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 Laverdier̀e, Bruno Michon, Marshall A. Schorin, Stephen E. Sallan

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1042-1049
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number10
DOIs
StatePublished - Apr 1 2012

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Doxorubicin
Biomarkers
Pediatrics
Dexrazoxane
Cardiomyopathies
Therapeutics
Wounds and Injuries
Troponin T
Ventricular Remodeling
Validation Studies
Brain Natriuretic Peptide
C-Reactive Protein
pro-brain natriuretic peptide (1-76)
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia : Associations with long-term echocardiographic outcomes. / Lipshultz, Steven E; Miller, Tracie L; Scully, Rebecca E.; Lipsitz, Stuart R.; Rifai, Nader; Silverman, Lewis B.; Colan, Steven D.; Neuberg, Donna S.; Dahlberg, Suzanne E.; Henkel, Jacqueline M.; Asselin, Barbara L.; Athale, Uma H.; Clavell, Luis A.; Laverdier̀e, Caroline; Michon, Bruno; Schorin, Marshall A.; Sallan, Stephen E.

In: Journal of Clinical Oncology, Vol. 30, No. 10, 01.04.2012, p. 1042-1049.

Research output: Contribution to journalArticle

Lipshultz, SE, Miller, TL, Scully, RE, Lipsitz, SR, Rifai, N, Silverman, LB, Colan, SD, Neuberg, DS, Dahlberg, SE, Henkel, JM, Asselin, BL, Athale, UH, Clavell, LA, Laverdier̀e, C, Michon, B, Schorin, MA & Sallan, SE 2012, 'Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: Associations with long-term echocardiographic outcomes', Journal of Clinical Oncology, vol. 30, no. 10, pp. 1042-1049. https://doi.org/10.1200/JCO.2010.30.3404
Lipshultz, Steven E ; Miller, Tracie L ; Scully, Rebecca E. ; Lipsitz, Stuart R. ; Rifai, Nader ; Silverman, Lewis B. ; Colan, Steven D. ; Neuberg, Donna S. ; Dahlberg, Suzanne E. ; Henkel, Jacqueline M. ; Asselin, Barbara L. ; Athale, Uma H. ; Clavell, Luis A. ; Laverdier̀e, Caroline ; Michon, Bruno ; Schorin, Marshall A. ; Sallan, Stephen E. / Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia : Associations with long-term echocardiographic outcomes. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 10. pp. 1042-1049.
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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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T1 - Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia

T2 - Associations with long-term echocardiographic outcomes

AU - Lipshultz, Steven E

AU - Miller, Tracie L

AU - Scully, Rebecca E.

AU - Lipsitz, Stuart R.

AU - Rifai, Nader

AU - Silverman, Lewis B.

AU - Colan, Steven D.

AU - Neuberg, Donna S.

AU - Dahlberg, Suzanne E.

AU - Henkel, Jacqueline M.

AU - Asselin, Barbara L.

AU - Athale, Uma H.

AU - Clavell, Luis A.

AU - Laverdier̀e, Caroline

AU - Michon, Bruno

AU - Schorin, Marshall A.

AU - Sallan, Stephen E.

PY - 2012/4/1

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N2 - 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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