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J Allergy Clin Immunol. 2016 Sep;138(3):852-859.e3. doi: 10.1016/j.jaci.2016.02.022. Epub 2016 Apr 6.

Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency.

Author information

1
Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait; Department of Pediatrics, Al-Sabah Hospital, Kuwait City, Kuwait.
2
Division of Hematology-Oncology, Boston Children's Hospital, Boston, Mass; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass.
3
Division of Hematology-Oncology, Boston Children's Hospital, Boston, Mass.
4
Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
5
Division of Immunology, Boston Children's Hospital, Boston, Mass.
6
Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom.
7
Division of Pediatric Infectious Diseases, American University of Beirut, Beirut, Lebanon.
8
Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Mass.
9
Department of Surgery, Boston Children's Hospital, Boston, Mass.
10
Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom; UCL Institute of Child Health, London, United Kingdom.
11
Division of Hematology-Oncology, Boston Children's Hospital, Boston, Mass; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass. Electronic address: sung-yun.pai@childrens.harvard.edu.

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.

KEYWORDS:

Primary immunodeficiency; conditioning; dedicator of cytokinesis 8 deficiency; hematopoietic stem cell transplantation; mixed chimerism

PMID:
27130861
PMCID:
PMC5354354
DOI:
10.1016/j.jaci.2016.02.022
[Indexed for MEDLINE]
Free PMC Article

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