Hematopoietic Stem Cell Transplantation Outcomes for 11 Patients with Dedicator of Cytokinesis 8 Deficiency

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2016 May 1

PMID 27130861

Citations 22

Authors

Waleed Al-Herz

Julia I Chu

Jet van der Spek

Raj Raghupathy

Michel J Massaad

Sevgi Keles

Catherine M Biggs

Lucinda Cockerton

Janet Chou

Ghassan Dbaibo

Scott A Elisofon

Rima Hanna-Wakim

Heung Bae Kim

Leslie E Lehmann

Douglas R McDonald

Luigi D Notarangelo

Paul Veys

Talal A Chatila

Raif S Geha

H Bobby Gaspar

Sung-Yun Pai

Affiliations

Soon will be listed here.

Abstract

Background: Dedicator of cytokinesis 8 (DOCK8) deficiency can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Reports of outcomes are still limited.

Objective: We sought to analyze the results of HSCT in patients with DOCK8 deficiency and report whether approaches resulting in mixed chimerism result in clinically relevant immune reconstitution.

Methods: We performed a retrospective chart review of 11 patients with DOCK8 deficiency and measured DOCK8 expression and cytokine production.

Results: Of 11 patients, 7 received HSCT from related and 4 from unrelated donors; 9 patients received busulfan-based conditioning regimens. Survival was excellent (10 [91%] of 11 patients alive), including a patient who had undergone liver transplantation. Patients showed significant improvements in the frequency and severity of infections. Although eczema resolved in all, food allergies and high IgE levels persisted in some patients. Lymphopenia, eosinophilia, low numbers of naive CD8(+) T cells and switched memory B cells, and TH1/TH2 cytokine imbalance improved in most patients. Although the 8 matched related or unrelated donor recipients had full donor chimerism, all 3 recipients of mismatched unrelated donor HSCT had high levels of donor T-cell chimerism and low B-cell and myeloid cell chimerism (0% to 46%). Almost all switched memory B cells were of donor origin. All patients, including those with mixed chimerism, mounted robust antibody responses to vaccination.

Conclusion: Allogeneic HSCT ameliorated the infectious and atopic symptoms of patients with DOCK8 deficiency. In patients with mixed chimerism, selective advantage for donor-derived T cells and switched memory B cells promoted restoration of cellular and humoral immunity and protection against opportunistic infection.

Citing Articles

Case report: Advanced age at transplantation and pre-emptive treatment with dupilumab in DOCK8 deficiency.

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Sams L, Wijetilleka S, Ponsford M, Gennery A, Jolles S Curr Opin Allergy Clin Immunol. 2023; 23(6):478-490.

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