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Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency.
- Source :
-
The journal of allergy and clinical immunology. In practice [J Allergy Clin Immunol Pract] 2019 Mar; Vol. 7 (3), pp. 848-855. Date of Electronic Publication: 2018 Nov 02. - Publication Year :
- 2019
-
Abstract
- Background: Biallelic variations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency with eczema, recurrent bacterial and viral infections, and malignancy. Natural disease outcome is dismal, but allogeneic hematopoietic stem cell transplantation (HSCT) can cure the disease.<br />Objective: To determine outcome of HSCT for DOCK8 deficiency and define possible outcome variables.<br />Methods: We performed a retrospective study of the results of HSCT in a large international cohort of DOCK8-deficient patients.<br />Results: We identified 81 patients from 22 centers transplanted at a median age of 9.7 years (range, 0.7-27.2 years) between 1995 and 2015. After median follow-up of 26 months (range, 3-135 months), 68 (84%) patients are alive. Severe acute (III-IV) or chronic graft versus host disease occurred in 11% and 10%, respectively. Causes of death were infections (n = 5), graft versus host disease (5), multiorgan failure (2), and preexistent lymphoma (1). Survival after matched related (n = 40) or unrelated (35) HSCT was 89% and 81%, respectively. Reduced-toxicity conditioning based on either treosulfan or reduced-dose busulfan resulted in superior survival compared with fully myeloablative busulfan-based regimens (97% vs 78%; P = .049). Ninety-six percent of patients younger than 8 years at HSCT survived, compared with 78% of those 8 years and older (P = .06). Of the 73 patients with chimerism data available, 65 (89%) had more than 90% donor T-cell chimerism at last follow-up. Not all disease manifestations responded equally well to HSCT: eczema, infections, and mollusca resolved quicker than food allergies or failure to thrive.<br />Conclusions: HSCT is curative in most DOCK8-deficient patients, confirming this approach as the treatment of choice. HSCT using a reduced-toxicity regimen may offer the best chance for survival.<br /> (Copyright © 2018. Published by Elsevier Inc.)
Details
- Language :
- English
- ISSN :
- 2213-2201
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The journal of allergy and clinical immunology. In practice
- Publication Type :
- Academic Journal
- Accession number :
- 30391550
- Full Text :
- https://doi.org/10.1016/j.jaip.2018.10.035