title: Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting.
abstract: Autologous hematopoietic cell transplantation (HCT) followed by nonmyeloablative allogeneic HCT (auto/alloHCT) provides cytoreduction and graft-versus-myeloma effects. We report on long-term outcomes of 102 patients with multiple myeloma who received auto/alloHCT with a median follow-up of 6.3 years. Treatment consisted of high-dose melphalan and autograft followed by 2-Gy total body irradiation, with or without fludarabine, and alloHCT from human leukocyte antigen-identical siblings. Postgrafting immunosuppressive agent was cyclosporine or tacrolimus and mycophenolate mofetil. Forty-two percent of patients developed grade 2 to 4 acute graft-versus-host disease (GVHD) and 74% extensive chronic GVHD. Five-year nonrelapse mortality after allografting was 18%, 95% related to GVHD or infections. Among 95 patients with detectable disease, 59 achieved complete remissions. Median time to progression was 5 years. Median overall survival (OS) was not reached. Median progression-free survival (PFS) was 3 years. Five-year OS and PFS were 64% and 36%, respectively. Seventy-three patients receiving autoHCT within 10 months from treatment initiation had 5-year OS of 69% and PFS of 37%. In multivariate analysis, beta-2-microglobulin of more than 3.5 microg/mL at diagnosis and auto/alloHCT more than 10 months after treatment initiation correlated with shorter OS (P = .03 and P = .02) and PFS (P = .04 and P = .03), whereas Karnofsky scores less than 90% at allotransplantation correlated with shorter PFS only (P = .005). Long-term disease control and GVHD remain key issues.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Marcello
authors.initials: M
authors.lastname: Rotta
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Firoozeh
authors.initials: F
authors.lastname: Sahebi
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Thoralf
authors.initials: T
authors.lastname: Lange
authors.forename: Edward D
authors.initials: ED
authors.lastname: Agura
authors.forename: Peter A
authors.initials: PA
authors.lastname: McSweeney
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hari
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.forename: William
authors.initials: W
authors.lastname: Bensinger
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Rainer F
authors.initials: RF
authors.lastname: Storb
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007239:Infections / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014182:Transplantation, Autologous / Q000009:adverse effects; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects