Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: a review of the literature
Abstract
The nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) family of transcription factors plays an instrumental role in human immunity and lymphoid organ development. Inherited defects affecting these factors or their regulation are associated with increased susceptibility to infections, as well as non-immune abnormalities. Hematopoietic stem cell transplantations (HSCT) have been shown to correct the immune abnormalities in a few patients with NFκB pathway defects. Here we review the pre-HSCT characteristics, as well as the HSCT and outcome of 35 patients who received HSCT for NFκB defects. Twenty-three patients (65.7%) were reported to have survived HSCT. Survival was higher among patients with X-linked ectodermal dysplasia and immunodeficiency (XL-EDA-ID), and those with CARD11-BCL10-MALT1 (CBM) complex defects, in comparison to patients with autosomal dominant ectodermal dysplasia and immunodeficiency (AD-EDA-ID) and IKBKB defects. Survival following myeloablative conditioning was similar to that after reduced intensity conditioning, although donor cells engraftment and immune reconstitution after HSCT was not complete in some patients. The effects of HSCT on organ dysfunction associated with NFκB defects, such as liver toxicity or bowel inflammation, are still not clear. Earlier identification and transplantation of affected patients, as well as better understanding of the pathogenesis and complications of the different NFκB mutations, might improve outcome of HSCT for specific patient populations.
Statement of novelty: This review highlights the current indications, regimens, and outcome of HSCT for inherited defects involving various components of the canonical and non-canonical NFκB pathways.
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Published In
LymphoSign Journal
Volume 4 • Number 2 • June 2017
Pages: 45 - 62
History
Received: 24 December 2016
Accepted: 12 February 2017
Accepted manuscript online: 20 March 2017
Version of record online: 20 March 2017
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© 2017.
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Funding Information
This work was supported in part by the Donald and Audrey Campbell Chair for Immunology research to EG.
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OriScott and EyalGrunebaum. 2017. Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: a review of the literature. LymphoSign Journal.
4(2): 45-62. https://doi.org/10.14785/lymphosign-2016-0016
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