Abatacept improves posttransplant survival and reduces endothelial injury syndromes in β-thalassemia major.

Iron overload in transfusion-dependent β-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 GVHD prophylaxis. We performed a retrospective review of children with TDT who underwent HSCT at our center. Patients without abatacept served as controls. A total of 64 children underwent HSCT for TDT. Fifty received abatacept and 14 did not. Acute grade 2 to 4 GVHD was lower in the abatacept cohort (0%) compared with the no-abatacept cohort (35%). Incidence of any endothelial injury syndromes (transplant-associated TMA, sinusoidal obstructive syndrome, posterior reversible encephalopathy, and diffuse alveolar hemorrhage) was lower in the abatacept cohort (16%) compared with no abatacept (64%; P = .0009). Day +14 double-stranded DNA (surrogate of NETs) and soluble c5b-9 were lower in the abatacept cohort than the no-abatacept cohort (P = .04 and P < .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) after HSCT. Thalassemia-free survival was 100% in the abatacept cohort and 71% in the no-abatacept cohort. Addition of abatacept to calcineurin inhibitor-based GVHD prophylaxis resulted in excellent thalassemia-free survival and lower endothelial injury syndromes.