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Previous Volume 351:145-153 July 8, 2004 Number 2 Next

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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.

Source Information

From the Department of Pediatrics, University of Miami School of Medicine, Holtz Children's Hospital of the University of Miami/Jackson Memorial Medical Center and the Sylvester Comprehensive Cancer Center, Miami (S.E.L.); Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, N.Y. (S.E.L., B.L.A.); the Departments of Laboratory Medicine and Pathology, Children's Hospital, Boston (N.R.); the Departments of Pediatric Oncology (V.M.D., L.B.S., S.E.S.) and Biostatistical Science (D.E.L., S.R.L., R.D.G.), Dana–Farber Cancer Institute, Boston; the Division of Hematology/Oncology (L.B.S., S.E.S.) and the Department of Cardiology (S.D.C.), Children's Hospital, Boston; the Department of Pediatrics, Harvard Medical School, Boston (L.B.S., S.D.C., S.E.S.); the Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston (S.R.L.); the Department of Pediatrics, McMaster University, Hamilton, Ont., Canada (R.D.B.); San Jorge Children's Hospital, Santurce, Puerto Rico (L.A.C.); Maine Children's Cancer Program, Barbara Bush Children's Hospital at Maine Medical Center, Portland (C.A.H.); St. Justine Hospital, Montreal (A.M.); Le Centre Hospitalier Universitaire de Québec, Quebec Canada (Y.S.); and the Department of Pediatrics, Ochsner Clinic Foundation and Tulane University School of Medicine, New Orleans (M.A.S.).

Address reprint requests to Dr. Lipshultz at the Department of Pediatrics (D820), University of Miami School of Medicine, P.O. Box 016820, Miami, FL 33101, or at slipshultz{at}med.miami.edu.

Full Text of this Article

Related Letters:

Doxorubicin-Induced Myocardial Injury
Fujisaki G., Inokuchi C., Murashige N., Lipshultz S. E., Silverman L. B., Sallan S. E.
Extract | Full Text | PDF  
N Engl J Med 2004; 351:1908-1909, Oct 28, 2004. Correspondence

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