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

• Authors: April D. Sorrell, City Hope National Medical Center; Todd A. Alonzo, University of Southern California; Joanne M. Hilden, Peyton Manning Children’s Hospital at St. Vincent; Robert B. Gerbing, Children’s Oncology Group; Thomas W. Loew, University of Iowa; Lois Hathaway, Children's Hospital of Pittsburgh; Dorothy Barnard, IWK Health Centre; Jeffrey W. Taub, Children's Hospital of Michigan; Yaddanapudi Ravindranath, Children's Hospital of Michigan; Franklin O. Smith, Cincinnati Children’s Hospital Medical Center; Robert J. Arceci, Johns Hopkins University; William G Woods, Emory University; Alan S. Gamis, Children’s Mercy Hospital and Clinics
• Journal Title: Cancer
• Volume: Volume 118, Number 19
• Publisher: Wiley: 12 months | 2012-10-01, Pages 4806-4814
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/cncr.27484
• Subjects: Health Sciences, Medicine and Surgery
• 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

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.