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Repetitive Cycles of High-Dose Cytarabine Benefit Patients With Acute Myeloid Leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): Results from CALGB 8461

From The Ohio State University, Columbus, OH; Cancer and Leukemia Group B Statistical Center; Duke University Medical Center, Durham; Wake Forest University Medical Center, Winston Salem, NC; University of Alabama at Birmingham, Birmingham, AL; National Cancer Institute, Bethesda; University of Maryland Cancer Center, Baltimore, MD; North Shore University Hospital, Manhasset; State University of New York Upstate Medical University, Syracuse, NY; Dana-Farber Cancer Institute, Boston, MA; and University of Chicago, Chicago, IL

Address reprint requests to John C. Byrd, MD, Division of Hematology and Oncology and the Comprehensive Cancer Center, The Ohio State University, B302A Starling Loving Hall, 320 W 10th Ave, Columbus, OH 43210-1240; e-mail: byrd-3{at}medctr.osu.edu

PURPOSE: To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and inv(16)(p13q22) or t(16;16)(p13;q22).

PATIENTS AND METHODS: We examined the cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) for 48 adults younger than 60 years with inv(16)/t(16;16) who had attained a complete remission on one of four consecutive clinical trials and were assigned to receive HDAC consolidation therapy. Twenty-eight patients were assigned to either three or four courses of HDAC, and 20 patients were assigned to one course of HDAC followed by alternative intensive consolidation therapy.

RESULTS: Pretreatment features were similar for the two groups. The CIR was significantly decreased in patients assigned to receive three to four cycles of HDAC compared with patients assigned to one course (P = .03; 5-year CIR, 43% v 70%, respectively). The difference in RFS also approached statistical significance (P = .06). In a multivariable analysis that adjusted for potential confounding covariates, only treatment assignment (three to four cycles of HDAC) predicted for superior RFS (P = .02). The OS of both groups was similar (P = .93; 5-year OS, 75% for the three to four cycles of HDAC group v 70% for the one cycle of HDAC group), reflecting a high success rate with stem-cell transplantation salvage treatment administered among patients in both treatment groups.

CONCLUSION: We conclude that, in AML patients with inv(16)/t(16;16), repetitive HDAC therapy decreases the likelihood of relapse compared with consolidation regimens including less HDAC.

Supported by National Cancer Institute grants CA101140, CA31946, CA16058, and CA77658, the Kimmel Cancer Research Foundation, the Leukemia and Lymphoma Society of America, the D. Warren Brown Foundation, and the Coleman Leukemia Research Fund. Additional grant support for participating institutions is listed in the online Appendix. J.C.B. is a Clinical Scholar of the Leukemia and Lymphoma Society of America.

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

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