Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency

Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology: In Practice
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Cytokinesis
Hematopoietic Stem Cell Transplantation
Busulfan
Chimerism
treosulfan
Eczema
Graft vs Host Disease
Therapeutics
Survival
Failure to Thrive
Food Hypersensitivity
Mollusca
Virus Diseases
Infection
Bacterial Infections
Cause of Death
Lymphoma
Retrospective Studies
Tissue Donors
T-Lymphocytes

Keywords

  • Combined immunodeficiency
  • DOCK8 deficiency
  • HSCT

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies (Accepted/In press). Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency. Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2018.10.035

Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency. / Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies.

In: Journal of Allergy and Clinical Immunology: In Practice, 01.01.2018.

Research output: Contribution to journalArticle

Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies 2018, 'Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency', Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2018.10.035
Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies. Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency. Journal of Allergy and Clinical Immunology: In Practice. 2018 Jan 1. https://doi.org/10.1016/j.jaip.2018.10.035
Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies. / Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency. In: Journal of Allergy and Clinical Immunology: In Practice. 2018.
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title = "Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency",
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.",
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TY - JOUR

T1 - Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency

AU - Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies

AU - Aydin, Susanne E.

AU - Freeman, Alexandra F.

AU - Al-Herz, Waleed

AU - Al-Mousa, Hamoud A.

AU - Arnaout, Rand K.

AU - Aydin, Roland C.

AU - Barlogis, Vincent

AU - Belohradsky, Bernd H.

AU - Bonfim, Carmem

AU - Bredius, Robbert G.

AU - Chu, Julia I.

AU - Ciocarlie, Oana C.

AU - Doğu, Figen

AU - Gaspar, Hubert B.

AU - Geha, Raif S.

AU - Gennery, Andrew R.

AU - Hauck, Fabian

AU - Hawwari, Abbas

AU - Hickstein, Dennis D.

AU - Hoenig, Manfred

AU - Ikinciogullari, Aydan

AU - Klein, Christoph

AU - Kumar, Ashish

AU - Ifversen, Marianne R.S.

AU - Matthes, Susanne

AU - Metin, Ayse

AU - Neven, Benedicte

AU - Pai, Sung Yun

AU - Parikh, Suhag H.

AU - Picard, Capucine

AU - Renner, Ellen D.

AU - Sanal, Özden

AU - Schulz, Ansgar S.

AU - Schuster, Friedhelm

AU - Shah, Nirali N.

AU - Shereck, Evan

AU - Slatter, Mary A.

AU - Su, Helen C.

AU - van Montfrans, Joris

AU - Woessmann, Wilhelm

AU - Ziegler, John B.

AU - Albert, Michael H.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Combined immunodeficiency

KW - DOCK8 deficiency

KW - HSCT

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