Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma

Author:

Maloney David G.1,Molina Arthur J.1,Sahebi Firoozeh1,Stockerl-Goldstein Keith E.1,Sandmaier Brenda M.1,Bensinger William1,Storer Barry1,Hegenbart Ute1,Somlo George1,Chauncey Thomas1,Bruno Benedetto1,Appelbaum Frederick R.1,Blume Karl G.1,Forman Stephen J.1,McSweeney Peter1,Storb Rainer1

Affiliation:

1. From the Fred Hutchinson Cancer Research Center, University of Washington, and VA Medical Center, Seattle; City of Hope National Medical Center, Duarte, CA; Stanford University Medical Center, Stanford, CA; University of Colorado, Denver; University of Leipzig, Germany; and University of Torino, Italy.

Abstract

AbstractThe full potential of a graft-versusmyeloma effect after allogeneic hematopoietic cell transplantation (HCT) for patients with multiple myeloma (MM) has not been realized because of excessive early transplantation-related mortality (TRM) with conventional HCT. Autologous HCTs have been characterized by almost universal disease recurrences. The current trial combined autologous HCT with subsequent nonmyeloablative allogeneic HCT to maintain the benefits of both approaches with acceptable toxicity. Fifty-four patients, 52 years of age (median; range, 29-71 years), with previously treated stage II or III MM (52% refractory or relapsed disease) were given melphalan 200 mg/m2 and autologous HC transplants. Regimen-related toxicities after autologous HCT were moderate with a median of 6 days of neutropenia, 7 days of hospitalization, and 1 death from infection. Forty to 229 days later (median, 62 days), 52 patients received a single fraction dose of 2 Gy total body irradiation and HC transplants from HLA-identical siblings with postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Patients experienced medians of 0 days of hospitalization, neutropenia, and thrombocytopenia. Sustained engraftment was uniform. With a median follow-up of 552 days after allografting, overall survival is 78%. One patient (2%) died before day 100 from disease progression. Thirty-eight percent of patients developed acute graft-versus-host disease (GVHD; grade II in all but 4 cases) and 46% chronic GVHD requiring therapy. Tumor responses occurred slowly. Thus far, 57% of patients have achieved complete remissions and 26% have achieved partial remissions for an overall response of 83%. Despite being evaluated in elderly patients with MM, this 2-step approach has reduced the acute toxicities of allogeneic HCT while achieving potent antitumor activities.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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