Gender differences in long-term dexrazoxane cardioprotection in doxorubicin-treated children with acute lymphoblastic leukemia

  • Dr Steven Lipshultz, University of Miami Miller School of Medicine, United States
  • Ms Rebecca Scully, University of Miami Miller School of Medicine, United States
  • Dr Stuart Lipsitz, Brigham and Women's Hospital, United States
  • Dr Steven Sallan, Dana-Farber Cancer Institute, United States
  • Dr Lewis Silverman, Dana-Farber Cancer Institute, United States
  • Dr Tracie Miller, University of Miami Miller School of Medicine, United States
  • Dr E John Orav, Brigham and Women's Hospital, United States
  • Dr Steven Colan, Children's Hospital Boston, United States

    • Objective: To evaluate the long-term effect of the cardioprotectant dexrazoxane (DZR) in children undergoing doxorubicin (DOX) chemotherapy for leukemia.

    Methods: We centrally remeasured echocardiograms from childhood leukemia survivors who were randomly assigned to treatment with DOX only (n=66; 30mg/m2/dose for 10 doses) or DOX plus DZR (n=68; 300mg/m2/dose).

    Results: Five years post-treatment, mean LV end systolic dimension (ESD) z-score was significantly larger than predicted for body-surface area for DOX (mean=0.46, P-valuedeviation of mean from normal=0.01) but not for DZR/DOX (0.06, P=0.74); DOX LV fractional shortening (FS; -0.78, P=.001; DZR/DOX=-0.38, P=0.11) and thickness to dimension ratio (-0.96, P<0.001; DZR/DOX=-0.32, P=0.08) were also abnormal. LV end diastolic posterior wall thickness (EDPWT) was reduced in both groups (1.19, P<0.001) than DZR/DOX (-0.74, P<0.001).

    By gender, LVESD z-score was significantly larger than normal for DOX males (mean = 0.48, P=0.04) but not DZR/DOX males (0.19, P=0.41) or females (DOX female=0.38, P=0.22; DZR/DOX female=-0.17, P=0.56). LVFS z-score was significantly different from normal in DOX females (mean=-1.29, P<0.001), but not DZR/DOX females (-0.22, P=0.54) or males (DOX=-0.45, P=0.15; DZR/DOX=-0.52, P=0.09), as was LV thickness to dimension ratio (DOX female=-1.03, P<0.001; DZR/DOX female=0.02, P=0.93). DZR/DOX females were the only group with normal LVEDPWT z-score (mean=-0.43, P=0.07; DOX/female=-1.43, P<0.001; DOX male=-1.05, P<0.001; DZR/DOX male=-0.94, P<0.001).

    Conclusions: Though seen in both genders, primarily females drive the long-term DZR cardioprotective effect. DZR/DOX females exhibit more normal LV dimensions and more appropriate wall thickness for LV dimension, consistent with less LV remodeling.