title: Long-term outcome of myeloablative allogeneic stem cell transplantation for multiple myeloma.
abstract: Allogeneic stem cell transplantation (alloSCT) has been used in the hopes of harnessing the curative potential of the graft-versus-myeloma effect. This study examines the long-term outcomes of a large cohort of patients with myeloma who were treated with myeloablative alloSCT at a single center. Comparisons are made with those who were treated with autologous stem cell transplantation (ASCT). Between January 1989 and February 2002, 158 patients age<or=55 years underwent SCT for myeloma. Seventy-two patients underwent myeloablative alloSCT (58 related; 14 unrelated), whereas 86 patients underwent ASCT. Most patients received single-agent high dose dexamethasone or VAD (vincristine, adriamycin, dexamethasone) therapy pre-SCT. Conditioning regimens were melphalan-based for all ASCT patients, whereas the alloSCT patients received melphalan-based (70%), total-body irradiation (TBI)-based (18%), or other (13%). Patients who underwent alloSCT were younger, had a higher Durie-Salmon stage disease, and a shorter median time from diagnosis to transplant. Myeloma subtypes were similar between groups. Other pre-SCT (BMT) characteristics were similar except that ASCT patients had a higher proportion of cases that received palliative radiotherapy pre-SCT. Disease response pre-SCT was similar. At last follow-up, 61 of 158 patients are alive with a median follow-up of 88.4 months (range: 35.5-208.5). The overall survival (OS) of the alloSCT cohort was 48.1% at 5 years and 39.9% at 10 years compared to 46.2% at 5 years and 30.8% at 10 years for the ASCT cohort (P=.94). The event-free survival of the alloSCT cohort was 33.3% at 5 years and 31.4% at 10 years compared to 32.9% and 15.2%for the ASCT cohort (P=.64). Treatment-related mortality (TRM) at 1 year was 22% for the alloSCT cohort and 14% in the ASCT cohort (P=.21). Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 72% and the cumulative incidence of chronic GVHD (cGVHD) was 68% at 2 years. Neither aGVHD nor cGVHD had an influence on OS or event-free survival, although 5 of 14 patients who have received donor lymphocyte infusions (DLI) have had disease response. The risk of relapse was reduced in those who developed aGVHD (P=.02) but not cGVHD (P=.23). In conclusion, although there are patient who are alive without disease>10 years post myeloablative alloSCT, similarly there are long-term survivors post-ASCT. Myeloablative alloSCT should not be considered standard treatment, and should only be considered in the context of a clinical trial.
authors.affiliation: The Leukemia/Bone Marrow Transplantation Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency and the University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Kuruvilla
authors.forename: John D
authors.initials: JD
authors.lastname: Shepherd
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Sutherland
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Nevill
authors.forename: Janet
authors.initials: J
authors.lastname: Nitta
authors.forename: Aulan
authors.initials: A
authors.lastname: Le
authors.forename: Donna L
authors.initials: DL
authors.lastname: Forrest
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hogge
authors.forename: Julye C
authors.initials: JC
authors.lastname: Lavoie
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Nantel
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Toze
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Smith
authors.forename: Micheal J
authors.initials: MJ
authors.lastname: Barnett
authors.forename: Kevín W
authors.initials: KW
authors.lastname: Song
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous