Single-center analysis of long-term outcome after hematopoietic cell transplantation in children with congenital severe T cell immunodeficiency

Abstract

We review clinical outcome and immune reconstitution in a consecutive series of 74 infants with severe T cell immunodeficiency who received hematopoietic cell transplantation (HCT) from January 1991 to May 2003. Fifty-three patients (71.6%) are alive. Results were significantly better for recipients of HCT from HLA-matched related donors (100% survival) and unrelated donors (86.4%) than from mismatched related donors (51.6%). A detailed analysis of immune reconstitution and clinical status was performed in 49 surviving patients, most of which have attained robust T and B cell reconstitution and are in very good clinical conditions. No cases of late deaths or of chronic graft-versus-host disease (GvHD) have been observed. However, infections and autoimmunity at >1 year after HCT have been observed in a significant number of patients. Persistence of a low number of circulating naive T cells and long-term requirement for intravenous immunoglobulin were associated with a higher incidence of clinical events.

Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID

“…Our data show a superior efficacy of BMT and GT over PEG-ADA treatment in allowing the development of functional Tregs and in preventing the onset of autoimmunity in ADA Ϫ/Ϫ mice. Nevertheless, it shall be noted that some autoimmune manifestations have also been reported in BMT patients 34,35 as well as in patients treated with hematopoietic stem cell GT. 12 Accurate survey and long-term follow-up will be essential to determine the incidence of autoimmune complications after different treatments.…”

Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy

“…Key findings of milder forms of the disease or in patients undergoing PEG-ADA are complications of immune dysregulations, including autoimmunity and allergic manifestations (7)(8)(9)(10). Recently, autoimmune manifestations have also been reported in patients receiving BMT (11,12) and in patients treated with HSC-GT (3). Although autoimmunity is commonly observed in certain B cell and/or T cell immunodeficiencies, it remains unclear to what extent some tolerance mechanisms might be specifically affected in ADA deficiency (13).…”

TRECing long-term success in SCID

“…1 Marking the same anniversary, several European centers have recently reviewed their experiences regarding long-term survival and T-cell function in SCID recipients. [3][4][5][6][7] These reports complement the SarzottiKelsoe report in demonstrating the broad success of hematopoietic cell transplantation (HCT) in treating SCID immune deficiency; the expansion of the donor pool to include HLAmatched-related, haploidentical-related, and HLA-matched unrelated donors; and the long-term stability of T-cell repopulation in SCID recipients (see table).…”

“…Sarzotti-Kelsoe et al confirm that patients with these forms of SCID were able to sustain long-term thymopoiesis, independent of donor chimerism in non-T populations. 1,[4][5][6] Patients with Rag mutations, while showing donor engraftment in T cells, were less healthy and a lower percentage developed significant TREC frequencies.…”

“…Genome-wide association studies (GWASs) are currently a "topical" genomics technology and have successfully identified common genetic variants associated with the risk of numerous common diseases. But the great majority of variants have had odds ratios less than 1.5, 5 and many thousands of subjects have been required to achieve statistical significance. Although unbiased, GWASs identify genomic regions, not genes themselves, and the findings usually lack biologic context.…”