title: Cytoreductive conditioning for severe combined immunodeficiency--help or hindrance?
abstract: Use of chemotherapy-based conditioning-facilitated engraftment in patients with severe combined immunodeficiency (SCID) is contentious. In T- and NK lymphocyte-negative, B-lymphocyte-positive (T-B+NK+) and T-B-NK+ SCID, the osteo-medullary space is occupied by recipient hematopoietic stem cells and mature B-lymphocytes. The thymic niche is empty in T-B+NK+ SCID but fully occupied by developmentally arrested T-lymphocyte precursors in T-B-NK+ SCID. The outcome of infusion of donor stem cells differs and is dependent on genetic defect and the lymphocyte developmental arrest stage. At best, donor hematopoietic stem cell osteo-medullary engraftment induces normal B-lymphocyte function and long-term thymopoiesis; at worst, peripheral expansion of donor T-lymphocytes from the stem cell source results in a restricted T-lymphocyte receptor repertoire with possible B-lymphocyte failure. Conditioning improves immunoreconstitution but causes short- and long-term toxicities, and increased mortality. Newborn screening for SCID will propel the search for safe, effective methods of achieving donor cell engraftment and full immunoreconstitution without toxic sequalae.
authors.affiliation: Hematopoietic Stem Cell Transplantation Department, Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Laberko
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
mesh_terms: D064591:Allografts; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008212:Lymphocyte Depletion; D011173:Portraits as Topic; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019172:Transplantation Conditioning / Q000379:methods*
keywords: chemotherapy conditioning; hematopoietic stem cell transplantation; severe combined immunodeficiency; thymopoiesis