Giardino S, Volpi S, Lucioni F, Caorsi R, Schneiderman J, Lang A, Khojah A, Kuijpers T, Papadatou I, Paisiou A, Alonso L, Schulz A, Nufar M, Gattorno M, Faraci M.
Preprint from
Research Square
1 February 2022
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.