Kinetics of T-cell development of umbilical cord blood transplantation in severe T-cell immunodeficiency disorders

Background: Hematopoietic stein-cell transplantation is the treatment of ch oice for severe primary T-cell immunodeficiencies. When an HLA-identical si bling donor is not available, an alternative donor stem-cell source is need ed. In primary T-cell immunodeficiencies, T-cell-depleted HLA-haploidentica l bone marrow transplantation has been particularly successful in reconstit uting the T-cell immune system in many of the severe combined immunodeficie ncy syndrome types. However, there are some problems associated with this p reparation as a stem donor source, such as increased resistance to engraftm ent, a long period of time for T-cell engraftment to occur, and failure to engraft B cells and B-cell functions. These problems can be especially trou blesome if the patient is infected before the transplantation. Objective: Umbilical cord blood was evaluated as a stem-cell source for imm une reconstitution in children with severe primary T-cell immunodeficiency disorders, such as severe combined immunodeficiency syndrome, reticular dys genesis, thymic dysplasia, and combined immunodeficiency disease, when a ma tched sibling donor was unavailable, Methods: From January 1996 through July 1997, 6 children received unrelated cord blood stem-cell transplantation after a preparative regimen for the t reatment of combined immunodeficiency diseases, The patients ranged in age from 2 weeks to 6 gears. The cord blood units mere 3 of 6 HLA antigen match es in 2 children, 4 of 6 HLA antigen matches in 3 children, and 5 of 6 HLA antigen matches in 1 child, with molecular HLA-DR mismatch in 3 of the chil dren, Results: The average time for neutrophil engraftment (absolute neutrophil c ount, >500/mm(3)) was 12 days (range, 10 to 15 days), and the average time for platelet engraftment (platelet count, >20,000/mm(3)) was 36 days (range , 24 to 50 days). In a patient with reticular dysgenesis, the first transpl ant failed to engraft but fully engrafted after a second unrelated donor co rd blood transplantation. Five of 6 patients exhibited grade I graft-versus -host disease (GvHD), although 1 child experienced grade IV skin and gut Gv HD. Immunologic reconstitution demonstrated that cord blood stem-cell trans plantation resulted in consistent and stable T-cell, B-cell, and natural ki ller-cell development. The kinetics of recovery of phenotypic expression an d function of T cells occurred between 60 to 100 days and that of natural k iller cells at approximately 180 days. B cells engrafted early, and a study of functional B-cell antibody responses revealed that 2 of 2 patients in w hom intravenous immune globulin was discontinued have low detectable antibo dy responses to tetanus and diphtheria toroid immunizations more than 1 gea r after the transplantation. Conclusions: Unrelated umbilical donor cord blood is an excellent source of stem cells for transplantation of children with immune deficiency disorder s. Benefits include rapid and reliable recovery of immune function, low ris k of GvHD, and low viral transmission rate.