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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4036-4045
Hypodiploidy With Less Than 45 Chromosomes Confers Adverse Risk in
Childhood Acute Lymphoblastic Leukemia: A Report From the
Children's Cancer Group
Nyla A. Heerema,
James B. Nachman,
Harland N. Sather,
Martha G. Sensel,
Mei K. Lee,
Raymond Hutchinson,
Beverly J. Lange,
Peter G. Steinherz,
Bruce Bostrom,
Paul S. Gaynon, and
Fatih Uckun
From the Department of Genetics, Hughes Institute, St Paul, MN; the
Department of Pediatric Hematology-Oncology, University of Chicago,
Chicago, IL; the Department of Preventive Medicine, University of
Southern California, Los Angeles, CA; the Group Operations Center,
Children's Cancer Group, Arcadia, CA; the Department of Pediatric
Hematology-Oncology, University of Michigan, Ann Arbor, MI; the
Division of Oncology, Children's Hospital of Philadelphia, PA; the
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New
York, NY; the Department of Hematology-Oncology, Children's Hospitals
and Clinics, Minneapolis, MN; the Department of Pediatric
Hematology-Oncology, Children's Hospital, Los Angeles, CA; and the
Children's Cancer Group ALL Biology Reference Laboratory, Hughes
Institute, St Paul, MN. Contributing CCG cytogeneticists are given in
the Acknowledgment.
We have determined the prognostic significance of hypodiploidy
(<46 chromosomes) in a large cohort of children with acute lymphoblastic leukemia (ALL) treated by the Children's
Cancer Group. Among 1,880 patients, 110 (5.8%) had hypodiploid
karyotypes: 87 had 45 chromosomes, 15 had 33 to 44 chromosomes, none
had 29 to 32 chromosomes, and 8 had 24 to 28 chromosomes
(near-haploidy). Six-year event-free survival (EFS) estimates for
patients with 45 chromosomes, 33 to 44 chromosomes, or 24 to 28 chromosomes were 65% (standard deviation [SD], 8%), 40% (SD,
18%), and 25% (SD, 22%), respectively (log rank, P = .002;
test for trend, P = .0009). The combined hypodiploid group
had worse outcome than nonhypodiploid patients, with 6-year EFS of 58%
(SD, 7%) and 76% (SD, 2%), respectively (P < .0001). EFS
for the subgroup with 45 chromosomes was similar to that of patients
with pseudodiploidy (P = .43) or 47 to 50 chromosomes
(P = .76). None of the patients with 24 to 28 chromosomes had
a t(4;11), a t(9;22), or a t(1;19), and most received highly intensive
therapy. The adverse risk associated with 33 to 44 and 24 to 28 chromosomes remained significant in multivariate analyses adjusted for
important risk factors including age, white blood cell count, and
Philadelphia chromosome status. Thus, hypodiploidy with less than 45 chromosomes, particularly 24 to 28 chromosomes, is a significant
adverse risk factor despite treatment with contemporary intensive therapies.
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