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Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission

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Abstract

The optimal intensity of conditioning for allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) remains undefined. Traditionally, myeloablative conditioning regimens improve disease control, but at the risk of greater nonrelapse mortality. Because fludarabine with myeloablative doses of intravenous busulfan using pharmacokinetic monitoring has excellent tolerability, we reasoned that this regimen would limit relapse without substantially elevating toxicity when compared to reduced intensity conditioning. We retrospectively analyzed 148 consecutive AML patients in remission receiving T cell replete HCT conditioned with fludarabine and intravenous busulfan at doses defined as reduced (6.4 mg/kg; FluBu2, n = 63) or myeloablative (12.8 mg/kg; FluBu4, n = 85). Early and late nonrelapse mortality (NRM) was similar among FluBu4 and FluBu2 recipients, respectively (day + 100: 4 vs 0 %; 5 years: 19 vs 22 %; p = 0.54). NRM did not differ between FluBu4 and FluBu2 in patients >50 years of age (24 vs 22 %, p = 0.75). Relapse was lower in recipients of FluBu4 (5 years: 30 vs 49 %; p = 0.04), especially in patients with poor risk cytogenetics (22 vs 59 %; p = 0.02) and those >50 years of age (28 vs 51 %; p = 0.02). Overall survival favored FluBu4 recipients at 5 years (53 vs 34 %, p = 0.02), a finding confirmed in multivariate analysis (HR: 0.57; 95 % CI: 0.34–0.95; p = 0.03). These data suggest that myeloablative FluBu4 may provide equivalent NRM, reduced relapse, and improved survival compared to FluBu2, emphasizing the importance of busulfan dose in conditioning for AML.

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Acknowledgments

We sincerely thank the patients who participated in this research. We also thank the physician assistants, nurse practitioners, BMT nurses, and coordinators for their devotion to patient care. Diane Klann assisted in review of HLA typing data. J.M. is supported by an ASBMT New Investigator Award.

Authorship contributions

J.M. and S.G. treated patients, designed and planned the study, analyzed data, and wrote the manuscript; T.B. and Y.L. were the study statisticians; T.C was the data manager. B.P., S.C., P.R., A.P., M.R., D.B., S.M., C.K., G.Y., D.F., A.H., J.L., and D.C. treated patients, contributed to quality control of the clinical endpoints, participated in research discussions, and/or manuscript editing.

Conflict of interest

The authors report no conflicts of interest.

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  1. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

    John M. Magenau, Pavan Reddy, Brian Parkin, Attaphol Pawarode, Sung Choi, John Levine, Gregory Yanik, Carrie Kitko, Tracey Churay, David Frame, Mary Mansour Riwes, Andrew Harris, Dale Bixby, Daniel R. Couriel & Steven C. Goldstein

  2. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA

    Thomas Braun & Yumeng Li

  3. University of Alabama at Birmingham, Birmingham, AL, USA

    Shin Mineishi

  4. Blood and Marrow Transplant Program, Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, F4860 University Hospital South, Ann Arbor, MI, 48109-5932, USA

    John M. Magenau

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Magenau, J.M., Braun, T., Reddy, P. et al. Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission. Ann Hematol 94, 1033–1041 (2015). https://doi.org/10.1007/s00277-015-2349-4

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