title: Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma.
abstract: The full potential of a graft-versus-myeloma 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.
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, and VA Medical Center, Seattle, USA. dmaloney@fhcrc.org
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Molina
authors.forename: Firoozeh
authors.initials: F
authors.lastname: Sahebi
authors.forename: Keith E
authors.initials: KE
authors.lastname: Stockerl-Goldstein
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: William
authors.initials: W
authors.lastname: Bensinger
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.forename: Thomas
authors.initials: T
authors.lastname: Chauncey
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Karl G
authors.initials: KG
authors.lastname: Blume
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Peter
authors.initials: P
authors.lastname: McSweeney
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014182:Transplantation, Autologous / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents