Cellular therapy for severe combined immunodeficiency: Transplant options and impact of donor type and graft manipulation on long-term graft function and completeness of immune reconstitution

While the ideal donor of stem cells for an infant with severe combined immunodeficiency (SCID) is an HLA-identical sibling, one of the most important therapeutic advances for this condition over the past two decades has been the development of effective methods to deplete post-thymic T cells from haploidentical parental bone marrow. There is extensive experience now showing that the remaining stem cells will confer immunity on infants with SCID without the necessity for pre-transplant conditioning or post-transplant graft-versus-host disease prophylaxis. T cell function was present as soon as 2 weeks after unfractionated marrow but not until 3-4 months after T cell depleted haploidentical marrow stem cells. A total of 580 transplanted SCID patients were identified by the author in a worldwide survey and 375 (65%) were surviving, including 77 transplanted at the author's institution, of whom 60 (78%) were surviving). One hundred twenty-five SCIDs had received HLA-identical marrow and 105 (84%) were surviving, including 12 of 12 (100%) at the author's institution. Four hundred twenty-one had received haploidentical marrow and 256 (61%) were surviving, including 48/65 or 74% of those performed at the author's institution, and two transplanted in utero elsewhere with T cell-depleted paternal marrow. Experience with matched unrelated adult marrow transplantation in SCID is limited, but 12 of 17 recipients (71%) worldwide were surviving. Two of three SCID infants given cord blood transplants at the author's institution were surviving.

Duke Scholars

Author Rebecca Hatcher Buckley Pediatrics, Allergy and Immunology