title: Long-term follow-up of recipients of combined human leukocyte antigen-matched bone marrow and kidney transplantation for multiple myeloma with end-stage renal disease.
abstract: BACKGROUND
  Specific tolerance after combined kidney and bone marrow transplantation for multiple myeloma with end-stage renal disease through mixed lymphohematopoietic chimerism has been achieved, as evidenced by prolonged normal renal function without ongoing immunosuppression.
  
  
  METHODS
  To achieve potent antimyeloma responses and induce tolerance for the renal allograft, seven patients (median age: 48 years [range: 34-55 years]) with multiple myeloma and end-stage renal disease underwent a combined human leukocyte antigen-matched kidney and bone marrow transplant with lead follow-up time of more than 12 years. Preparative therapy for the transplant consisted of high-dose cyclophosphamide, equine antithymocyte globulin and pretransplant thymic irradiation. Cyclosporine as the sole posttransplant immunosuppressive therapy was tapered and discontinued as early as day 73 posttransplant.
  
  
  RESULTS
  All seven patients achieved mixed chimerism. One patient developed acute graft-versus-host disease and two chronic graft-versus-host disease. Five of seven patients are alive, four with no evidence of myeloma from 4 to 12.1 years posttransplant. Three patients have normal or near-normal renal function without needing systemic immunosuppression. Two patients with normal renal function off immunosuppression were returned to immunosuppressive therapy without evidence of rejection because of the occurrence of chronic graft-versus-host disease.
  
  
  CONCLUSIONS
  These long-term follow-up data show that sustained renal allograft tolerance and prolonged antimyeloma responses are achievable after human leukocyte antigen-matched kidney and bone marrow transplantation and the induction of mixed lymphohematopoietic chimerism.
authors.affiliation: Department of Medicine, Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, MA 02114, USA. tspitzer@partners.org
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
authors.forename: Nina
authors.initials: N
authors.lastname: Tolkoff-Rubin
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kawai
authors.forename: Steven L
authors.initials: SL
authors.lastname: McAfee
authors.forename: Bimalangshu R
authors.initials: BR
authors.lastname: Dey
authors.forename: Karen
authors.initials: K
authors.lastname: Ballen
authors.forename: Francis
authors.initials: F
authors.lastname: Delmonico
authors.forename: Susan
authors.initials: S
authors.lastname: Saidman
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: A Benedict
authors.initials: AB
authors.lastname: Cosimi
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006650:Histocompatibility Testing; D006801:Humans; D007108:Immune Tolerance; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000276:immunology* / Q000601:surgery; D014184:Transplantation, Homologous