Long Term Follow-Up Of Abatacept, Post-Transplantation Cyclophosphamide and Sirolimus (AbaCyS) based Haploidentical Transplantation in Younger Patients with Nonmalignant Diseases

Background Haploidentical (Haplo) HCT for nonmalignant diseases (NMD) faces inherent challenges of both alloreactivity and graft failure. Building upon promising results from pilot studies, where abatacept was combined with post-transplantation cyclophosphamide (PTCy) and sirolimus (AbaCyS) in younger NMD patients undergoing haplo-HCT, we present the long-term outcomes of this protocol. Study Design On the back of uniform disease-specific conditioning regimens containing ATG (4.5 mg/kg) from day-9 to -7, GVHD prophylaxis (AbaCyS) consisted of abatacept administered on days 0, +5, +20, +35, and monthly until 180 days with PTCy and sirolimus. The patients were followed up with longitudinal assessment of immune reconstitution, growth and reproductive development and quality of life (QoL) analysis. Results Amongst 40 patients (aplastic anemia-24, hemoglobinopathies-14, and primary immunodeficiencies-2) with a median age of 10 years (range, 2-25), 95% achieved sustained engraftment. Post-transplant Hemophagocytic Syndrome was detected in 3 patients, leading to graft failure in 2 cases. The incidence of aGVHD was 2.6%, while that of cGVHD was 14.3%. CMV, adenovirus and EBV infections were observed in 45%, 5% and 0% respectively. Non-relapse mortality, overall survival, EFS and GEFS rates were 5%, 95% 90% and 82%, respectively at a median follow-up of 4.6 years. Absence of cGVHD correlated with younger patient age and early sustained recovery of Tregs and mature NK cells, which in turn was associated with improved QoL and lack of late infections. Conclusions AbaCyS protocol is associated with excellent long-term survival with attenuation of both early and late alloreactivity in over 80% of younger patients undergoing Haplo-HCT for NMD. The study sheds light on predispositions to cGVHD and its impact on QoL, warranting further optimization of this approach.