title: Serial transplantation resulting in tolerance to an unrelated cord blood graft.
abstract: Unrelated cord blood (UCB) hematopoietic stem cells were serially transplanted into two human leukocyte antigen (HLA)-identical siblings with T cell, B cell, natural killer cell severe combined immunodeficiency. Brother A received a 4/6-matched, HLA DRbeta1-identical but class I-disparate UCB graft after myeloablative dosages of busulfan, melphalan, and antithymocyte globulin. He experienced complete donor chimerism, severe acute gastrointestinal graft-versus-host disease (GVHD), and limited chronic skin GVHD that resolved with treatment. Two years later, brother B received unfractionated marrow from brother A after reduced-intensity conditioning with cyclophosphamide and antithymocyte globulin. Brother B experienced mixed-donor (i.e. original UCB) chimerism and no histologically documented GVHD. Both brothers are clinically well; brother A is in a fully immunologically reconstituted state. The uneventful course and progressive increase in donor chimerism after the second transplantation indicates that hematopoietic cells derived from the older brother's marrow engrafted without causing GVHD, suggesting that acquired tolerance to disparate unrelated HLA antigens was achieved.
authors.affiliation: Department of Pediatrics and the Pediatric Stem Cell Transplantation Program, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN 46202-5200, USA. sgoebel2@iupui.edu
authors.forename: W Scott
authors.initials: WS
authors.lastname: Goebel
authors.forename: Robert P
authors.initials: RP
authors.lastname: Nelson
authors.forename: Zacharie
authors.initials: Z
authors.lastname: Brahmi
authors.forename: Darla J
authors.initials: DJ
authors.lastname: Gowan
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Towell
authors.forename: Kent A
authors.initials: KA
authors.lastname: Robertson
authors.forename: Paul R
authors.initials: PR
authors.lastname: Haut
mesh_terms: D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods*; D002066:Busulfan / Q000627:therapeutic use; D046528:Chimerism; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D003520:Cyclophosphamide / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000628:therapy*; D035781:Siblings; D013601:T-Lymphocytes / Q000276:immunology; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology*
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan; D008558:Melphalan