Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term Cardiac Outcomes Journal Articles uri icon

  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All


  • BACKGROUND AND OBJECTIVES: Doxorubicin, effective against many malignancies, is limited by cardiotoxicity. Continuous-infusion doxorubicin, compared with bolus-infusion, reduces early cardiotoxicity in adults. Its effectiveness in reducing late cardiotoxicity in children remains uncertain. We determined continuous-infusion doxorubicin cardioprotective efficacy in long-term survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: The Dana-Farber Cancer Institute ALL Consortium Protocol 91-01 enrolled pediatric patients between 1991 and 1995. Newly diagnosed high-risk patients were randomly assigned to receive a total of 360 mg/m2 of doxorubicin in 30 mg/m2 doses every 3 weeks, by either continuous (over 48 hours) or bolus-infusion (within 15 minutes). Echocardiograms at baseline, during, and after doxorubicin therapy were blindly remeasured centrally. Primary outcomes were late left ventricular (LV) structure and function. RESULTS: A total of 102 children were randomized to each treatment group. We analyzed 484 serial echocardiograms from 92 patients (n = 49 continuous; n = 43 bolus) with ≥1 echocardiogram ≥3 years after assignment. Both groups had similar demographics and normal baseline LV characteristics. Cardiac follow-up after randomization (median, 8 years) showed changes from baseline within the randomized groups (depressed systolic function, systolic dilation, reduced wall thickness, and reduced mass) at 3, 6, and 8 years; there were no statistically significant differences between randomized groups. Ten-year ALL event-free survival rates did not differ between the 2 groups (continuous-infusion, 83% versus bolus-infusion, 78%; P = .24). CONCLUSIONS: In survivors of childhood high-risk ALL, continuous-infusion doxorubicin, compared with bolus-infusion, provided no long-term cardioprotection or improvement in ALL event-free survival, hence provided no benefit over bolus-infusion.


  • Lipshultz, Steven E
  • Miller, Tracie L
  • Lipsitz, Stuart R
  • Neuberg, Donna S
  • Dahlberg, Suzanne E
  • Colan, Steven D
  • Silverman, Lewis B
  • Henkel, Jacqueline M
  • Franco, Vivian I
  • Cushman, Laura L
  • Asselin, Barbara L
  • Clavell, Luis A
  • Athale, Uma
  • Michon, Bruno
  • Laverdière, Caroline
  • Schorin, Marshall A
  • Larsen, Eric
  • Usmani, Naheed
  • Sallan, Stephen E

publication date

  • December 1, 2012

has subject area