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Conditioning

A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 52, pages 59–65 (2017)Cite this article

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Abstract

Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission. Seventy-one patients (median age: 56 years) received CloBu4. At day 30 after HCT, 90% achieved morphologic remission. The incidence of non-relapse mortality and relapse at 2 years was 25% and 55%, respectively. The 2-year overall survival (OS) and event-free survival (EFS) were 26% and 20%, respectively. Patients entering HCT in PIF had significantly greater EFS than those in relapse (34% vs 8%; P<0.01). Multivariate analysis comparing CloBu4 with a contemporaneous cohort (Center for International Blood and Marrow Transplantation Research) of AML not in remission receiving other myeloablative conditioning (n=105) demonstrated similar OS (HR: 1.33, 95% confidence interval: 0.92–1.92; P=0.12). HCT with myeloablative CloBu4 is associated with high early response rates and may produce durable remissions in select patients with AML not in remission.

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Acknowledgements

We wish to acknowledge Otsuka Pharmaceutical Co., Ltd. and Sanofi-Aventis U.S. LLC for providing research support to cover the costs of conducting this clinical trial. Sanofi-Aventis also provided clofarabine at no charge.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    J Magenau, B Parkin, T Churay & S Lieland

  2. Washington University, St. Louis, MO, USA

    P Westervelt

  3. City of Hope, Duarte, CA, USA

    S Khaled & S Forman

  4. University of Kansas, Westwood, KS, USA

    S Khaled, J McGuirk & S Forman

  5. Medical College of Wisconsin, Milwaukee, WI, USA

    P Hari & M Eapen

  6. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    P S Becker & B Scott

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

    T Braun

  8. Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA

    B Logan & H Wang

  9. Vanderbilt University, Nashville, TN, USA

    M Jagasia

  10. Hackensack University Medical Center, Hackensack, NJ, USA

    S D Rowley

  11. Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada

    D D H Kim

  12. Hospital for Sick Children, Toronto, Ontario, Canada

    T Schechter

  13. University of Pennsylvania, Philadelphia, PA, USA

    N Frey

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

    S Mineishi

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  1. J Magenau
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Corresponding author

Correspondence to J Magenau.

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Competing interests

HP has received honoraria and has served in as a consultant for Sanofi. The remaining authors declare no conflict of interest. This was an investigator initiated trial with Research Support provided by Otsuka Pharmaceutical Co., Ltd. and Sanofi-Aventis U.S. LLC. The authors are solely responsible for the design, data collection, analysis and decision to publish this trial.

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Magenau, J., Westervelt, P., Khaled, S. et al. A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 52, 59–65 (2017). https://doi.org/10.1038/bmt.2016.188

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