Abstract
Allogeneic hematopoietic cell transplantation (HCT) provides a curative option for patients with hemoglobinopathies by establishing donor-derived hematopoiesis. However, outcomes can be compromised by toxicities and graft-versus-host disease (GVHD), particularly in patients older than 13 years.
To evaluate the safety and benefit of extended duration (until day +365) abatacept incorporated into GVHD prophylaxis compared to the inclusion of 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. Outcomes were compared with 20 subsequent patients who received extended duration abatacept instead of prednisone.
The incidence of posterior reversible encephalopathy syndrome was 17% with prednisone and 0% with abatacept. Acute grade 3-4 GVHD occurred in 28% of patients who received prednisone and in 0% that received abatacept (p=0.011). Among patients who received prednisone, chronic GVHD was observed in 2.5% (mild), 5% (moderate), and 30% (severe) of cases. In contrast, abatacept recipients experienced chronic GVHD at rates of 25% (mild), 5% (moderate), and 5% (severe). Oral involvement was most common in patients with chronic GVHD who received abatacept. Post-transplant immune reconstitution patterns were similar in both groups. Infection in the presence of GVHD and systemic immune suppression was the primary cause of mortality in patients who received prednisone. Two patients in the abatacept group developed EBV-associated lymphadenopathy that responded to rituximab. The only death following abatacept-inclusive prophylaxis was in a patient that died after primary graft rejection and a subsequent transplant. Overall survival and event-free survival were 87% and 80% (OS) 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 to GVHD prophylaxis is effective in reducing the incidence and severity of GVHD and allows expansion of donor and transplant options in children and adolescents with hemoglobinopathy, with unrelated donor HCT outcomes matching those after matched sibling donor HCT.