TY - JOUR
T1 - Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency
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 B
AU - Slatter, Mary A
AU - Su, Helen C
AU - van Montfrans, Joris
AU - Woessmann, Wilhelm
AU - Ziegler, John B
AU - Albert, Michael H
AU - Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies
N1 - Copyright © 2018. Published by Elsevier Inc.
PY - 2019/3
Y1 - 2019/3
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.
UR - http://www.scopus.com/inward/record.url?scp=85058623217&partnerID=8YFLogxK
U2 - 10.1016/j.jaip.2018.10.035
DO - 10.1016/j.jaip.2018.10.035
M3 - Journal article
C2 - 30391550
SN - 2213-2198
VL - 7
SP - 848
EP - 855
JO - The journal of allergy and clinical immunology. In practice
JF - The journal of allergy and clinical immunology. In practice
IS - 3
ER -