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Access through your institution Buy or subscribe Leukocyte adhesion deficiency (LAD) is an autosomal recessive disorder characterized by impaired migration of cells of the innate immune
system, primarily neutrophils, from the intravascular space.1 This migratory defect stems from impaired adhesion of marginated neutrophils to the vascular endothelium, thereby pre-empting
neutrophil diapedesis and localized antimicrobial activity. Normally, stable neutrophil adhesion is mediated by interactions between _β_2 leukocyte integrins (CD11/CD18) and counter ligands
of the intercellular adhesion molecule family inducibly expressed on endothelial cell surfaces at inflammatory foci.2 Leukocyte adhesion deficiency syndromes stem from dysfunction of
neutrophil migration. Three forms of LAD have been described.3 LAD1, the predominant form, stems from absent or severely impaired CD18 expression, preventing the stable leukocyte–endothelial
engagement necessary for neutrophil egress from microvasculature. Severe LAD, regardless of the molecular defect, results in frequent and potentially fatal infections. The treatment of LAD
has been problematic. Although intense antibiotic therapy and granulocyte transfusion are used during acute infectious episodes, children with LAD frequently die from infectious sequelae
during the first 5 years of life.4 Although retrovirus-mediated gene therapy has been attempted, the only curative treatment for LAD is allogeneic stem cell transplant (SCT). Pre-clinical
data suggest that donor chimerism of only 5% may be sufficient to protect patients with LAD from recurrent pyogenic infections post transplant.5, 6, 7, 8 As such, strategies that maximize
the probability of engraftment and donor tolerance while minimizing toxicity may be particularly efficacious in definitive LAD treatment. The patient is a 20-year-old male, diagnosed shortly
after birth with LAD, following delayed umbilical cord scission and concurrent omphalitis with _Pseudomonas_ sepsis. Early disease manifestations included recurrent sinopulmonary infections
and persistent skin ulcerations of the extremities, groin, scrotum and perirectal areas. Aggressive supportive care measures included surgical debridement, maggot instillation and split
thickness skin grafting. The patient was regularly hospitalized for serious bacterial infections, and on several occasions required donor leukocyte infusions. An attempt at definitive
therapy was made using retrovirus-mediated CD18 gene replacement, which ultimately was unsuccessful. The patient was referred for SCT as a means of potential cure for LAD1. Pre-transplant
evaluation was significant for dental disease and a 4 cm ulcerated lesion in the groin. A reduced-intensity transplant was planned and approved by the Institutional Review Board at
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using a reduced-intensity conditioning regimen. _Blood_ 2005; 105: 879–885. Article CAS Google Scholar Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Pediatric Stem
Cell Transplant Program, Vanderbilt University, Nashville, TN, USA M E Engel, C Calder, B Manes & H Frangoul * Experimental Transplantation and Immunology Branch, National Cancer
Institute, Bethesda, MD, USA D D Hickstein & T R Bauer Jr Authors * M E Engel View author publications You can also search for this author inPubMed Google Scholar * D D Hickstein View
author publications You can also search for this author inPubMed Google Scholar * T R Bauer Jr View author publications You can also search for this author inPubMed Google Scholar * C Calder
View author publications You can also search for this author inPubMed Google Scholar * B Manes View author publications You can also search for this author inPubMed Google Scholar * H
Frangoul View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Engel, M.,
Hickstein, D., Bauer, T. _et al._ Matched unrelated bone marrow transplantation with reduced-intensity conditioning for leukocyte adhesion deficiency. _Bone Marrow Transplant_ 37, 717–718
(2006). https://doi.org/10.1038/sj.bmt.1705301 Download citation * Published: 20 February 2006 * Issue Date: 01 April 2006 * DOI: https://doi.org/10.1038/sj.bmt.1705301 SHARE THIS ARTICLE
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