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Prognostic Factors and Outcome of Core Binding Factor Acute Myeloid Leukemia Patients With t(8;21) Differ From Those of Patients With inv(16): A Cancer and Leukemia Group B Study

From the Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH; The CALGB Statistical Center and Duke University Medical Center, Durham, NC; North Shore University Hospital, Manhasset, NY; Dana-Farber Cancer Institute, Boston, MA; Wake Forest University School of Medicine, Winston-Salem, NC; University of Chicago, Chicago, IL; Wayne State University School of Medicine, Detroit, MI; and University of Alabama at Birmingham, Birmingham, AL

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

PURPOSE: Because both t(8;21) and inv(16) disrupt core binding factor (CBF) in acute myeloid leukemia (AML) and confer relatively favorable prognoses, these cytogenetic groups are often treated similarly. Recent studies, however, have shown different gene profiling for the two groups, underscoring potential biologic differences. Therefore, we sought to determine whether these two cytogenetic groups should also be considered separate entities from a clinical standpoint.

PATIENTS AND METHODS: We analyzed 144 consecutive adults with t(8;21) and 168 with inv(16) treated on Cancer and Leukemia Group B front-line studies. We compared pretreatment features, probability of achieving complete remission (CR), overall survival (OS) and cumulative incidence of relapse (CIR) between the two groups.

RESULTS: With a median follow-up of 6.4 years, for CBF AML as a whole, the CR rate was 88%, 5-year OS was 50% and CIR was 53%. After adjusting for covariates, patients with t(8;21) had shorter OS (hazard ratio [HR] = 1.5; P = .045) and survival after first relapse (HR = 1.7; P = .009) than patients with inv(16). Unexpectedly, race was an important predictor for t(8;21) AML, in that nonwhites failed induction more often (odds ratio = 5.7; P = .006) and had shorter OS than whites when certain secondary cytogenetic abnormalities were present. In patients with t(8;21) younger than 60 years, type of induction also correlated with relapse risk. For inv(16) AML, secondary cytogenetic abnormalities (especially +22) and male sex predicted better outcome.

CONCLUSION: When the prognostic impact of race, secondary cytogenetic abnormalities, sex, and response to salvage treatment is considered, t(8;21) and inv(16) AMLs seem to be distinct clinical entities and should be stratified and reported separately.

Supported by National Cancer Institute grants No. CA77658, CA101140, CA31946, P30-CA16058, and K08-CA90469, and by The Coleman Leukemia Research Foundation.

Both 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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