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Author Notes:

April D. Sorrell, MD, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000; Fax: (626) 256-8723; asorrell@coh.org.

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.

We gratefully thank the members of each participating Children’s Oncology Group institution and the families and children who participated in this trial.

The authors made no disclosures.

Subject:

Research Funding:

This work was supported by the National Institutes of Health (U10 CA98543 and U10 CA98413).

Dr. Arceci was supported by an endowed King Fahd Professorship.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • myelodysplastic syndrome
  • myeloid leukemia
  • Down syndrome
  • Children's Oncology Group Trial A2971
  • TRANSIENT MYELOPROLIFERATIVE DISORDER
  • HIGH CURE RATE
  • MYELODYSPLASTIC SYNDROME
  • GATA1 MUTATIONS
  • CANCER GROUP
  • AML
  • THERAPY
  • CLASSIFICATION
  • LEUKEMOGENESIS
  • CYTARABINE

Favorable Survival Maintained in Children Who Have Myeloid Leukemia Associated With Down Syndrome Using Reduced-Dose Chemotherapy on Children’s Oncology Group Trial A2971

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Journal Title:

Cancer

Volume:

Volume 118, Number 19

Publisher:

, Pages 4806-4814

Type of Work:

Article | Post-print: After Peer Review

Abstract:

BACKGROUND: 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). METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Copyright information:

© 2012 American Cancer Society.

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