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Aydin, Susanne E.; Freeman, Alexandra F.; Al-Herz, Waleed; Al-Mousa, Hamoud A.; Arnaout, Rand K.; Aydin, Roland C.; Barlogis, Vincent; Belohradsky, Bernd H.; Bonfim, Carmem; Bredius, Robbert G.; Chu, Julia I.; Ciocarlie, Oana C.; Dogu, Figen; Gaspar, Hubert B.; Geha, Raif S.; Gennery, Andrew R.; Hauck, Fabian; Hawwari, Abbas; Hickstein, Dennis D.; Hönig, Manfred; Ikinciogullari, Aydan; Klein, Christoph; Kumar, Ashish; Ifversen, Marianne R. S.; Matthes, Susanne; Metin, Ayse; Neven, Benedicte; Pai, Sung-Yun; Parikh, Suhag H.; Picard, Capucine; Renner, Ellen D.; Sanal, Özden; Schulz, Ansgar S.; Schuster, Friedhelm; Shah, Nirali N.; Shereck, Evan B.; Slatter, Mary A.; Su, Helen C.; Montfrans, Joris van; Woessmann, Wilhelm; Ziegler, John B.; Albert, Michael H. (2018): Hematopoietic stem cell transplantation as treatment for patients with DOCK8 deficiency. In: Journal of Allergy and Clinical Immunology
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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 \textless8 years at HSCT survived, compared to 78% of those \textgreater/=8 years (p=0.06). Of 73 patients with chimerism data available, 65 (89%) had \textgreater90% 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.