Abstract 890
Leukocyte adhesion deficiency (LAD) is an uncommon autosomal recessive condition caused by mutations in the CD18 (β2 integrin) genes. As a result, the leukocytes (WBCs) in severe LAD do not express the CD18-CD11 complex on the cell surface and have defective migration and adherence. Infants with LAD have recurrent or persistent bacterial infections despite leukocytosis and usually die by two years of age. Allogeneic bone marrow transplantation (BMT) is curative in LAD (Thomas C et al., Blood 1995; 86:1629) but is limited by the lack of HLA-matched related donors. Unrelated placental/umbilical cord blood cell (UCBC) transplantation (UCBCT) has been therapeutic in children with other hematologic diseases or with neoplastic, immunologic, or metabolic disorders but has not previously been reported for LAD. We performed an unrelated UCBCT in a 6-month-old male with LAD after pre-transplant busulfan (40 mg/m2 p.o. q6hr × 16 doses), cyclophosphamide (50 mg/kg/day i.v. × 4 days), and anti-thymocyte globulin (30 mg/kg/day × 3 days). The UCBC unit (Placental Blood Program, New York Blood Center, New York, NY) was from a male donor and was mismatched with the pt at one HLA-A locus (donor A24,30; recipient A23,24). The UCBC graft contained 3.7 × 107 nucleated cells/kg and 3.7 × 105 CD34+ cells/kg. Intravenous cyclosporine and methylprednisolone were given as post-UCBCT prophylaxis against acute graft-versus-host disease (GVHD). The total WBC and the absolute neutrophil count exceeded 1.0 × 109/l and 0.5 × 109/l, respectively, at 20 days after UCBCT, but the patient remained platelet transfusion dependent. There was no clinical or laboratory evidence of acute GVHD. Flow cytometric analysis of WBCs at 34 days after UCBCT showed expression of CD18, CD11b and CD11c on all lymphocytes and on 50% of monocytes and granulocytes. Analysis of WBC DNA from that sample, using the variable number of tandem repeat (VNTR) assay, showed partial chimerism with 40-70% donor and 30-60% patient DNA. Despite treatment with cidofovir, the patient died with fulminant adenovirus hepatitis 34 days after UCBCT. These observations provide proof of principle that unrelated UCBCT can lead to reconstitution of normal hematopoiesis with functionally normal leukocytes in LAD. We conclude that fully or partially HLA-matched unrelated UCBCT should be considered in patients with LAD who lack histocompatible related donors.
