title: Depletion of alloreactive T cells for tolerance induction in a recipient of kidney and hematopoietic stem cell transplantations.
abstract: The present case report represents a successful attempt to induce transplantation tolerance to organ allograft by combined administration of donor hematopoietic cells and kidney based on in vivo deletion of alloreactive host-vs-graft and graft-vs-host alloreactive T cells following non-myeloablative conditioning. We were able to induce mixed and eventually full donor chimerism and tolerance of kidney allograft in a 15-yr-old male with ESRD after cisplatin treatment and autologous HSCT for mediastinal germ cell tumor. Our approach to induce tolerance was based on preferential depletion of alloreactive T cells induced by exposure to donor's alloantigens and administration of cyclophosphamide at day 2 and day 3 after stem cell infusion. Additional non-specific immunosuppression as part of the conditioning included exposure to two fractions of TLI, treatment with alemtuzumab (monoclonal anti-CD52) and short-term conventional IS treatment to avoid early graft loss, because of request of IRB. Using this approach, with rapid tapering of all conventional IS treatment, the patient maintains good renal functions without evidence of both acute and chronic rejection for 32 months off all medications.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Kanchana
authors.initials: K
authors.lastname: Tangnararatchakit
authors.forename: Wiwat
authors.initials: W
authors.lastname: Tirapanich
authors.forename: Usanarat
authors.initials: U
authors.lastname: Anurathapan
authors.forename: Wiwat
authors.initials: W
authors.lastname: Tapaneya-Olarn
authors.forename: Samart
authors.initials: S
authors.lastname: Pakakasama
authors.forename: Saengsuree
authors.initials: S
authors.lastname: Jootar
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
authors.forename: Suradej
authors.initials: S
authors.lastname: Hongeng
mesh_terms: D000293:Adolescent; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D000074301:CD52 Antigen; D002945:Cisplatin / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis; D006084:Graft Rejection; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000628:therapy; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D002945:Cisplatin