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Relationship between patterns of engraftment in peripheral blood and immune reconstitution after allogeneic bone marrow transplantation for (severe) combined immunodeficiency van Leeuwen JE; van Tol MJ; Joosten AM; Schellekens PT; van den Bergh RL; Waaijer JL; Oudeman-Gruber NJ; van der Weijden-Ragas CP; Roos MT; Gerritsen EJ; et al.Blood 1994[Dec]; 84 (11): 3936-47We report the outcome of allogeneic bone marrow transplantation (BMT) as treatment for severe combined immunodeficiency disease (SCID) in 31 patients grafted from 1968 until 1992. The patients received a graft from an HLA-identical related (n = 10), an HLA-haplo-identical related (n = 19), or a closely HLA-matched unrelated (n = 2) donor that resulted in the long-term survival of 6 of 10, 9 of 19, and 0 of 2 children, respectively. Major complications included failure of engraftment and early death caused by respiratory failure. The chimerism pattern and immunologic reconstitution were evaluated in 15 children who survived more than 1 year with sustained engraftment. The pattern of engraftment was investigated within flow-sorted peripheral blood (PB) T- and B-lymphoid, natural killer (NK), and myelomonocytic cell populations using the amplification of variable number of tandem repeats by the polymerase chain reaction. The immunologic reconstitution was assessed by various in vitro and in vivo parameters. Although the number of PB T cells and the in vitro T-cell proliferative response was in the lower region of normal in the majority of cases and even subnormal in some, in all cases donor T-cell engraftment and reconstitution of T-cell immunity was observed. Residual host-type T cells (1% to 5%) were detected in eight cases at multiple occasions. All children showed normal serum IgM and IgG subclass levels and produced specific IgG antibodies after vaccination, irrespective of donor B-cell engraftment. However, three HLA haplo-identical graft recipients with host-type B lymphoid and myeloid cells have a persistent selective IgA deficiency. NK cells were either of donor, host, or mixed origin. Donor NK cell engraftment restored defective in vitro NK cell function of the recipient. We conclude that determination of lineage-specific engraftment patterns provides valuable information for the understanding of the immunologic reconstitution after allogeneic BMT for SCID.|*Graft Survival[MESH]|*Lymphocyte Subsets[MESH]|Antibody Formation[MESH]|Bone Marrow Transplantation/adverse effects/mortality/*pathology[MESH]|Cause of Death[MESH]|Child, Preschool[MESH]|Female[MESH]|Flow Cytometry[MESH]|Graft vs Host Disease/epidemiology[MESH]|Histocompatibility[MESH]|Humans[MESH]|Immunity, Cellular[MESH]|Infant[MESH]|Infant, Newborn[MESH]|Lymphocyte Count[MESH]|Male[MESH]|Minisatellite Repeats[MESH]|Polymerase Chain Reaction[MESH]|Retrospective Studies[MESH]|Severe Combined Immunodeficiency/pathology/*therapy[MESH]|Survival Rate[MESH]|Transplantation, Homologous[MESH]|Treatment Outcome[MESH] |
