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

April D. Sorrell, Todd A. Alonzo, Joanne M. Hilden, Robert B. Gerbing, Thomas W. Loew, Lois Hathaway, Dorothy Barnard, Jeffrey W. Taub, Yaddanapudi Ravindranath, Franklin O. Smith, Robert J. Arceci, William G. Woods, Alan S. Gamis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4806-4814
Number of pages9
JournalCancer
Volume118
Issue number19
DOIs
StatePublished - Oct 1 2012

Keywords

  • Children's Oncology Group Trial A2971
  • Down syndrome
  • myelodysplastic syndrome
  • myeloid leukemia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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., & 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: A report from the Children's Oncology Group. Cancer, 118(19), 4806-4814. https://doi.org/10.1002/cncr.27484