If unrecognized, it can cause death during the first years of life, due to the life-threatening increased susceptibility to infections therefore early detection and treatment of SCID, before infections become overwhelming, optimizes survival. Severe combined immunodeficiency (SCID) is a rare disorder defined by a profound developmental or functional defect of T lymphocytes. We demonstrate the successful use of this approach following TCR-α/β-cell depleted HSCT for the treatment of SCID. In the haploidentical setting, CD45RA+ depleted DLIs can be safely administered at low T-cell doses for efficient enhancement of viral immunity and limited risk of GvHD. ConclusionsĪutomated depletion of CD45RA+ naïve T-cells from unmobilized whole blood is a simple and rapid strategy to provide unmanipulated DLIs, with a potentially broad repertoire of pathogen specific memory T-cells. Following the DLI, a prompt increase in CD3 + CD4+ and CD3 + CD8+ counts was observed with a subsequent clearance of viral infections. The patient was treated with CD45RA+ depleted haploidentical maternal donor lymphocytes enriched from unmobilized whole blood, and a total T-cell dose of no more than 25 x10 3 CD3+ cells/kg with >99.9 % purity of CD3 + CD45RO+ memory T-cells was transferred. Consequently, therapeutic DLIs were initiated for enhanced anti-viral immunity. However, at 12 weeks post HSCT, the patient was still T-cell lymphopenic with clinical symptoms of multiple severe viral infections. Engraftment was rapid with complete donor chimerism and no signs of GvHD. At 9 months of age, he received a T cell receptor(TCR)α/β-cell depleted graft from his haploidentical mother, following a reduced intensity conditioning regimen with no additional GvHD prophylaxis. Our patient was diagnosed with SCID (T-B + NK+ phenotype). Here, we present a novel approach for treating SCID that combines selective depletion of GvHD-inducing alpha/beta (α/β) T-cells from the haploidentical HSCT graft with a subsequent donor lymphocyte infusion (DLI) enriched for CD45RO+ memory T-cells. Haploidentical HSCT protocols utilizing extensively ex vivo T-cell depleted grafts (CliniMACs system) have proven efficient in preventing GvHD, but cause a delay in early T-cell recovery that increases the risk of viral infections. Early intervention is a crucial prognostic factor and a HLA-haploidentical parental donor is often available. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for severe combined immunodeficiency (SCID) although, there is a high incidence of severe infections and an increased risk of graft-versus host-disease (GvHD) with HSCT.
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