Alix E. Seif and Dana M. Walker contributed equally to this work.
Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric oncology patients
Article first published online: 26 MAR 2014
© 2014 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
How to Cite
Seif, A. E., Walker, D. M., Li, Y., Huang, Y.-S. V., Kavcic, M., Torp, K., Bagatell, R., Fisher, B. T. and Aplenc, R. (2014), Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric oncology patients. Pediatr. Blood Cancer. doi: 10.1002/pbc.25043
Conflict of interest: Author Brian T. Fisher receives research support from Pfizer Pharmaceuticals. All other authors declare that they have no conflicts of interest.
- Article first published online: 26 MAR 2014
- Manuscript Accepted: 28 FEB 2014
- Manuscript Received: 2 DEC 2013
- National Cancer Institute, National Institutes of Health. Grant Number: 1 R01 CA3881-01
- The Alex's Lemonade Stand Foundation, Center for Childhood Cancer Research Seed Grant
- American Cancer Society, Mentored Research Scientist Grant in Applied and Clinical Research. Grant Number: MRSG-12-215-01-LIB
- cardiotoxicity after cancer therapy;
- secondary malignancy;
Dexrazoxane may reduce anthracycline-associated cardiotoxicity in pediatric cancer patients. However, concerns of secondary acute myeloid leukemia (AML) have led to restrictions on pediatric dexrazoxane use in Europe. Published data about dexrazoxane-associated secondary AML are limited and conflicting. We sought to estimate the secondary AML risk in children receiving dexrazoxane after anthracycline exposure.
A retrospective cohort of children with newly identified malignancies (excluding AML) receiving anthracyclines between January 1, 1999 and March 31, 2011 was established using the Pediatric Health Information System (PHIS). Patients were followed for all subsequent admissions to identify dexrazoxane exposures and secondary AML, defined by AML ICD-9 codes and AML induction chemotherapy. Logistic regression was used to model the association of dexrazoxane and secondary AML risk. A propensity score was used to adjust for measurable confounding.
Of 15,532 patients in the cohort exposed to anthracyclines, 1,406 received dexrazoxane. The secondary AML rate was 0.21% (3 of 1,046) in dexrazoxane-exposed and 0.55% (77 of 14,126) in unexposed patients. In a propensity score-adjusted multivariate analysis, dexrazoxane exposure was not associated with an increased risk of secondary AML, OR = 0.38, 95% CI 0.11–1.26.
Dexrazoxane was not associated with an increased risk of secondary AML in a large cohort of pediatric cancer patients receiving anthracyclines in US hospitals. While these data support dexrazoxane's safety in the general pediatric oncology population, additional studies are needed to confirm these findings and to quantify dexrazoxane's long-term cardioprotective effects. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.