Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency.
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.
Aydin, SE; Freeman, AF; Al-Herz, W; Al-Mousa, HA; Arnaout, RK; Aydin, RC; Barlogis, V; Belohradsky, BH; Bonfim, C; Bredius, RG; Chu, JI; Ciocarlie, OC; Doğu, F; Gaspar, HB; Geha, RS; Gennery, AR; Hauck, F; Hawwari, A; Hickstein, DD; Hoenig, M; Ikinciogullari, A; Klein, C; Kumar, A; Ifversen, MRS; Matthes, S; Metin, A; Neven, B; Pai, S-Y; Parikh, SH; Picard, C; Renner, ED; Sanal, Ö; Schulz, AS; Schuster, F; Shah, NN; Shereck, EB; Slatter, MA; Su, HC; van Montfrans, J; Woessmann, W; Ziegler, JB; Albert, MH; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the European Society for Primary Immunodeficiencies,
Volume / Issue
Start / End Page
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)