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Abnormal Cytogenetics at Date of Morphologic Complete Remission Predicts Short Overall and Disease-Free Survival, and Higher Relapse Rate in Adult Acute Myeloid Leukemia: Results From Cancer and Leukemia Group B Study 8461

From the Division of Hematology and Oncology, Department of Internal Medicine, and the Department of Pathology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH; CALGB Statistical Center, Durham; Wake Forest University Medical Center, Winston Salem, NC; University of Alabama at Birmingham, Birmingham, AL; North Shore University Hospital, Manhasset, NY; University of Chicago, Chicago, IL

Address reprint requests to Guido Marcucci, the Comprehensive Cancer Center, The Ohio State University, A433B Starling-Loving Hall, 320 W 10th Ave, Columbus, OH 43210; e-mail: marcucci-1{at}medctr.osu.edu

PURPOSE: As most patients with acute myeloid leukemia (AML) with morphologic complete remission (CR) ultimately relapse, better predictors for outcome are needed. Recently, Cheson et al suggested using cytogenetic remission (CRc) as part of the criteria for CR. To our knowledge, ours is the first relatively large study evaluating the usefulness of CRc attained immediately following induction chemotherapy.

PATIENTS AND METHODS: We included AML patients treated on Cancer and Leukemia Group B front-line studies with cytogenetic samples obtained at diagnosis and at the first day of documented CR following induction. Patients with abnormal cytogenetics at diagnosis, and normal cytogenetics at CR (NCR; n = 103) were compared with those with abnormal cytogenetics both at diagnosis and at CR (ACR; n = 15) for overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR). Cox proportional hazards models determined the prognostic significance of cytogenetics at CR, adjusting for other covariates.

RESULTS: Clinical features were similar for both groups, with the exception of favorable cytogenetics [t(8;21), inv(16)/t(16;16), t(15;17)] at diagnosis, which was more frequent (P = .03) in the NCR group. Median follow-up was 3.1 years (range, 1.0 to 11.4 years). ACR patients had significantly shorter OS (P = .006) and DFS (P = .0001), and higher CIR (P = .0001). In multivariable models, the NCR and ACR groups were predictors for OS (P = .03), DFS (P = .02), and CIR (P = .05). The relative risk of relapse or death was 2.1 times higher for ACR patients than for NCR patients (95% CI, 1.1 to 3.9).

CONCLUSION: Our data suggest that converting to normal karyotype at the time of first CR is an important prognostic indicator and support the use of CRc as a criterion of CR in AML.

Supported in part by National Cancer Institute (Bethesda, MD) grants CA77658, CA101140, CA31946, P30CA16058, and K08-CA90469, and the Coleman Leukemia Research Foundation.

G.M. and K.M. contributed equally to this work.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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