Allogeneic hematopoietic cell transplantation is curative in CARMIL2 deficiency.

Biallelic loss-of-function variants in capping protein regulator and myosin 1 linker 2 (CARMIL2) cause a complex disorder of immune dysregulation hallmarked by susceptibility to infections, inflammatory bowel and skin disease, and Epstein-Barr virus-positive smooth muscle tumors (EBV+ SMTs). We report a multicenter retrospective study to evaluate hematopoietic cell transplantation (HCT) outcomes in CARMIL2-deficient patients. 17 patients underwent 19 HCTs, with a total follow-up of 768 mo and a median follow-up of 37 mo (range 1-195). Three patients died during the early posttransplant period (overall survival, 82.4%), and two required a second HCT for graft failure. Despite limitations due to cohort size and high pre-transplant morbidity in individual patients, HCT improved all major disease manifestations, including infections, inflammatory disease, and previously treatment-refractory EBV+ SMTs. No patient required immunoglobulin replacement after HCT, and no detrimental effects of mixed chimerism were noted. Allogeneic HCT is therefore a curative option for patients with CARMIL2 deficiency, which should be offered upon diagnosis.