Umbilical Cord Blood Stem Cell Transplantation in Severe T-Cell Immunodeficiency Disorders

Hematopoietic stem cell transplantation is the treatment of choice for severe primary T-cell immunodeficiencies. When an HLA-identical sibling as the donor is not available, an alternative donor stem cell source is needed. In primary T-cell immunodeficiencies, T-cell–depleted HLA-haploidentical bone marrow transplantation has been particularly successful in reconstituting the immune system in many but not all of the severe T-cell immune deficiency disorders. This study reports the use of umbilical cord blood (UCB) stem cell transplantation in 16 patients with severe T cell immune deficiency disorders. UCB was evaluated as a stem cell source for immune reconstitution in children with severe primary T-cell immunodeficiency disorders, such as severe combined immunodeficiency syndrome (SCID), reticular dysgenesis, thymic dysplasia, combined immunodeficiency disease (CID), and Wiskott-Aldrich syndrome (WAS) when an HLA-matched sibling donor was unavailable. From 1996 through 2004, 16 children diagnosed with severe T-cell immunodeficiencies received allogeneic, unrelated cord blood stem cell transplantation. Initially, the preparative regimen consisted of ablative doses of busulfan, with either cyclophosphamide or fludarabine and ATG; subsequently a non-myeloablative regimen consisting of fludarabine, cyclophosphamide and ATG was used. All patients with WAS received a myeloablative preparative regimen. Twelve of 16 patients engrafted and are alive with a mean of 6.5 ± 2.6 years (mean ± standard deviation [SD]) posttransplantation. Four patients died, two from veno-occlusive disease, one from sepsis, and one from chronic graft-versus-host disease (GVHD) and sepsis. Acute GVHD was observed in 12 patients; 6 patients with grade I–II and 6 with grade III–IV acute GVHD. Only one patient in our series experienced chronic GVHD. The median time for neutrophil and platelet engraftment was 12 ± 2 was 33 ± 5 days, respectively. Cord blood stem cell transplantation resulted in consistent and stable T, B and NK cell numbers and functions. Measurable T-cell numbers were seen between 60 to 100 days. Initial T-cell engraftment consisted predominantly of memory T cells, and at 12 to 24 months changed to naive T cells, indicating de novo maturation of T cells. Natural killer (NK) cells developed at approximately 6 months. B-cell engraftment was present by 4 months posttransplantation; antibody responses were detected after intravenous immune globulin (IVIG) was discontinued after immunizations with tetanus and diphtheria toxoids and Hemophilus influenzae type B at 18 to 24 months posttransplantation. Unrelated umbilical donor cord blood is an alternative source of stem cells for transplantation in children with severe T-cell immune deficiency disorders when a suitable HLA-matched donor is not available. Benefits of UCB include rapid and reliable development of T-, NK-, and B-cell immune functions. (Pediatr Asthma Allergy Immunol 2005; 18[4];189–200.)