Abatacept GVHD prophylaxis in unrelated hematopoietic cell transplantation for pediatric bone marrow failure

Author:

Stenger Elizabeth O.1ORCID,Watkins Benjamin1ORCID,Rogowski Kelsey1ORCID,Chiang Kuang-Yueh2,Haight Ann1,Leung Kathryn1ORCID,Qayed Muna1ORCID,Raghunandan Sharmila1ORCID,Suessmuth Yvonne1,Kean Leslie3ORCID,Horan John13ORCID

Affiliation:

1. 1Division of Pediatric Hematology/Oncology, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA

2. 2Division of Pediatric Hematology/Oncology, University of Toronto/The Hospital for Sick Children, Toronto, Canada

3. 3Division of Pediatric Hematology/Oncology, Dana-Farber/Boston Children’s Hospital, Boston, MA

Abstract

Abstract Hematopoietic cell transplantation (HCT) is the only readily available cure for many life-threatening pediatric nonmalignant diseases (NMD), but most patients lack a matched related donor and are at higher risk for graft-versus-host disease (GVHD). Use of abatacept (Aba) 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 Aba added to standard GVHD prophylaxis (cyclosporine and mycophenolate mofetil) in pediatric patients with NMD undergoing URD HCT. In this single-arm, single-center phase 1 trial, 10 patients receiving reduced intensity or nonmyeloablative conditioning underwent URD HCT. Immune reconstitution was assessed longitudinally via flow cytometry and compared to pediatric patients on Aba2. Nine patients successfully engrafted, with 1 primary graft rejection in the setting of inadequate cell dose; secondary graft rejection occurred in 1 patient with concurrent cytomegalovirus viremia. Two deaths occurred, both unrelated to Aba. One patient developed probable posttransplant 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 Aba, and preservation of naïve relative to effector memory CD4+ T cells was seen akin to Aba2. Thus, 4 doses of Aba were deemed tolerable in pediatric patients with NMD following URD HCT, with encouraging preliminary efficacy and supportive immune correlatives in this NMD cohort.

Publisher

American Society of Hematology

Subject

Hematology

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