DOCK8 deficiency is a combined immunodeficiency characterized by profound atopy, chronic viral skin disease, recurrent bacterial infections, and malignancy risk. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy. We aimed to evaluate transplant outcomes, graft characteristics, immune reconstitution, and survival in a large genetically confirmed cohort.
We conducted a retrospective analysis of 47 genetically confirmed DOCK8 deficiency patients who underwent HSCT between 2012 and 2025. Data collected included donor type, conditioning regimen, graft versus host disease (GVHD) prophylaxis, survival, lineage-specific short tandem repeat (STR) chimerism, viral reactivation, IgE reduction, and time to intravenous immunoglobulin (IVIG) discontinuation.
Median age at HSCT was 6 years (interquartile range [IQR] 3–10). Donors were matched sibling donor (MSD)/family matched donor (FMD) (n = 37), matched unrelated donor (MUD) (n = 7), haploidentical (n = 2), and cord blood (n = 1). Conditioning was predominantly busulfan-based regimen 66% combined with fludarabine (Bu/Flu) and 21% with cyclophosphamide (Bu/Cy). Antithymocyte globulin (ATG) was used in 55%. GVHD occurred in 12/47 patients (25.5%) and was more frequent with Bu/Cy than Bu/Flu. Overall survival was 91.5% (43/47). Among 43 patients with available STR data, 41 achieved 100% donor lymphoid and myeloid chimerism. IgE levels decreased by a median of 98%. CMV detection decreased from 54% pre-HSCT to 6% post-HSCT, and EBV from 37.5% to 2%. Median time to IVIG discontinuation was 7.7 months (IQR 4.6–11.4).
HSCT achieved consistent full donor engraftment and excellent survival in DOCK8 deficiency. Significant reduction in infectious and atopic manifestations supports HSCT as definitive therapy with durable immune correction.
