Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency

Aydin, S.E.; Freeman, A.F.; Al-Herz, W.; Al-Mousa, H.A.; Arnaout, R.K.; Aydin, R.C.; Barlogis, V.; Belohradsky, B.H.; Bonfim, C.; Bredius, R.G.; Chu, J.I.; Ciocarlie, O.C.; Dogu, F.; Gaspar, H.B.; Geha, R.S.; Gennery, A.R.; Hauck, F.; Hawwari, A.; Hickstein, D.D.; Hoenig, M.; Ikinciogullari, A.; Klein, C.; Kumar, A.; Ifversen, M.R.S.; Matthes, S.; Metin, A.; Neven, B.; Pai, S.Y.; Parikh, S.H.; Picard, C.; Renner, E.D.; Sanal, O.; Schulz, A.S.; Schuster, F.; Shah, N.N.; Shereck, E.B.; Slatter, M.A.; Su, H.C.; Montfrans, J. van; Woessmann, W.; Ziegler, J.B.; Albert, M.H.; Inborn Errors Working Party Europe; European Soc Primary Immunodefici

doi:doi:10.1016/j.jaip.2018.10.035

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...Show moreBACKGROUND: 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. (C) 2018 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & ImmunologyShow less

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Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency