Changes in Cardiac Biomarkers During Doxorubicin Treatment of Pediatric Patients With High-Risk Acute Lymphoblastic Leukemia: Associations With Long-Term Echocardiographic Outcomes

Steven E Lipshultz; Tracie L Miller; Rebecca E Scully; Stuart R Lipsitz; Nader Rifai; Lewis B Silverman; Steven D Colan; Donna S Neuberg; Suzanne E Dahlberg; Jacqueline M Henkel; Barbara L Asselin; Uma H Athale; Luis A Clavell; Caroline Laverdière; Bruno Michon; Marshall A Schorin; Stephen E Sallan

doi:10.1200/JCO.2010.30.3404

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Changes in Cardiac Biomarkers During Doxorubicin Treatment of Pediatric Patients With High-Risk Acute Lymphoblastic Leukemia: Associations With Long-Term Echocardiographic Outcomes

Journal article

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Changes in Cardiac Biomarkers During Doxorubicin Treatment of Pediatric Patients With High-Risk Acute Lymphoblastic Leukemia: Associations With Long-Term Echocardiographic Outcomes

Steven E Lipshultz, Tracie L Miller, Rebecca E Scully, Stuart R Lipsitz, Nader Rifai, Lewis B Silverman, Steven D Colan, Donna S Neuberg, Suzanne E Dahlberg, Jacqueline M Henkel, …

Journal of clinical oncology, Vol.30(10), pp.1042-1049

2012-04-01

DOI: https://doi.org/10.1200/JCO.2010.30.3404

PMCID: PMC3341148

PMID: 22370326

Abstract

Purpose Doxorubicin causes cardiac injury and cardiomyopathy in children with acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might help individualize treatment by immediately identifying cardiac injury and cardiomyopathy. Patients and Methods Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C-reactive protein (hsCRP; inflammatory biomarker) were obtained before, during, and after treatment. Results cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP levels were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment (P = .07). The percentage of children with increased hsCRP levels did not differ between groups at any time. In the first 90 days of treatment, detectable increases in cTnT were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness 4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01). Increases in hsCRP were not associated with any echocardiographic variables. Conclusion cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity in children with high-risk ALL. Definitive validation studies are required to fully establish their range of clinical utility.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.219 Cancer Drugs; 1.219.1342 Cardiotoxicity
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Changes in Cardiac Biomarkers During Doxorubicin Treatment of Pediatric Patients With High-Risk Acute Lymphoblastic Leukemia: Associations With Long-Term Echocardiographic Outcomes
Creators: Steven E Lipshultz - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Tracie L Miller - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Rebecca E Scully - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Stuart R Lipsitz - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Nader Rifai - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Lewis B Silverman - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Steven D Colan - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Donna S Neuberg - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Suzanne E Dahlberg - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Jacqueline M Henkel - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Barbara L Asselin - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Uma H Athale - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Luis A Clavell - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Caroline Laverdière - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Bruno Michon - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Marshall A Schorin - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Stephen E Sallan - Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, and Jacqueline M. Henkel, University of Miami Miller School of Medicine; Steven E. Lipshultz and Tracie L. Miller, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Stuart R. Lipsitz, Brigham and Women's Hospital; Nader Rifai, Harvard Medical School; Lewis B. Silverman, Donna S. Neuberg, Suzanne E. Dahlberg, and Stephen E. Sallan, Dana-Farber Cancer Institute, Harvard Medical School; Lewis B. Silverman and Stephen E. Sallan
Publication Details: Journal of clinical oncology, Vol.30(10), pp.1042-1049
Academic Unit: UMMG Department of Pediatrics
Language: English
Resource Type: Journal article
PMID: 22370326
PMCID: PMC3341148
Record Identifier: 991031577150102976