennie Wong

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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.

Original languageEnglish (US)
Pages (from-to)2094-2101
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number17
DOIs
StatePublished - Jun 10 2012

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6-Mercaptopurine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hispanic Americans
Recurrence
Social Class
Mothers
Observation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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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. / Bhatia, Smita; Landier, Wendy; Shangguan, Muyun; Hageman, Lindsey; Schaible, Alexandra N.; Carter, Andrea R.; Hanby, Cara L.; Leisenring, Wendy; Yasui, Yutaka; Kornegay, Nancy M.; Mascarenhas, Leo; Ritchey, A. Kim; Casillas, Jacqueline N.; Dickens, David S.; Meza, Jane L; Carroll, William L.; Relling, Mary V.; Wong, F. Lennie.

In: Journal of Clinical Oncology, Vol. 30, No. 17, 10.06.2012, p. 2094-2101.

Research output: Contribution to journalArticle

Bhatia, S, Landier, W, Shangguan, M, Hageman, L, Schaible, AN, Carter, AR, Hanby, CL, Leisenring, W, Yasui, Y, Kornegay, NM, Mascarenhas, L, Ritchey, AK, Casillas, JN, Dickens, DS, Meza, JL, Carroll, WL, Relling, MV & Wong, FL 2012, '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', Journal of Clinical Oncology, vol. 30, no. 17, pp. 2094-2101. https://doi.org/10.1200/JCO.2011.38.9924
Bhatia, Smita ; Landier, Wendy ; Shangguan, Muyun ; Hageman, Lindsey ; Schaible, Alexandra N. ; Carter, Andrea R. ; Hanby, Cara L. ; Leisenring, Wendy ; Yasui, Yutaka ; Kornegay, Nancy M. ; Mascarenhas, Leo ; Ritchey, A. Kim ; Casillas, Jacqueline N. ; Dickens, David S. ; Meza, Jane L ; Carroll, William L. ; Relling, Mary V. ; Wong, F. Lennie. / 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. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 17. pp. 2094-2101.
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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.",
author = "Smita Bhatia and Wendy Landier and Muyun Shangguan and Lindsey Hageman and Schaible, {Alexandra N.} and Carter, {Andrea R.} and Hanby, {Cara L.} and Wendy Leisenring and Yutaka Yasui and Kornegay, {Nancy M.} and Leo Mascarenhas and Ritchey, {A. Kim} and Casillas, {Jacqueline N.} and Dickens, {David S.} and Meza, {Jane L} and Carroll, {William L.} and Relling, {Mary V.} and Wong, {F. Lennie}",
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TY - JOUR

T1 - Nonadherence to oral mercaptopurine and risk of relapse in hispanic and non-hispanic white children with acute lymphoblastic leukemia

T2 - A report from the Children's Oncology Group

AU - Bhatia, Smita

AU - Landier, Wendy

AU - Shangguan, Muyun

AU - Hageman, Lindsey

AU - Schaible, Alexandra N.

AU - Carter, Andrea R.

AU - Hanby, Cara L.

AU - Leisenring, Wendy

AU - Yasui, Yutaka

AU - Kornegay, Nancy M.

AU - Mascarenhas, Leo

AU - Ritchey, A. Kim

AU - Casillas, Jacqueline N.

AU - Dickens, David S.

AU - Meza, Jane L

AU - Carroll, William L.

AU - Relling, Mary V.

AU - Wong, F. Lennie

PY - 2012/6/10

Y1 - 2012/6/10

N2 - 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.

AB - 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.

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