Bone Marrow Transplantation in Severe Combined Immunodeficiency from a Sibling Who Had Received a Paternal Bone Marrow Transplant

Serial transplantation of mismatched donor hematopoietic cells between HLA-identical sibling pairs with congenital immunodeficiency: in vivo tolerance permits rapid immune reconstitution following T-replete transplantation without GVHD in the secondary recipient

“…Potential mechanisms of tolerance include deletion of alloreactive T cells in the thymus of the primary recipient and/or the transfer of peripheral T-regulatory cells with the secondary graft. Successful serial BMT has been described previously, 4 where the recipient of a haploidentical transplant for SCID acted as a donor for his/her unconditioned affected sibling, who received cyclosporin as GVHD prophylaxis. No comparison of immune reconstitution was made in that paper.…”

Hematopoietic stem cell transplantation for primary immunodeficiency disease

“…3,5,9 It is unclear, however, whether a true stem cell graft occurs in the recipient marrow when ablative conditioning is not used, as B cells, myeloid cells and erythroid cells generally remain of recipient origin. 3,5,8,22,23 Host myeloid chimerism has been associated with defective sustained thymopoiesis, except for patients with ILgc deficiency. 8 As with ILgc deficiency, in patients with JAK3 deficiency, HSCT without conditioning successfully reconstitutes T-cell immunity, but rarely accomplishes restoration of NK cell function, and does not produce donor B cells.…”

“…26 At least two studies have identified donor stem cells in the marrow of recipients of unconditioned haplocompatible transplants. 23,27 In one, a sibling was diagnosed with SCID and was HLA matched with her sister who had previously undergone a successful haplocompatible transplant from their father. The sibling received a bone marrow transplant from the older sister and successfully engrafted without any conditioning being given.…”

“…Donor cells were shown to contain stem cells from the father at the time of the second transplant. 23 It has been argued that SCID phenotypes with preservation of NK cells, which have been shown to mediate graft rejection in murine models, would benefit from conditioning regimens that are designed to inhibit NK activity. 4 Grunebaum et al 14 was not able to detect a difference in outcome based on B-cell phenotypes, possibly due to a high use of unrelated donors, for whom busulfan and cyclophosphamide was utilized.…”

“…3,5,20,22 Others perform 'booster' transplants without conditioning with reported improvement in immune function. 5,23 While HSCT may correct some or all of the immunologic abnormalities in patients with SCID, it should be noted that nonimmunologic abnormalities, such as dwarfism and hypoplastic hair in cartilage-hair hypoplasia or neurologic abnormalities in ADA deficiency, 22 may persist. Radiosensitive forms of SCID may be at increased risk of other abnormalities, such as failure of secondary tooth development.…”