Hematopoietic stem cell transplantation as treatment for patients with DOCK8 deficiency

Aydin, Susanne E.; Freeman, Alexandra F.; Al-Herz, Waleed; Al-Mousa, Hamoud A.; Arnaout, Rand K.; Aydin, Roland; Barlogis, Vincent; Belohradsky, Bernd; Bonfim, Carmem; Bredius, Robbert; Chu, Julia I.; Ciocarlie, Oana; Doğu, Figen; Gaspar, Hubert; Geha, Raif; Gennery, Andrew; Hauck, Fabian; Hawwari, Abbas; Hickstein, Dennis; Hoenig, Manfred

Hematopoietic stem cell transplantation as treatment for patients with DOCK8 deficiency

Basic Data Publication

Publikationstyp

Journal Article

Date Issued

2019-03-01

Sprache

English

TORE-URI

https://hdl.handle.net/11420/41125

Publisher Version

Journal

Journal of Allergy and Clinical Immunology: In Practice

Volume

7

Issue

3

Start Page

1

End Page

17

Citation

Journal of Allergy and Clinical Immunology: In Practice: 7 (3) 1-17 (2019-03-01)

Publisher DOI

10.1016/j.jaip.2018.10.035

Scopus ID

2-s2.0-85058623217

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. 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 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. 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.

Content

Subjects

DOCK8 deficiency

Combined immunodeficiency

HSCT

DDC Class

610: Medicine, Health