Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency.
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.
Qasim
Waseem
W
Great Ormond Street Hospital and Institute of Child Health, 30 Guilford St, London WC1N 1EH, United Kingdom. w.qasim@ich.ucl.ac.uk
Cavazzana-Calvo
Marina
M
Davies
E Graham
EG
Davis
Jeffery
J
Duval
Michel
M
Eames
Gretchen
G
Farinha
Nuno
N
Filopovich
Alexandra
A
Fischer
Alain
A
Friedrich
Wilhelm
W
Gennery
Andrew
A
Heilmann
Carsten
C
Landais
Paul
P
Horwitz
Mitchell
M
Porta
Fulvio
F
Sedlacek
Petr
P
Seger
Reinhard
R
Slatter
Mary
M
Slatten
Mary
M
Teague
Lochie
L
Eapen
Mary
M
Veys
Paul
P
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