Abatacept GVHD Prophylaxis in Unrelated Hematopoietic Cell Transplantation for Pediatric Bone Marrow Failure.

Hematopoietic cell transplantation (HCT) is the only readily available cure for many life-threatening pediatric non-malignant diseases (NMD), but most patients lack a matched related donor and are at higher risk for graft-versus-host disease (GVHD). Use of abatacept to target donor T cell activation has been safe and effective in preventing GVHD after unrelated donor (URD) HCT for malignant diseases (Aba2 trial). Our primary objective was to evaluate the tolerability of abatacept added to standard GVHD prophylaxis (cyclosporine and mycophenolate mofetil) in pediatric NMD patients undergoing URD HCT. In this single arm, single center phase 1 trial, 10 patients receiving reduced intensity or non-myeloablative conditioning underwent URD HCT. Immune reconstitution was assessed longitudinally via flow cytometry and compared to pediatric patients on Aba2. Nine patients successfully engrafted, with one primary graft rejection in the setting of inadequate cell dose; secondary graft rejection occurred in one patient with concurrent CMV viremia. Two deaths occurred, both unrelated to abatacept. One patient developed probable post-transplant lymphoproliferative disease, responsive to rituximab and immune suppression withdrawal. No patients developed severe acute or chronic GVHD, and 8 patients were off systemic immunosuppression at 1 year. Immune reconstitution did not appear to be impacted by abatacept, and preservation of naïve relative to effector memory CD4+ T cells was seen akin to Aba2. Thus, four doses of abatacept were deemed tolerable in pediatric NMD patients following URD HCT, with encouraging preliminary efficacy and supportive immune correlatives in this NMD cohort. This clinical trial is registered at clinicaltrials.gov: NCT01917708.