Umbilical cord blood transplantation in severe T-cell immunodeficiency disorders: Two-year experience

Hematopoietic stem cell transplantation is the treatment of choice for seve re primary T-cell immunodeficiencies. When an HLA-identical sibling as the donor is not available. an alternative donor stem cell sourer 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 deficienc y disorders. This study reports the use of umbilical cord blood (UCB) stem cell transplantation in severe T-cell immune deficiency. Umbilical cord blood was evaluated as a stern cell sourer for immune recons titution in children with severe primary T-cell immunodeficiency disorders, such as severe combined immunodeficiency syndrome (SCID, reticular dysgene sis, thymic dysplasia, combined immunodeficiency disease (CID), and Wiskott -Aldrich syndrome (WAS) when a matched sibling donor was unavailable. From 1/96 through 5/98, eight children received unrelated cord blood stem cell t ransplantation following a preparative regimen for the treatment of combine d immunodeficiency diseases. The patients ranged in age from 2 weeks to 8 y ears. The cord blood units were 3/6 HLA antigen matches in two children, 3/ 6 in four children, and 5/6 in two child, with molecular HLA-DR mismatch in three of the children. The average time for neutrophil engraftment (absolu te neutrophil count >500/mm(3)) was 12 days (range 10-15 days) and the aver age time for platelet engraftment (platelet count >20,000/mm(3)) was 36 day s (range 23-50 days). A patient with reticular dysgenesis failed to engraft following her first transplant, but fully engrafted after a second unrelat ed donor cord blood transplantation. Five of six patients exhibited grade I graft-versus-host disease (GvHD). while one child had grade IV shin and gu t GvHD. Immunologic reconstitution demonstrated that cord blood stem cell t ransplantation resulted in consistent and stable T-, B- and natural killer (NK) cell development. The kinetics of development were such that T-cell de velopment occurred between 60 to 100 days. Initial T-cell engraftment consi sted predominantly of CD45RO+, CD3+, and CD3+ T cells, and at 12 to 24 mont hs changed to CD45RA+, CD3+, and CD4+ T cells, indicating de novo maturatio n of T cells. NK cell development occurred at approximately 180 days. B cel ls engrafted early, and study of functional B-cell antibody responses revea led that five of six patients in whom intravenous immune globulin has been discontinued have low detectable antibody responses to tetanus and diphther ia toroid immunizations 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 disor ders when a suitable HLA-matched donor is not available and when a T-deplet ed haploidentical preparation is not beneficial. Benefits of UCB include ra pid and reliable recovery of immune function, low risk of GvHD, and low vir al transmission rate.