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Cytoreduction Regimens

Activity of single-agent melphalan 220–300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma

Bone Marrow Transplantation volume 33, pages 781–787 (2004)Cite this article

Summary:

High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220–300 mg/m2 plus amifostine (AF) cytoprotection and AHSCT as part of a phase I–II trial. Median age was 51 years (range 24–62 years); NHL histology was varied, but was aggressive (including transformed from indolent) in 19 patients, indolent in two patients and mantle cell in one. All 26 patients had been extensively treated; 11 were refractory to the immediate prior therapy on protocol entry and two had undergone prior AHSCT. All were deemed ineligible for other, ‘first-line’ AHSCT regimens. Of these 26 patients, 22 survived to initial tumor evaluation on D +100. At this time, 13 were in complete remission, including four patients who were in second CR before HDMEL+AF+AHSCT. Responses occurred at all HDMEL doses. Currently, seven patients are alive, including five without progression, with a median follow-up in these latter patients of D +1163 (range D +824 to D +1630); one of these patients had a nonmyeloablative allograft as consolidation on D +106. Conversely, 14 patients relapsed or progressed, including five who had previously achieved CR with the AHSCT procedure. Two patients, both with HL, remain alive after progression; one is in CR following salvage radiotherapy. Six patients died due to nonrelapse causes, including two NHL patients who died while in CR. We conclude that HDMEL+AF+AHSCT has significant single-agent activity in relapsed or refractory NHL and HL. This experience may be used as a starting point for subsequent dose escalation of HDMEL (probably with AF) in established combination regimens.

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Acknowledgements

We thank our patients for their willingness to undergo clinical research studies; our nursing colleagues for their excellent patient care; our medical consultants for their valuable assistance; our data coordinators, and Ms M Coddington, Ms Lynn Stull and Ms Linda Wilkinson for their expert help with manuscript preparation. Finally, we thank Dr J Friedberg for his helpful suggestions with the manuscript. Grant support for this study was provided by the NIH, RO3CA80666 and ALZA.

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Authors and Affiliations

  1. Blood and Marrow Transplant Program, University of Kentucky, Lexington, KY, USA

    G L Phillips, D E Reece, V R Adams, G A Hale, D S Howard, A Kniska, K W Marshall & R Nath

  2. Blood and Marrow Transplant Program, Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

    G L Phillips, B R Meisenberg, A Z Badros, R G Fenton, B Mookerjee, A P Rapoport, C Sarkodee-Adoo & N Takebe

  3. Jefferson Medical College, Philadelphia, PA, USA

    J L Brunner, J Filicko, D L Grosso, D H Vesole, J L Wagner & N Flomenberg

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

    V P Johnson, A Kniska & N Flomenberg

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Correspondence to G L Phillips.

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Phillips, G., Meisenberg, B., Reece, D. et al. Activity of single-agent melphalan 220–300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma. Bone Marrow Transplant 33, 781–787 (2004). https://doi.org/10.1038/sj.bmt.1704424

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