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Final outcomes of escalated melphalan 280 mg/m2 with amifostine cytoprotection followed autologous hematopoietic stem cell transplantation for multiple myeloma: high CR and VGPR rates do not translate into improved survival

Bone Marrow Transplantation (2018) | Download Citation


The most common preparative regimen for autologous transplantation (ASCT) in myeloma (MM) consists of melphalan 200 mg/m2 (MEL 200). Higher doses of melphalan 220–260 mg/m2, although relatively well tolerated, have not shown significant improvement in clinical outcomes. Several approaches have been pursued in the past to improve CR rates, including poly-chemotherapy preparative regimens, tandem ASCT, consolidation, and/or maintenance therapy. Since there is a steep dose–response effect for intravenous melphalan, we evaluated an alternative single ASCT strategy using higher-dose melphalan at 280 mg/m2 (MEL 280) with amifostine as a cytoprotectant as the maximum tolerated dose determined in an earlier phase I dose escalation trial. We report the final long-term outcomes of MM patients who underwent conditioning with MEL 280 with amifostine cytoprotection followed by ASCT. Although the complete response rate was quite high in the era pre-dating the routine use of novel therapies (proteasome inhibitors, immunomodulatory agents) (49%), the progression-free survival was a disappointing 22 months. The implications of this dichotomy between the excellent depth of ASCT response and progression-free survival are discussed.

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Author information


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

    • Parameswaran Hari
    •  & Jasleen Randhawa
  2. Princess Margaret Hospital, Toronto, ON, Canada

    • Donna E. Reece
  3. Thomas Jefferson University, Philadelphia, PA, USA

    • Neal Flomenberg
    •  & Joanne Filicko-Ohara
  4. Wake Forest Baptist Medical Center Wake Forest, Winston-Salem, NC, USA

    • Dianna S. Howard
    •  & Gordon L. Phillips
  5. University of Maryland, Baltimore, MD, USA

    • Ashrof Z. Badros
    •  & Aaron P. Rapoport
  6. DeCesaris Cancer Institute, Anne Arundel Medical Center, Annapolis, MD, USA

    • Barry R. Meisenberg
  7. John Theurer Cancer Center at Hackensack UMC, Hackensack, NJ, USA

    • David H. Vesole


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The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to David H. Vesole.

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