title: Nonmyeloablative unrelated donor hematopoietic cell transplantation to treat patients with poor-risk, relapsed, or refractory multiple myeloma.
abstract: The purpose of this study was to determine long-term outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in patients with poor-risk multiple myeloma. A total of 24 patients were enrolled; 17 patients (71%) had chemotherapy-refractory disease, and 14 (58%) experienced disease relapse or progression after previous autologous transplantation. Thirteen patients underwent planned autologous transplantation followed 43-135 days later with unrelated transplantation, whereas 11 proceeded directly to unrelated transplantation. All 24 patients were treated with fludarabine (90 mg/m(2)) and 2 Gy of total body irradiation before HLA-matched unrelated peripheral blood stem cell transplantation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median follow-up was 3 years after allografting. One patient experienced nonfatal graft rejection. The incidences of acute grades II and III and chronic graft-versus-host disease were 54%, 13%, and 75%, respectively. The 3-year nonrelapse mortality (NRM) was 21%. Complete responses were observed in 10 patients (42%); partial responses, in 4 (17%). At 3 years, overall survival (OS) and progression-free survival (PFS) rates were 61% and 33%, respectively. Patients receiving tandem autologous-unrelated transplantation had superior OS and PFS (77% and 51%) compared with patients proceeding directly to unrelated donor transplantation (44% and 11%) (PFS P value = .03). In summary, for patients with poor-risk, relapsed, or refractory multiple myeloma, cytoreductive autologous HCT followed by nonmyeloablative conditioning and unrelated HCT is an effective treatment approach, with low NRM, high complete remission rates, and prolonged disease-free survival.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, D1-100, Seattle, WA 98109, USA. ggeorges@fhcrc.org
authors.forename: George E
authors.initials: GE
authors.lastname: Georges
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Thoralf
authors.initials: T
authors.lastname: Lange
authors.forename: Edward D
authors.initials: ED
authors.lastname: Agura
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Peter A
authors.initials: PA
authors.lastname: McSweeney
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: Marco
authors.initials: M
authors.lastname: Mielcarek
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000328:Adult; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000145:classification; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D011379:Prognosis; D018570:Risk Assessment; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome