title: Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: in vivo and in vitro analyses.
abstract: Six patients with renal failure due to multiple myeloma (MM) received simultaneous kidney and bone marrow transplantation (BMT) from HLA-identical sibling donors following nonmyeloablative conditioning, including cyclophosphamide (CP), peritransplant antithymocyte globulin and thymic irradiation. Cyclosporine (CyA) was given for approximately 2 months posttransplant, followed by donor leukocyte infusions. All six patients accepted their kidney grafts long-term. Three patients lost detectable chimerism but accepted their kidney grafts off immunosuppression for 1.3 to >7 years. One such patient had strong antidonor cytotoxic T lymphocyte (CTL) responses in association with marrow rejection. Two patients achieved full donor chimerism, but resumed immunosuppression to treat graft-versus-host disease. Only one patient experienced rejection following CyA withdrawal. He responded to immunosuppression, which was later successfully withdrawn. The rejection episode was associated with antidonor Th reactivity. Patients showed CTL unresponsiveness to cultured donor renal tubular epithelial cells. Initially recovering T cells were memory cells and were enriched for CD4+CD25+ cells. Three patients are in sustained complete remissions of MM, despite loss of chimerism in two. Combined kidney/BMT with nonmyeloablative conditioning can achieve renal allograft tolerance and excellent myeloma responses, even in the presence of donor marrow rejection and antidonor alloresponses in vitro.
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, MGH East, Building 149-5102 13th Street, Boston, Massachusetts, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Fudaba
authors.forename: T R
authors.initials: TR
authors.lastname: Spitzer
authors.forename: J
authors.initials: J
authors.lastname: Shaffer
authors.forename: T
authors.initials: T
authors.lastname: Kawai
authors.forename: T
authors.initials: T
authors.lastname: Fehr
authors.forename: F
authors.initials: F
authors.lastname: Delmonico
authors.forename: F
authors.initials: F
authors.lastname: Preffer
authors.forename: N
authors.initials: N
authors.lastname: Tolkoff-Rubin
authors.forename: B R
authors.initials: BR
authors.lastname: Dey
authors.forename: S L
authors.initials: SL
authors.lastname: Saidman
authors.forename: A
authors.initials: A
authors.lastname: Kraus
authors.forename: T
authors.initials: T
authors.lastname: Bonnefoix
authors.forename: S
authors.initials: S
authors.lastname: McAfee
authors.forename: K
authors.initials: K
authors.lastname: Power
authors.forename: K
authors.initials: K
authors.lastname: Kattleman
authors.forename: R B
authors.initials: RB
authors.lastname: Colvin
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.forename: A B
authors.initials: AB
authors.lastname: Cosimi
authors.forename: M
authors.initials: M
authors.lastname: Sykes
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery*; D016030:Kidney Transplantation; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications*; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents