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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.

© 2002 by The American Society of Hematology.
 

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