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

• Published in: Blood advances Vol. 7; no. 10; pp. 2196 - 2205
• Main Authors: Stenger, Elizabeth O., Watkins, Benjamin, Rogowski, Kelsey, Chiang, Kuang-Yueh, Haight, Ann, Leung, Kathryn, Qayed, Muna, Raghunandan, Sharmila, Suessmuth, Yvonne, Kean, Leslie, Horan, John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-05-2023; The American Society of Hematology
• Subjects: Abatacept - therapeutic use; Bone Marrow Failure Disorders - etiology; Child; Graft vs Host Disease - etiology; Graft vs Host Disease - pathology; Graft vs Host Disease - prevention & control; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Pancytopenia - etiology; Transplantation; Unrelated Donors
• ISSN: 2473-9529; 2473-9537; 2473-9537
• DOI: 10.1182/bloodadvances.2022008545

•Four doses of Aba can be safely added to standard 2-drug GVHD prophylaxis in URD HCT for pediatric bone marrow failure.•No severe acute or chronic GVHD was seen in pediatric patients with bone marrow failure with Aba-containing prophylaxis after URD HCT.
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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.