caa a22 4500 475748204 CHVBK 20180406123519.0 cr unu---uuuuu 170329e20001101xx s 000 0 eng 10.1023/A:1026463900925 doi (NATIONALLICENCE)springer-10.1023/A:1026463900925 Umbilical Cord Blood Transplantation in Severe T-Cell Immunodeficiency Disorders: Two-Year Experience [Elektronische Daten] [Alan Knutsen, Donna Wall] 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 severe T-cell immune deficiency. Umbilical cord blood 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 a matched sibling donor was unavailable. From 1/96 through 5/98, eight children received unrelated cord blood stem cell transplantation following a preparative regimen for the treatment of combined immunodeficiency diseases. The patients ranged in age from 2 weeks to 8 years. The cord blood units were 3/6 HLA antigen matches in two children, 4/6 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 (absolute neutrophil count >500/mm3) was 12 days (range 10-15 days) and the average time for platelet engraftment (platelet count >20,000/mm3) was 36 days (range 24-50 days). A patient with reticular dysgenesis failed to engraft following her first transplant, but fully engrafted after a second unrelated donor cord blood transplantation. Five of six patients exhibited grade I graft-versus-host disease (GvHD), while one child had grade IV skin and gut GvHD. Immunologic reconstitution demonstrated that cord blood stem cell transplantation resulted in consistent and stable T-, B- and natural killer (NK) cell development. The kinetics of development were such that T-cell development occurred between 60 to 100 days. Initial T-cell engraftment consisted predominantly of CD45RO+, CD3+, and CD4+ T cells, and at 12 to 24 months changed to CD45RA+, CD3+, and CD4+ T cells, indicatingde novomaturation of T cells. NK cell development occurred at approximately 180 days. B cells engrafted early, and study of functional B-cell antibody responses revealed that five of six patients in whom intravenous immune globulin has been discontinued have low detectable antibody responses to tetanus and diphtheria toxoid 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 disorders when a suitable HLA-matched donor is not available and when a T-depleted haploidentical preparation is not beneficial. Benefits of UCB include rapid and reliable recovery of immune function, low risk of GvHD, and low viral transmission rate. Plenum Publishing Corporation, 2000 Umbilical cord blood transplantation nationallicence severe combined immunodeficiency nationallicence combine immunodeficiency nationallicence graft-versus-host disease nationallicence Knutsen Alan Divisions of Allergy/Immunology, Department of Pediatrics, St. Louis University Health Sciences Center and Cardinal Glennon Children's Hospital, 63110, St. Louis, Missouri aut Wall Donna Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, St. Louis University Health Sciences Center and Cardinal Glennon Children's Hospital, 63110, St. Louis, Missouri aut Journal of Clinical Immunology Kluwer Academic Publishers-Plenum Publishers 20/6(2000-11-01), 466-476 0271-9142 20:6<466 2000 20 10875 https://doi.org/10.1023/A:1026463900925 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1026463900925 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Knutsen Alan Divisions of Allergy/Immunology, Department of Pediatrics, St. Louis University Health Sciences Center and Cardinal Glennon Children's Hospital, 63110, St. Louis, Missouri aut NATIONALLICENCE 700 1- Wall Donna Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, St. Louis University Health Sciences Center and Cardinal Glennon Children's Hospital, 63110, St. Louis, Missouri aut NATIONALLICENCE 773 0- Journal of Clinical Immunology Kluwer Academic Publishers-Plenum Publishers 20/6(2000-11-01), 466-476 0271-9142 20:6<466 2000 20 10875 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer