About: Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions

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About: Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions
Creator	Brodszki, Nicholas Dykes, Josefina Toporski, Jacek Truedsson, Lennart Turkiewicz, Dominik
Source	Medline; PMC
abstract	BACKGROUND: 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. Early intervention is a crucial prognostic factor and a HLA-haploidentical parental donor is often available. 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. 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. RESULTS: Our patient was diagnosed with SCID (T-B + NK+ phenotype). 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. Engraftment was rapid with complete donor chimerism and no signs of GvHD. However, at 12 weeks post HSCT, the patient was still T-cell lymphopenic with clinical symptoms of multiple severe viral infections. Consequently, therapeutic DLIs were initiated for enhanced anti-viral immunity. 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. Following the DLI, a prompt increase in CD3 + CD4+ and CD3 + CD8+ counts was observed with a subsequent clearance of viral infections. No acute or chronic GvHD was observed. CONCLUSIONS: Automated 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. 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. We demonstrate the successful use of this approach following TCR-α/β-cell depleted HSCT for the treatment of SCID.
has issue date	2016-01-15(xsd:dateTime)
bibo:doi	10.1186/s13023-016-0385-3
bibo:pmid	26768987
has license	cc-by
sha1sum (hex)	968d0b07b0b65a15cedfd2357e3ba9649742836e
schema:url	https://doi.org/10.1186/s13023-016-0385-3
resource representing a document's title	Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions
has PubMed Central identifier	PMC4714422
has PubMed identifier	26768987
schema:publication	Orphanet J Rare Dis
resource representing a document's body	covid:968d0b07b0b65a15cedfd2357e3ba9649742836e#body_text
is schema:about of	named entity 'T-CELL' named entity 'DEPLETED' named entity 'CD45RO' named entity 'efficient' named entity 'enriched' named entity 'SEVERE COMBINED IMMUNODEFICIENCY' named entity 'AVAILABLE' named entity 'BUT' named entity 'RECOVERY' named entity 'GRAFTS' named entity 'PROVEN' named entity 'PREVENTING' named entity 'PROGNOSTIC FACTOR' named entity 'TREATING' named entity 'T-CELL' named entity 'SUBSEQUENT' named entity 'INFUSIONS' named entity 'APPROACH' named entity 'SEVERE COMBINED IMMUNODEFICIENCY' named entity 'EARLY' named entity 'NOVEL' named entity 'HEMATOPOIETIC STEM CELL TRANSPLANTATION' named entity 'LYMPHOCYTE' named entity 'HAVE' named entity 'HSCT' named entity 'PROTOCOLS' named entity 'INCIDENCE' named entity 'GVHD' named entity 'SCID' named entity 'HERE' named entity 'HAPLOIDENTICAL' named entity 'VIVO' named entity 'CD45RA' named entity 'DONOR' named entity 'DELAY' named entity 'HLA' named entity 'PARENTAL' named entity 'TREATMENT AVAILABLE' named entity 'DISEASE' named entity 'CD45RO' named entity 'DEPLETION' named entity 'ALPHA' named entity 'SEVERE' named entity 'COMBINES' named entity 'HIGH' named entity 'EFFICIENT' named entity 'CURATIVE TREATMENT' named entity 'EARLY INTERVENTION' named entity 'SELECTIVE' named entity 'HAPLOIDENTICAL' named entity 'INFECTIONS' named entity 'DEPLETED' named entity 'VIRAL INFECTIONS' named entity 'MEMORY' named entity 'PRESENT' named entity 'GRAFT' named entity 'DONOR' named entity 'INDUCING' named entity 'RISK OF' named entity 'NOVEL' named entity 'INCREASED RISK' named entity 'ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION' named entity 'CAUSE' named entity 'TREATMENT' named entity 'ENRICHED' named entity 'INCREASES' named entity 'HOST' named entity 'T-CELLS' named entity 'EX VIVO' named entity 'BACKGROUND' named entity 'DONOR LYMPHOCYTE INFUSION' named entity 'IS A' named entity 'SYSTEM' covid:arg/968d0b07b0b65a15cedfd2357e3ba9649742836e named entity 'protocols' named entity 'vivo' named entity 'risk'

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