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

Maureen M. O'Brien, Jeffrey W. Taub, Myron N. Chang, Gita V. Massey, Kimo C. Stine, Susana C. Raimondi, David Becton, Yaddanapudi Ravindranath, Gary V. Dahl

From the Division of Pediatric Hematology/Oncology, Lucile Packard Children's Hospital, Stanford, CA; Children's Hospital of Michigan, Detroit, MI; Medical College of Virginia, Richmond, VA; Arkansas Children's Hospital, Little Rock, AR; St Jude Children's Research Hospital, Memphis, TN; and Children's Oncology Group, Arcadia, CA

Corresponding author: Gary V. Dahl, MD, Lucile Packard Children's Hospital at Stanford, Division of Pediatric Hematology/Oncology, 1000 Welch Rd, Suite 300, Palo Alto, CA 94304; e-mail: gary.dahl{at}stanford.edu

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.

Supported in part by the National Institutes of Health Grant No. RO1 CA90916 (G.V.D.). A complete listing of grant support for research conducted by the Children's Cancer Group (CCG) and by the Pediatric Oncology Group (POG) before initiation of the Children's Oncology Group (COG) grant in 2003 is available online at http://www.childrensoncologygroup.org/admin/grantinfo.htm.

Presented in part at the 48th Annual Meeting and Exposition of the American Society of Hematology, December 9-12, 2006, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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