Impact of Abatacept Inclusive Graft-Versus-Host Disease Prophylaxis in Pediatric Stem Cell Transplantation for Hemoglobinopathy

Allogeneic hematopoietic cell transplantation (HCT) provides a curative option for patients with hemoglobinopathies by establishing donor-derived hematopoiesis. However, outcomes are compromised by toxicities and graft-versus-host disease (GVHD), particularly in patients older than 13 years undergoing HCT from unrelated donors. To evaluate the safety and benefit of extended duration (until day +365) abatacept incorporated into GVHD prophylaxis compared to standard prophylaxis that included prednisone in children and adolescents with hemoglobinopathy undergoing HCT from related and unrelated donors. Forty patients with hemoglobinopathy received reduced intensity conditioning and prednisone-inclusive GVHD prophylaxis. Donors were matched siblings or matched/mismatched unrelated donors. Outcomes were compared with 20 subsequent patients who received extended duration abatacept instead of prednisone and targeted lower tacrolimus levels. The incidence of posterior reversible encephalopathy syndrome (PRES) was 17% with prednisone and 0% with abatacept. Acute grade 3 to 4 GVHD occurred in 28% of patients who received prednisone and in 0% that received abatacept (P = .011). Among patients who received prednisone, chronic GVHD (cGVHD) was observed in 2.5% (mild), 5% (moderate), and 30% (severe) of cases. In contrast, abatacept recipients experienced cGVHD at rates of 25% (mild), 5% (moderate), and 5% (severe). Skin/oral involvement was most common in patients with cGVHD who received abatacept. Post-transplant immune reconstitution patterns were similar in both groups. Infection in the presence of GVHD and systemic immune suppression intensification was the primary cause of mortality in patients who received prednisone. The only death in the abatacept group was a patient with primary graft rejection that died after a subsequent transplant. Two patients in the abatacept group developed EBV-associated lymphadenopathy that responded to rituximab. Overall survival and event-free survival were 87% and 80% with prednisone. The corresponding numbers were 95% and 90%, respectively, with abatacept, despite a higher proportion of recipients at risk for poor outcomes (older age, mismatched grafts) in the abatacept group. Including extended duration abatacept and eliminating prednisone as GVHD prophylaxis was safe, effective in eliminating PRES, and reducing the incidence and severity of acute and cGVHD in children, yielding similar outcomes after matched sibling and unrelated donor HCT.