Successful bone marrow transplantation with split lymphoid chimerism in DiGeorge syndrome

Abstract

A female infant with DiGeorge syndrome associated with severe T-cell immunodeficiency underwent a successful bone marrow transplantation from her HLA-identical, mixed leukocyte culture-nonreactive brother at 5 months of age. Mature circulating T cells and mitogen-induced proliferative responses were detectable at 10 days posttransplant, and by 8 months post-transplant functional T- and B-cell reconstitution was documented by normal responses to mitogens and normal levels of serum immunoglobulins as well as in vitro and in vivo T-cell reactivity to specific antigens and production of specific antibody to T cell-dependent antigens in vivo. Phytohemagglutinin-induced interleukin-2 production and cell surface interleukin-2 receptor expression improved posttransplant, with normal production values observed by 8 months posttransplant. Histologic examination of appendix and thoracic lymph node obtained 9 and 17 months posttransplant, respectively, revealed near-normal lymphoid architecture, with germinal center formation providing morphologic confirmation of reconstitution. Stable split lymphoid chimerism with T cells of donor origin and B cells remaining recipient in origin was documented by sex chromosome analysis. Two years posttransplant the subject remains free of serious infections. In conclusion, this case indicates that bone marrow transplantation can produce peripheral immunoreconstitution without need for significant thymic influence, most likely by providing a source of postthymic T cells, and that bone marrow transplantation should be considered a therapeutic option in patients with DiGeorge syndrome associated with severe T-cell deficiency.

Complete-type DiGeorge syndrome treated by bone marrow transplantation

“…In the case reported by Goldsobel et al 6 T cells had begun to increase 2 weeks after BMT and the number of CD4 cells increased to 281/ l. Thymic serum factor (TSF) was increased 5 months after BMT. In the case reported by Borzy et al 7 the acquisition of T cell function was similar to the former case. The present case also developed T cell function after the second BMT.…”

“…(3) It is possible that post-thymic precursor cells, which were able to expand in peripheral lymph nodes without contact with the thymus, or long-lived memory T cells were infused from the donor, and that these cells increased by various immunological means. The authors in two former reports 6,7 argued that expansion of post-thymic precursor cells was most likely after BMT for DGS. As far as the increment of TSF after BMT in the case of Goldsobel et al 6 is concerned, however, activation of the hypoplastic thymus by infused mature T cells may be possible.…”

“…He had no acute or chronic GVHD. Now, 7 months post-BMT, FACS 929 Table 2 BMT for DiGeorge syndrome Goldsobel et al 6 Borzy et al 7 …”

“…4 BMT has been attempted for DGS in seven patients 5 and two of these underwent transplantation without any pre-conditioning, with favourable results. 6,7 Here, we report a patient with complete-type DGS treated with BMT who exhibited reconstitution of T cell immunity.…”

Complete DiGeorge Anomaly in the Absence of Neonatal Hypocalcemia and Velofacial and Cardiac Defects

“…9,[23][24][25][26] Immune reconstitution is possible through infusion of peripheral mononuclear cells or bone marrow transplantation (BMT) from a genotypically HLA-identical donor or, more recently, through postnatal thymic tissue transplantation. 22,[27][28][29] We report an unusual case of DG-SCID that presented exclusively as SCID, without neonatal hypocalcemia or velofacial or cardiac abnormalities, at the time of diagnosis. The child presented with a SCID phenotype, but normal lymphocyte counts and immunoglobulin levels were noted at the initial presentation, delaying diagnosis.…”