title: Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency.
abstract: OBJECTIVE
  Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 beta-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed wound healing. Allogeneic hematopoietic stem-cell transplantation offers the possibility of curative therapy, and with patient numbers at any individual center being limited, we surveyed the transplant experience at 14 centers worldwide.
  
  
  METHODS
  The course of 36 children with a confirmed diagnosis of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research.
  
  
  RESULTS
  At a median follow-up of 62 months (extending to 14 years), the overall survival rate was 75%. Myeloablative conditioning regimens were used in 28 patients, and reduced-intensity conditioning in 8 patients, with no deaths in this subgroup. Survival rates after matched family donor and unrelated donor transplants were similar, with 11 of 14 matched family donor and 12 of 14 unrelated donor recipients alive; mortality was greatest after haploidentical transplants, after which 4 of 8 children did not survive. Twenty-seven transplant recipients were alive, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases.
  
  
  CONCLUSIONS
  Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients.
authors.affiliation: Great Ormond Street Hospital and Institute of Child Health, 30 Guilford St, London WC1N 1EH, United Kingdom. w.qasim@ich.ucl.ac.uk
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
authors.forename: Jeffery
authors.initials: J
authors.lastname: Davis
authors.forename: Michel
authors.initials: M
authors.lastname: Duval
authors.forename: Gretchen
authors.initials: G
authors.lastname: Eames
authors.forename: Nuno
authors.initials: N
authors.lastname: Farinha
authors.forename: Alexandra
authors.initials: A
authors.lastname: Filopovich
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Friedrich
authors.forename: Andrew
authors.initials: A
authors.lastname: Gennery
authors.forename: Carsten
authors.initials: C
authors.lastname: Heilmann
authors.forename: Paul
authors.initials: P
authors.lastname: Landais
authors.forename: Mitchell
authors.initials: M
authors.lastname: Horwitz
authors.forename: Fulvio
authors.initials: F
authors.lastname: Porta
authors.forename: Petr
authors.initials: P
authors.lastname: Sedlacek
authors.forename: Reinhard
authors.initials: R
authors.lastname: Seger
authors.forename: Mary
authors.initials: M
authors.lastname: Slatter
authors.forename: Mary
authors.initials: M
authors.lastname: Slatten
authors.forename: Lochie
authors.initials: L
authors.lastname: Teague
authors.forename: Mary
authors.initials: M
authors.lastname: Eapen
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
mesh_terms: D000293:Adolescent; D016465:Bone Marrow Purging; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000502:physiology; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000401:mortality / Q000628:therapy*; D008297:Male; D009894:Opportunistic Infections / Q000209:etiology; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014775:Virus Activation; D014777:Virus Diseases / Q000209:etiology