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Prognostic Impact of Trisomies of Chromosomes 10, 17, and 5 Among Children With Acute Lymphoblastic Leukemia and High Hyperdiploidy (> 50 Chromosomes)

From the Department of Genetics, Hughes Institute, and Children’s Cancer Group Acute Lymphoblastic Leukemia Biology Reference Laboratory, St. Paul; Department of Hematology-Oncology, Children’s Health Care, Minneapolis, MN; Department of Preventive Medicine, University of Southern California, and Department of Pediatric Hematology-Oncology, Children’s Hospital, Los Angeles; Group Operations Center, Children’s Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Michigan, Ann Arbor, MI; Department of Pediatric Hematology-Oncology, University of Chicago, Chicago, IL; Division of Oncology, Children’s Hospital of Philadelphia, PA; Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY; and Children’s National Medical Center and George Washington University School of Medicine, Washington, DC.

Address reprint requests to Nyla A. Heerema, PhD, c/o The Children’s Cancer Group, Attn Lucia Noll, PO Box 60012, Arcadia, CA 91066-6012; nheerema{at}ih.org

PURPOSE: Children with acute lymphoblastic leukemia (ALL) and high hyperdiploidy (> 50 chromosomes) have improved outcome compared with other ALL patients. We sought to identify cytogenetic features that would predict differences in outcome within this low-risk subset of ALL patients.

MATERIALS AND METHODS: High-hyperdiploid ALL patients (N = 480) were enrolled between 1988 and 1995 on Children’s Cancer Group (CCG) trials. Karyotypes were determined by conventional banding. Treatment outcome was analyzed by life-table methods.

RESULTS: Patients with 54 to 58 chromosomes had better outcome than patients with 51 to 53 or 59 to 68 chromosomes (P = .0002). Patients with a trisomy of chromosome 10 (P < .0001), chromosome 17 (P = .0002), or chromosome 18 (P = .004) had significantly improved outcome compared with their counterparts who lacked the given trisomy. Patients with a trisomy of chromosome 5 had worse outcome than patients lacking this trisomy (P = .02). Patients with trisomies of both chromosomes 10 and 17 had better outcome than those with a trisomy of chromosome 10 (P = .09), a trisomy of chromosome 17 (P = .01), or neither trisomy (P < .0001). Multivariate analysis indicated that trisomy of chromosome 10 (P = .001) was the most significant prognostic factor for high-hyperdiploid patients, yet trisomy of chromosome 17 (P = .02) or chromosome 5 (P = .01) and modal chromosome number (P = .02) also had significant multivariate effects.

CONCLUSION: Trisomy of chromosomes 10 and 17 as well as modal chromosome number 54 to 58 identify subgroups of patients with high-hyperdiploid ALL who have a better outcome than high-hyperdiploid patients who lack these cytogenetic features. Trisomy of chromosome 5 confers poorer outcome among high-hyperdiploid patients.

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