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Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency

Lookup NU author(s): Dr Andrew Gennery, Dr Mary Slatter

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Abstract

© 2018 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.


Publication metadata

Author(s): Aydin SE, Freeman AF, Al-Herz W, Al-Mousa HA, Arnaout RK, Aydin RC, Barlogis V, Belohradsky BH, Bonfim C, Bredius RG, Chu JI, Ciocarlie OC, Dogu F, Gaspar HB, Geha RS, Gennery AR, Hauck F, Hawwari A, Hickstein DD, Hoenig M, Ikinciogullari A, Klein C, Kumar A, Ifversen MRS, Matthes S, Metin A, Neven B, Pai S-Y, Parikh SH, Picard C, Renner ED, Sanal O, Schulz AS, Schuster F, Shah NN, Shereck EB, Slatter MA, Su HC, van Montfrans J, Woessmann W, Ziegler JB, Albert MH

Publication type: Article

Publication status: Published

Journal: Journal of Allergy and Clinical Immunology: In Practice

Year: 2019

Volume: 7

Issue: 3

Pages: 848-855

Print publication date: 01/03/2019

Online publication date: 02/11/2018

Acceptance date: 22/10/2018

ISSN (print): 2213-2198

ISSN (electronic): 2213-2201

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.jaip.2018.10.035

DOI: 10.1016/j.jaip.2018.10.035


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