HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ARPC1B DEFICIENCY

Abstract Mutations in the component isoform ARPC1B of Human actin-related protein 2/3 complex have been recently associated with combined immunodeficiency related to impaired T-cell function, allergies, autoinflammation, and platelets abnormalities. Currently, indications on the management of this novel disease and information on its outcome are lacking. We report the first case series of 7 children who underwent allogeneic-HSCT (allo-HSCT) with homozygous mutation in ARPC1B gene.All patients presented an early clinical onset, complicated with neonatal hemorrhagic enteritis in 3 and macrophage activating syndrome in 2, characterized by recurrent infections, failure to thrive and gastrointestinal bleeding episodes. Allo-HSCT was performed at the median age of 3.54 years after a myeloablative conditioning regimen in all cases. Engraftment occurred in all patients with a full donor chimerism in 6 out of 7. The clinical course after engraftment was uneventful in 3 out of 7 children; two developed a grade 1-2 acute Graft-versus-Host Disease (GvHD), 1 of them a grade 1 chronic-GvHD. Progressive multifocal leukoencephalopathy JC virus-related was diagnosed in one patient 13 months after haploidentical-HSCT, successfully managed with donor-derived viral-specific T-cell infusion. Only one patient had a severe outcome with veno-occlusive disease and transplant-associated microangiopathy and died 3 months after HSCT because of a sepsis. At a median follow-up of 19 months (range 3 – 110), 6 out of 7 patients are alive and disease free.The severe clinical phenotype at diagnosis and the high survival rate with limited transplant-related morbidity reported strongly support the indication to allo-HSCT for patients with this diagnosis.