Originally published as JCO Early Release 10.1200/JCO.2005.06.090 on November 8 2004

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Outcome of Induction and Postremission Therapy in Younger Adults With Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study

From The Ohio State University, Columbus, OH; The Cancer and Leukemia Group B Statistical Center; Duke University, Durham; Wake Forest University, Winston-Salem, NC; Dana-Farber Cancer Institute, Boston, MA; University of Alabama at Birmingham, Birmingham, AL; North Shore University Hospital, Manhasset; Roswell Park Cancer Institute, Buffalo, NY; University of Maryland Cancer Center, Baltimore, MD; University of Chicago, Chicago, IL; and Wayne State University School of Medicine, Detroit, MI

Address reprint requests to Sherif S. Farag, MB, PhD, Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, A433A Starling-Loving Hall, 320 W Tenth Avenue, Columbus, OH 43210; e-mail: farag-1{at}medctr.osu.edu

PURPOSE: Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML).

PATIENTS AND METHODS: In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide ± PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV).

RESULTS: Of 350 patients receiving AD, 73% achieved complete remission (CR), compared with 82% of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P < .001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28% each for intensification groups I and II, compared with 41% and 45% for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62% and 67% for groups I and II, respectively, compared with 54% and 44% for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis.

CONCLUSION: In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation.

Supported in part by grants from the National Cancer Institute to the Cancer and Leukemia Group B (grant Nos. CA101140, CA31946, CA77658, CA33601, CA41287, CA47545, CA03927, CA47577, CA35279, and CA32291), grant No. CA16058, and the Coleman Leukemia Research Fund.

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

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