Aydin, SE;
Freeman, AF;
Al-Herz, W;
Al-Mousa, HA;
Arnaout, RK;
Aydin, RC;
Barlogis, V;
... Inborn Errors Working Party of the European Group for Blood and; + view all
(2019)
Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency.
Journal of Allergy and Clinical Immunology: In Practice
, 7
(3)
pp. 848-855.
10.1016/j.jaip.2018.10.035.
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Abstract
BACKGROUND: Biallelic variations in the 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. OBJECTIVE: To determine outcome of HSCT for DOCK8 deficiency and define possible outcome variables. METHODS: We performed a retrospective study of the results of HSCT in a large international cohort of DOCK8 deficient patients. RESULTS: We identified 81 patients from 22 centers transplanted at a median age of 9.7 years (range: 0.7-27.2) between 1995 and 2015. After median follow-up of 26 months (3-135), 68 of 81 patients are alive (84%). Severe acute (III-IV) or chronic graft versus host disease (GVHD) occurred in 11% and 10% respectively. Causes of death wereinfections (n=5), GVHD (5), multi-organ failure (2) and pre-existent 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 to fully myeloablative busulfan-based regimens (97% vs. 78%; p=0.049). 96% of patients aged <8 years at HSCT survived, compared to 78% of those ≥8 years (p=0.06). Of 73 patients with chimerism data available, 65 (89%) had >90% donor T-cell chimerism at last follow-up. Not all disease manifestations responded equally well to HSCT: eczema, infections and Mollusca resolved better than food allergies or failure to thrive. CONCLUSION: 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.
| Type: | Article |
|---|---|
| Title: | Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jaip.2018.10.035 |
| Publisher version: | https://doi.org/10.1016/j.jaip.2018.10.035 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | DOCK8 deficiency, HSCT, combined immunodeficiency |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10062256 |
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