Aydin, Susanne E.Susanne E.AydinFreeman, Alexandra F.Alexandra F.FreemanAl-Herz, WaleedWaleedAl-HerzAl-Mousa, Hamoud A.Hamoud A.Al-MousaArnaout, Rand K.Rand K.ArnaoutAydin, RolandRolandAydinBarlogis, VincentVincentBarlogisBelohradsky, BerndBerndBelohradskyBonfim, CarmemCarmemBonfimBredius, RobbertRobbertBrediusChu, Julia I.Julia I.ChuCiocarlie, OanaOanaCiocarlieDoğu, FigenFigenDoğuGaspar, HubertHubertGasparGeha, RaifRaifGehaGennery, AndrewAndrewGenneryHauck, FabianFabianHauckHawwari, AbbasAbbasHawwariHickstein, DennisDennisHicksteinHoenig, ManfredManfredHoenigIkinciogullari, AydanAydanIkinciogullariKlein, ChristophChristophKleinKumar, AshishAshishKumarIfversen, MarianneMarianneIfversenMatthes-Martin, SusanneSusanneMatthes-MartinMetin, AyseAyseMetinNeven, BenedicteBenedicteNevenPai, Sung YunSung YunPaiParikh, SuhagSuhagParikhPicard, CapucineCapucinePicardRenner, EllenEllenRennerSanal, ÖzdenÖzdenSanalSchulz, AnsgarAnsgarSchulzSchuster, FriedhelmFriedhelmSchusterShah, NiraliNiraliShahShereck, EvanEvanShereckSlatter, MaryMarySlatterSu, HelenHelenSuvan Montfrans, JorisJorisvan MontfransWoessmann, WilhelmWilhelmWoessmannZiegler, JohnJohnZieglerAlbert, MichaelMichaelAlbert2023-07-112023-07-112019-03-01Journal of Allergy and Clinical Immunology: In Practice: 7 (3) 1-17 (2019-03-01)https://hdl.handle.net/11420/41125Background: 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.en2213-219820193117DOCK8 deficiencyCombined immunodeficiencyHSCTMedicine, HealthJournal Article10.1016/j.jaip.2018.10.035Journal Article