Originally published as JCO Early Release 10.1200/JCO.2003.08.060 on July 28 2003

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Increased Age at Diagnosis Has a Significantly Negative Effect on Outcome in Children With Down Syndrome and Acute Myeloid Leukemia: A Report From the Children’s Cancer Group Study 2891

From the Children’s Mercy Hospital, Kansas City, MO; Children’s Healthcare of Atlanta at Egleston, Atlanta, GA; Children’s Oncology Group, Arcadia, and University of Southern California Keck School of Medicine, Los Angeles, CA; Children’s Hospital of Philadelphia, Philadelphia, PA; IWK Health Centre, Halifax, Nova Scotia, Canada; University of North Carolina at Chapel Hill, Chapel Hill, NC; and Children’s Hospital Medical Center, Cincinnati, OH.

Address reprint requests to Alan S. Gamis, MD, MPH, Section of Hematology/Oncology/Blood and Marrow Transplantation, Children’s Mercy Hospital and Clinics, 2401 Gillham Rd, Kansas City, MO 64108; e-mail: agamis{at}cmh.edu.

Purpose: To determine the outcome of children with Down syndrome (DS) and acute myeloid leukemia (AML) receiving standard timing chemotherapy without bone marrow transplantation (BMT), with determination of prognostic factors.

Patients and Methods: Children with DS and newly diagnosed AML or myelodysplasia were prospectively enrolled on Children’s Cancer Group study 2891 (N = 161) and treated uniformly with four standard timing induction courses of dexamethasone, cytarabine arabinoside, 6-thioguanine, etoposide, daunorubicin (DCTER) followed by intensively timed high-dose cytarabine.

Results: Children with DS were significantly younger at diagnosis than those without (median age, 1.8 v 7.5 years, respectively; P < .001), with more megakaryocytic leukemia (70% v 6%; P < .001). Higher complete remission rates (91%) were achieved in children with DS than among those without DS (75%; P < .001). Equivalent grade 3 to 4 toxicity (29% v 30%; P = .84) was seen, though children with DS had greater pulmonary toxicity (P < .01) during induction and mucositis during intensification (P = .12). Children with DS had significantly better 8-year event-free survival (EFS; 77% v 21% standard and 40% intensive induction; P < .0001). Multivariate analysis in children with DS revealed that only age at diagnosis of 2 years or older was a risk factor for greater relapse risk (odds ratio, 4.9; P = .006) and worse survival. Children between ages 0 to 2 years (n = 94) had a 6-year EFS of 86%; those from 2 to 4 years (n = 58), 70%; and those older than 4 years (n = 9), 28%. Remission failures were the primary reason for worse 6-year EFSs (1% in those 0 to 2 years v 14% if >2 years; P = .002).

Conclusion: Outcome for children with DS and AML is excellent with standard induction therapy, but declines with increasing age.

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