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Multicenter Study
. 2019 Mar;7(3):848-855.
doi: 10.1016/j.jaip.2018.10.035. Epub 2018 Nov 2.

Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency

Susanne E Aydin  1 , Alexandra F Freeman  2 , Waleed Al-Herz  3 , Hamoud A Al-Mousa  4 , Rand K Arnaout  5 , Roland C Aydin  1 , Vincent Barlogis  6 , Bernd H Belohradsky  7 , Carmem Bonfim  8 , Robbert G Bredius  9 , Julia I Chu  10 , Oana C Ciocarlie  11 , Figen Doğu  12 , Hubert B Gaspar  13 , Raif S Geha  14 , Andrew R Gennery  15 , Fabian Hauck  1 , Abbas Hawwari  16 , Dennis D Hickstein  17 , Manfred Hoenig  18 , Aydan Ikinciogullari  12 , Christoph Klein  1 , Ashish Kumar  19 , Marianne R S Ifversen  20 , Susanne Matthes  21 , Ayse Metin  22 , Benedicte Neven  23 , Sung-Yun Pai  24 , Suhag H Parikh  25 , Capucine Picard  26 , Ellen D Renner  27 , Özden Sanal  28 , Ansgar S Schulz  18 , Friedhelm Schuster  29 , Nirali N Shah  30 , Evan B Shereck  31 , Mary A Slatter  32 , Helen C Su  33 , Joris van Montfrans  34 , Wilhelm Woessmann  35 , John B Ziegler  36 , Michael H Albert  37 ; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies
Affiliations
Multicenter Study

Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency

Susanne E Aydin et al. J Allergy Clin Immunol Pract. 2019 Mar.

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.

Keywords: Combined immunodeficiency; DOCK8 deficiency; HSCT.

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Conflict of interest statement

Conflicts of interest: The rest of the authors declare that they have no relevant conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
Kaplan-Meier analysis of OS post-HSCT (A) of the entire cohort, (B) by donor type, (C and D) by type of conditioning, (E) by age at HSCT, and (F) by the year of HSCT. RIC, Reduced-intensity conditioning.
FIGURE 2.
FIGURE 2.
Chimerism at last follow-up. Donor chimerism at last follow-up in 73 patients in whom data were available in (A) whole blood and (B) T cells. f/u, Follow-up.
FIGURE 3.
FIGURE 3.
Correction of disease-related symptoms by HSCT. Treating physicians were asked how they rated the correction of symptoms associated with DOCK8 deficiency after HSCT.
See this image and copyright information in PMC

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