Hematopoietic stem cell transplantation as treatment for patients with DOCK8 deficiency

Publication date: Available online 2 November 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Susanne E. Aydin, Alexandra F. Freeman, Waleed Al-Herz, Hamoud A. Al-Mousa, Rand K. Arnaout, Roland C. Aydin, Vincent Barlogis, Bernd H. Belohradsky, Carmem Bonfim, Robbert G. Bredius, Julia I. Chu, Oana C. Ciocarlie, Figen Doğu, Hubert B. Gaspar, Raif S. Geha, Andrew R. Gennery, Fabian Hauck, Abbas Hawwari, Dennis D. Hickstein, Manfred Hoenig

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.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2RwIVgf