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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-03-0772.
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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4325-4336
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Pretreatment cytogenetic abnormalities are predictive of
induction success, cumulative incidence of relapse, and overall
survival in adult patients with de novo acute myeloid leukemia:
results from Cancer and Leukemia Group B (CALGB
8461)
John C. Byrd,
Krzysztof Mrózek,
Richard
K. Dodge,
Andrew J. Carroll,
Colin G. Edwards,
Diane C. Arthur,
Mark J. Pettenati,
Shivanand R. Patil,
Kathleen W. Rao,
Michael S. Watson,
Prasad R. K. Koduru,
Joseph O. Moore,
Richard M. Stone,
Robert J. Mayer,
Eric J. Feldman,
Frederick R. Davey,
Charles A. Schiffer,
Richard A. Larson, and
Clara D. Bloomfield
From The Ohio State University, Columbus; CALGB
Statistical Center, Durham, NC; University of Alabama at Birmingham;
National Cancer Institute, Bethesda, MD; Wake Forest University Medical
Center, Winston Salem, NC; University of Iowa, Iowa City; University of
North Carolina at Chapel Hill; Washington University, St Louis, MO;
North Shore University Hospital, Manhasset, NY; Duke University Medical
Center, Durham, NC; Dana-Farber Cancer Institute, Boston, MA; Weill
Medical College of Cornell University, New York, NY; SUNY Upstate
Medical University, Syracuse, NY; Karmanos Cancer Institute, Wayne
State University School of Medicine, Detroit, MI; and University of
Chicago, IL.
We analyzed prospectively 1213 adults with de novo acute myeloid
leukemia (AML) to ascertain the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, 5-year cumulative incidence of relapse (CIR), and 5-year overall survival (OS). All
patients received similar induction therapy. Median follow-up for
surviving patients was 8.3 years. Nonprioritized cytogenetics distinguished t(8;21) and inv(16)/t(16;16) as conferring a
significantly better prognosis than normal karyotype. Prognostic impact
of many abnormalities could not be determined independently because of their association with complex karyotype. Neither complex karyotype nor
secondary aberrations affected outcome of patients with t(8;21), inv(16)/t(16;16), or t(9;11). Among other patients, those with complex
karyotypes had significantly worse outcomes than cytogenetically normal
patients. Based on outcome for specific cytogenetic abnormalities and
karyotype complexity, patients were divided into 3 risk groups: favorable (CR 88%, CIR 54%, OS 55%), intermediate (CR 67%, CIR 67%, OS 24%), and adverse (CR 32%, CIR 92%, OS 5%). Multivariate analyses confirmed the major contribution of cytogenetics to the probability of attaining CR, CIR, and OS. For the adverse-risk group,
the probability of achieving CR was 4.0 and 11.9 times lower, the
probability of relapse 3.0 and 4.4 times higher, and the risk of death
2.1 and 4.3 times higher than those for the intermediate and favorable
groups, respectively. We conclude that although the prognostic impact
of many recurring abnormalities has not been ascertained independently
of complex karyotype, cytogenetics is among the most useful factors
predicting attainment of CR, CIR, and long-term survival in adult AML.

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