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

Orphanet Journal of Rare Diseases
Nicholas BrodszkiJosefina Dykes

Abstract

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. 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 ...Continue Reading

References

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Citations

May 23, 2016·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Giuseppina Li PiraMauro Montanari
Mar 29, 2018·Expert Review of Clinical Immunology·Alexandra Laberko, Andrew R Gennery
Nov 2, 2019·Paediatric Drugs·Willem G van GinkelFrancjan J van Spronsen
Jan 9, 2021·Journal of Immunological Methods·Melanie BremmSabine Huenecke

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Methods Mentioned

BETA
leukapheresis
FACS
genotyping

Software Mentioned

Mutation Identification Pipeline ( MIP )
Scout
CliniMACS

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