Abatacept Improves Post-Transplant Survival and Reduces Endothelial Injury Syndromes in Beta-Thalassemia major Open Access

• Abatacept reduced incidence of endothelial-injury syndromes and improved survival in transfusion dependent beta thalassemia

• Patients receiving abatacept did not experience grade II-IV acute GVHD .

Iron overload in transfusion-dependent beta thalassemia (TDT) generates reactive oxygen species, predisposing to post hematopoietic stem cell transplant (HSCT) endothelial activation. Abatacept prevents acute graft versus host disease (GVHD) by inhibiting CD80/CD86 on T-cells, but CD80 is also expressed on neutrophils. Elevated neutrophil extracellular traps (NETs) at day+14 are associated with thrombotic microangiopathy (TMA) after HSCT, mechanistically linking endothelial activation to complement activation. We wanted to compare post HSCT survival and incidence of endothelial injury syndromes in children with TDT with and without addition of abatacept to standard acuteGVHDprophylaxis. We performed a retrospective review of children with TDT who underwent HSCT at our center. All received intravenous busulfan, fludarabine and thiotepa for conditioning and calcineurin inhibitor-based acute GVHD prophylaxis. Patients without abatacept served as controls. Abatacept was administered intravenously at 10 mg/kg on days -1, +5, +14 and +28 after HSCT. Sixty-four children underwent HSCT for TDT. Fifty received abatacept while 14 did not. No differences were observed between rates of neutrophil or platelet engraftment, rates of bacteremia or viral reactivation. Acute grade II-IV GVHD was lower in the abatacept cohort (0%) compared to no abatacept cohort (35%) p=0.0003. Incidence of any endothelial injury syndromes (TA-TMA, SOS, PRES, DAH) was lower in the abatacept cohort (16%) compared to no abatacept (64%) p=0.0009. Day+14 dsDNA( surrogate of NETs) and sC5b-9 values were lower in the abatacept cohort compared to no abatacept cohort (p=0.04 and p<0.001 respectively). All patients in the abatacept cohort had full donor myeloid chimerism and remained transfusion-independent at a median last follow up of 1915 days (range 266-3464 days) post HSCT. Thalassemia-free survival was 100% in the abatacept cohort and 71% in the no abatacept cohort. Addition of abatacept to calcineurin inhibitor based acute GVHD prophylaxis resulted in excellent thalassemia-free survival and lower endothelial injury syndromes.