Hematopoietic Stem Cell Transplantation for C1q deficiency: a study on behalf of the EBMT Inborn Errors Working Party

C1q deficiency is a rare inborn error of immunity characterized by an increased susceptibility to infections and development of a wide range of autoimmune manifestations, mimicking SLE, with possible evolution towards a life-threatening condition. Considering that C1q is synthesized by monocytes, four patients have been treated by HSCT with a positive outcome in three. We conducted an international retrospective study to review the outcome of HSCT for C1q deficiency. Eighteen patients, of which fourteen previously unreported, from eleven different referral centres, were included. Two patients had two HSCTs, thus 20 HSCTs were performed in total, at a median age of 10 years (range 0.9 - 19). Indications for HSCT were autoimmune manifestations not controlled by ongoing treatments in seventeen, and early development of MALT lymphoma in one patient. Overall survival (OS) was 71% and event-free survival was 47% at two years (considering an event as acute GvHD ≥ grade II, disease recurrence due to loss of chimerism, and death). In eleven patients HSCT led to autoimmune symptom resolution and discontinuation of immunosuppressive treatments (follow-up time range 3-84 months). Four patients died due to transplant-related complications. Patients with a severe phenotype characterized by neurological and/or renal involvement had the worst OS (40% vs 84%; p=0.034). In conclusion, HSCT is a curative option for C1q deficiency, but careful selection of patients with an accurate balance of risk and benefit is warranted.