23 de enero de 2012

Cardiomyopathy in Children With Down Syndrome Treated for Acute Myeloid Leukemia: A Report From the Children's Oncology Group Study POG 9421


American Society of Clinical Oncology

Maureen M. O'Brien, Jeffrey W. Taub, Myron N. Chang, Gita V. Massey, Kimo C. Stine,

Susana C. Raimondi, David Becton, Yaddanapudi Ravindranath and Gary V. Dahl
Abstract
Purpose To determine the outcomes, with particular attention to toxicity, of children with Down syndrome (DS) and acute myeloid leukemia (AML) treated on Pediatric Oncology Group (POG) protocol 9421.
Patients and Methods Children with DS and newly diagnosed AML (n = 57) were prospectively enrolled onto the standard-therapy arm of POG 9421 and were administered five cycles of chemotherapy, which included daunorubicin 135 mg/m2 and mitoxantrone 80 mg/m2. Outcomes and toxicity were evaluated prospectively and were compared with the non-DS–AML cohort (n = 565). A retrospective chart review was performed to identify adverse cardiac events.
Results In the DS-AML group, 54 patients (94.7%) entered remission. One experienced induction failure and two died. Of the 54 who entered remission, three relapsed and six died as a result of other causes. The remission induction rate was similar in the non-DS–French-American-British (FAB) M7 (91.7%) and non-DS–non-M7 (89.3%) groups. The 5-year overall survival was significantly better in the DS-AML group (78.6%) than in the non-DS–M7 (36.3%) or the non-DS–non-M7 (51.8%) groups (P < .001). No age-related difference in 5-year, event-free survival was seen between patients younger than 2 years (75.8%) and those aged 2 to 4 years (78.3%). Symptomatic cardiomyopathy developed in 10 patients (17.5%) with DS-AML during or soon after completion of treatment; three died as a result of congestive heart failure.
Conclusion The POG 9421 treatment regimen was highly effective in both remission induction and disease-free survival for patients with DS-AML. However, there was a high incidence of cardiomyopathy, which supports current strategies for dose reduction of anthracyclines in this patient population.