title: Nonmyeloablative hematopoietic stem cell transplantation corrects the disease phenotype in the canine model of leukocyte adhesion deficiency.
abstract: OBJECTIVE
  The aim of this study was to test a nonmyeloablative hematopoietic stem cell transplant regimen applicable to children with leukocyte adhesion deficiency (LAD) who have a histocompatible sibling donor by using the canine model of LAD, namely canine leukocyte adhesion deficiency or CLAD.
  
  
  METHODS
  Thirteen CLAD pups received a hematopoietic stem cell transplant from a dog leukocyte antigen (DLA)-matched littermate donor after pretransplant nonmyeloablative conditioning with 200 cGy total-body irradiation and posttransplant immunosuppression with cyclosporine and mycophenolate mofetil. Donor chimerism following transplant was assessed by flow cytometry for the presence of donor CD18 peripheral blood leukocytes and leukocyte subsets.
  
  
  RESULTS
  Eleven of the 13 transplanted animals achieved stable mixed donor chimerism and reversal of the severe CLAD phenotype without graft-vs-host disease. The level of donor chimerism ranged from 3.9 to 95.5% at 1 year following transplant. There was one early death 3 weeks after transplant from thrombocytopenia and hemorrhage, and one dog with donor microchimerism (0.5% CD18+ donor leukocytes) who had attenuation of the CLAD phenotype.
  
  
  CONCLUSIONS
  These results demonstrate that a nonmyeloablative transplant regimen from a DLA-matched littermate donor leads to mixed chimerism and reversal of the severe disease phenotype in dogs with CLAD, and provides support for the use of this approach in children with LAD who possess a histocompatible sibling donor.
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1203, USA. bauert@mail.nih.gov
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bauer
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Gu
authors.forename: Laura M
authors.initials: LM
authors.lastname: Tuschong
authors.forename: Tanya
authors.initials: T
authors.lastname: Burkholder
authors.forename: John D
authors.initials: JD
authors.lastname: Bacher
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Starost
authors.forename: Robert E
authors.initials: RE
authors.lastname: Donahue
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sokolic
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D018380:Hematopoietic Stem Cell Transplantation; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000628:therapy*; D010641:Phenotype