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J Allergy Clin Immunol Pract. 2018 Nov 1. pii: S2213-2198(18)30706-2. doi: 10.1016/j.jaip.2018.10.035. [Epub ahead of print]

Hematopoietic stem cell transplantation as treatment for patients with DOCK8 deficiency.

Author information

1
Dr. von Hauner University Children's Hospital, Ludwig Maximilians Universität, Munich, Germany.
2
NIAID, NIH, Bethesda, MD, United States.
3
Department of Pediatrics, Al-Sabah Hospital, Kuwait, Kuwait.
4
Pediatrics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
5
Department of Medicine, Allergy & Inmmunology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
6
Pediatric hematology, Assistance publique des Hopitaux de Marseille, Marseille, France.
7
DSAI (Deutsche Selbsthilfe Angeborene Immundefekte), Schnaitsee, Germany.
8
Pediatric Blood and Marrow Transplantation Program, Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
9
Pediatric Immunology, LUMC, Leiden, Netherlands.
10
Department of Pediatrics, Stanford University School of Medicine, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, United States.
11
Department of Bone Marrow Transplantation, Great Ormond Street Hospital NHS Trust, London, United Kingdom.
12
Department of Pediatric Immunology & Allergy, Ankara University School of Medicine, Ankara, Turkey.
13
Molecular Immunology Unit, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
14
Immunology, Boston Children's Hospital, Boston, Massachusetts, United States.
15
Institute of Cellular Medicine, University of Newcastle upon Tyne, United Kingdom.
16
King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia.
17
ETI/CCR/NCI, National Insitutes of Health, Bethesda, Maryland, United States.
18
Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
19
BMT/Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
20
Department for Children and Adolescents, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
21
Stem Cell Transplantation, St Anna Children´s Hospital, Vienna, Austria.
22
Pediatric Immunology , Ankara Children's Hematology Oncology Training and Research Hospital, Ankara, Turkey.
23
Department for pediatric immuno-hematology and rheumatology, Necker hospital, Paris, France.
24
Pediatric Blood and Marrow Transplant program, Duke University Medical Center, Durham, NC, United States.
25
Study Center of Primary Immunodeficiency, Necker Children's Hospital, Paris, France.
26
Environmental Medicine, TU Munich, Neuherberg, Germany.
27
Department of Pediatrics, Hacettepe University, Ankara, Turkey.
28
Department of Pediatrics, Düsseldorf University Hospital, Düsseldorf, Germany.
29
Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, United States.
30
Pediatric Hematology/Oncology, Oregon & Health Science University, Portland, OR, United States.
31
Paediatric BMT, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
32
Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, United States.
33
Pediatric Immunology and Infectious Diseases, UMC Utrecht, Utrecht, Netherlands.
34
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
35
Immunology & Infectious Diseases, Sydney Children's Hospital, Randwick, NS, Australia.
36
Dr. von Hauner University Children's Hospital, Ludwig Maximilians Universität, Munich, Germany. Electronic address: malbert@med.lmu.de.

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.

KEYWORDS:

DOCK8 deficiency; HSCT; combined immunodeficiency

PMID:
30391550
DOI:
10.1016/j.jaip.2018.10.035

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