The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia

Steven E Lipshultz, Nader Rifai, Virginia M. Dalton, Donna E. Levy, Lewis B. Silverman, Stuart R. Lipsitz, Steven D. Colan, Barbara L. Asselin, Ronald D. Barr, Luis A. Clavell, Craig A. Hurwitz, Albert Moghrabi, Yvan Samson, Marshall A. Schorin, Richard D. Gelber, Stephen E. Sallan

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Abstract

BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter) - the primary end point - or extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

Original languageEnglish
Pages (from-to)145-153
Number of pages9
JournalNew England Journal of Medicine
Volume351
Issue number2
DOIs
StatePublished - Jul 8 2004

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Dexrazoxane
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Doxorubicin
Troponin T
Wounds and Injuries
Disease-Free Survival
Free Radical Scavengers
Body Surface Area
Serum
Cardiac Myocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lipshultz, S. E., Rifai, N., Dalton, V. M., Levy, D. E., Silverman, L. B., Lipsitz, S. R., ... Sallan, S. E. (2004). The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. New England Journal of Medicine, 351(2), 145-153. https://doi.org/10.1056/NEJMoa035153

The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. / Lipshultz, Steven E; Rifai, Nader; Dalton, Virginia M.; Levy, Donna E.; Silverman, Lewis B.; Lipsitz, Stuart R.; Colan, Steven D.; Asselin, Barbara L.; Barr, Ronald D.; Clavell, Luis A.; Hurwitz, Craig A.; Moghrabi, Albert; Samson, Yvan; Schorin, Marshall A.; Gelber, Richard D.; Sallan, Stephen E.

In: New England Journal of Medicine, Vol. 351, No. 2, 08.07.2004, p. 145-153.

Research output: Contribution to journalArticle

Lipshultz, SE, Rifai, N, Dalton, VM, Levy, DE, Silverman, LB, Lipsitz, SR, Colan, SD, Asselin, BL, Barr, RD, Clavell, LA, Hurwitz, CA, Moghrabi, A, Samson, Y, Schorin, MA, Gelber, RD & Sallan, SE 2004, 'The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia', New England Journal of Medicine, vol. 351, no. 2, pp. 145-153. https://doi.org/10.1056/NEJMoa035153
Lipshultz, Steven E ; Rifai, Nader ; Dalton, Virginia M. ; Levy, Donna E. ; Silverman, Lewis B. ; Lipsitz, Stuart R. ; Colan, Steven D. ; Asselin, Barbara L. ; Barr, Ronald D. ; Clavell, Luis A. ; Hurwitz, Craig A. ; Moghrabi, Albert ; Samson, Yvan ; Schorin, Marshall A. ; Gelber, Richard D. ; Sallan, Stephen E. / The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. In: New England Journal of Medicine. 2004 ; Vol. 351, No. 2. pp. 145-153.
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abstract = "BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter) - the primary end point - or extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.",
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AU - Levy, Donna E.

AU - Silverman, Lewis B.

AU - Lipsitz, Stuart R.

AU - Colan, Steven D.

AU - Asselin, Barbara L.

AU - Barr, Ronald D.

AU - Clavell, Luis A.

AU - Hurwitz, Craig A.

AU - Moghrabi, Albert

AU - Samson, Yvan

AU - Schorin, Marshall A.

AU - Gelber, Richard D.

AU - Sallan, Stephen E.

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N2 - BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter) - the primary end point - or extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

AB - BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter) - the primary end point - or extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

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