Abstract 6073: Dexrazoxane Cardioprotection in Doxorubicin-Treated Children with Acute Lymphoblastic Leukemia: Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocol 95–01 Randomized Controlled Trial

Abstract

Background: Doxorubicin (DOX) chemotherapy injures myocardial cells, leading to progressive cardiac dysfunction. Dexrazoxane (DZR), a free-radical scavenger, reduced troponin T (cTnT) elevation during therapy in children with acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute (DFCI) Protocol 95– 01. The long-term cardiac benefits of DZR are not yet known. Methods: We centrally remeasured echocardiograms from childhood ALL survivors who were randomly assigned to DOX (n =64; 30 mg/m 2 /dose for 10 doses) with or without DZR (n =58; 300 mg/m 2 /dose) during DFCI Protocol 95– 01. Results: Demographics and follow-up were similar in both arms (median f/u years: DOX 4.0 vs. DZR/DOX 3.7). Mean left ventricular (LV) end-systolic dimension was significantly abnormal for DOX vs. DZR/DOX at 3 years (mean Z-score: DOX 0.637 vs. DZR/DOX −0.0005, P=0.0164) and progressed at 3.5 years (0.800 vs. −0.006, P=0.0028) and 4 years (1.01 vs. 0.005, P=0.0013). DOX-group mean LV end-diastolic (ED) dimension was significantly dilated at 3.5 years (mean Z-score: DOX 0.223 vs. DZR/DOX −0.424, P=0.022) and 4 years (0.428 vs. −0.456, P=0.004). With 3.5 years follow-up, a number of non-significant trends showed DZR/DOX echo measures to be more normal: LV fractional shortening Z-score (DOX −2.092 vs. DZR/DOX −1.00); LV mass Z-score (−0.672 vs. −0.537); LVED posterior wall thickness Z-score (LVEDPWTz; −0.596 vs. −0.395). For DZR/DOX-patients, cTnT elevation (defined as >0.01 ng/ml) during DOX treatment correlated with thinner LVED posterior wall 3.5 years post treatment (mean LVEDPWTz: cTnT− =−0.011 vs. cTnT+= −1.200, P=0.0352). Conclusions: DZR is protective against late DOX cardiotoxicity with smaller LV dimensions, consistent with less LV remodeling. LV function, thickness, and mass trended to more normal among children who received DZR and all parameters trended toward a greater DZR effect over time. Further, cTnT elevation during therapy predicted late LV wall thinning. Table 1: Post-treatment Mean Differences in Dimension Z-Scores