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Favorable survival maintained in children who have myeloid leukemia associated with Down syndrome using reduced-dose chemotherapy on Children's Oncology Group trial A2971†‡
A report from the Children's Oncology Group
Article first published online: 5 MAR 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 19, pages 4806–4814, 1 October 2012
How to Cite
Sorrell, A. D., Alonzo, T. A., Hilden, J. M., Gerbing, R. B., Loew, T. W., Hathaway, L., Barnard, D., Taub, J. W., Ravindranath, Y., Smith, F. O., Arceci, R. J., Woods, W. G. and Gamis, A. S. (2012), Favorable survival maintained in children who have myeloid leukemia associated with Down syndrome using reduced-dose chemotherapy on Children's Oncology Group trial A2971. Cancer, 118: 4806–4814. doi: 10.1002/cncr.27484
We gratefully thank the members of each participating Children's Oncology Group institution and the families and children who participated in this trial.
A.D.S. performed research, participated in study design and data analysis, and wrote the article; A.S.G. designed the study, performed research and data analysis, and helped write the article; T.A.A. and R.B.G. participated in study design and data analysis and helped write the article; J.M.H., F.O.S., W.G.W., and R.A. contributed to study design, performed research and data analysis, and critically reviewed the article; T.W.L., L.H., D.B., J.T., and Y.R. performed research and reviewed the article.
- Issue published online: 19 SEP 2012
- Article first published online: 5 MAR 2012
- Manuscript Accepted: 4 JAN 2012
- Manuscript Revised: 8 DEC 2011
- Manuscript Received: 20 OCT 2011
- myelodysplastic syndrome;
- myeloid leukemia;
- Down syndrome;
- Children's Oncology Group Trial A2971
Children who are treated for myeloid leukemia associated with Down syndrome (DS) experience superior survival compared with children who have myeloid leukemia without DS. To maintain excellent outcomes while avoiding toxicity, the Children's Oncology Group (COG) conducted the phase 3 trial COG A2971, the first trial solely designed to provide uniform treatment of myeloid leukemia in North American children with DS. A2971 eliminated 2 induction drugs and 3 months of maintenance therapy from the standard-timing regimen of dexamethasone, cytarabine, 6-thioguanine, etoposide, and rubidomycin/daunomycin (DCTER) used in the previous study (Children's Cancer Group [CCG] 2891).
COG A2971 was a multi-institutional, nonrandomized, clinical trial that enrolled 132 patients who had DS with either acute myeloid leukemia (n = 91) or myelodysplastic syndrome (n = 41).
The median follow-up was 4.8 years (range, 0.8-8.6 years), the median age at diagnosis was 1.7 years (range, 0.3-13.6 years), and the median white blood cell count was 6200/μL (range, 900-164,900/μL). The remission rate (92.7% ± 6%) was similar to that reported in the CCG 2891 study (91.3% ± 5%; P = .679). The 5-year event free survival (EFS) rate was 79% ± 7% (vs 77% ± 7% in CCG 2891; P = .589), the disease-free survival (DFS) rate was 89% ± 6% (vs 85% ± 6% in CCG 2891; P = .337), and the overall survival rate was 84% ± 6% (vs 79% ± 7% in CCG 2891; P = .302). Induction day-14 bone marrow response trended toward a more favorable outcome (EFS: P = .12). Age >4 years was an adverse risk factor (5-year EFS rate: 33% ± 38% for children aged >4 years [median, 8.5 years; n = 6] vs 81% ± 7% for children ages 0-4 years [median, 1.7 years; n = 126]; P = .001).
The COG A2971 trial reduced the chemotherapy dose and maintained survival to that achieved by the CCG 2891 trial in children who had myeloid leukemia associated with DS. Cancer 2012. © 2012 American Cancer Society.