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Cytoreductive conditioning for severe combined immunodeficiency - help or hindrance?

Lookup NU author(s): Professor Andrew GenneryORCiD

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Abstract

Use of chemotherapy-based conditioning-facilitated engraftment in patients with severe combined immunodeficiency (SCID) is contentious. In T- and NK lymphocyte-negative, B-lymphocyte-positive (T-B+NK+) and T-B-NK+ SCID, the osteo-medullary space is occupied by recipient hematopoietic stem cells and mature B-lymphocytes. The thymic niche is empty in T-B+NK+ SCID but fully occupied by developmentally arrested T- lymphocyte precursors in T-B-NK+ SCID. The outcome of infusion of donor stem cells differs and is dependent on genetic defect and the lymphocyte developmental arrest stage. At best, donor hematopoietic stem cell osteo-medullary engraftment induces normal B-lymphocyte function and long-term thymopoiesis; at worst, peripheral expansion of donor T- lymphocytes from the stem cell source results in a restricted T- lymphocyte receptor repertoire with possible B-lymphocyte failure. Conditioning improves immunoreconstitution but causes short- and long-term toxicities, and increased mortality. Newborn screening for SCID will propel the search for safe, effective methods of achieving donor cell engraftment and full immunoreconstitution without toxic sequalae.

Publication metadata

Author(s): Laberko A, Gennery AR

Publication type: Editorial

Publication status: Published

Journal: Expert Review of Clinical Immunology

Year: 2015

Volume: 11

Issue: 7

Pages: 785-788

Print publication date: 01/07/2015

Online publication date: 22/06/2015

Acceptance date: 01/01/1900

ISSN (print): 1744-666X

ISSN (electronic): 1744-8409

Publisher: Taylor & Francis

URL: http://dx.doi.org/10.1586/1744666X.2015.1041926

DOI: 10.1586/1744666X.2015.1041926

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