title: Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric oncology patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Alix E
authors.initials: AE
authors.lastname: Seif
authors.forename: Dana M
authors.initials: DM
authors.lastname: Walker
authors.forename: Yimei
authors.initials: Y
authors.lastname: Li
authors.forename: Yuan-Shung V
authors.initials: YS
authors.lastname: Huang
authors.forename: Marko
authors.initials: M
authors.lastname: Kavcic
authors.forename: Kari
authors.initials: K
authors.lastname: Torp
authors.forename: Rochelle
authors.initials: R
authors.lastname: Bagatell
authors.forename: Brian T
authors.initials: BT
authors.lastname: Fisher
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D054715:Cardiotoxins / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D064730:Dexrazoxane / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D018943:Anthracyclines; D002316:Cardiotonic Agents; D054715:Cardiotoxins; D064730:Dexrazoxane
keywords: cardiotoxicity after cancer therapy; dexrazoxane; epidemiology; secondary malignancy