Single-center randomized trial of T-reg graft alone vs T-reg graft plus tacrolimus for the prevention of acute GVHD

• DOI: 10.1182/bloodadvances.2023011625
• Publication Date: 2023-12-13T21:23:15Z
• Authors: Cameron S. Bader; Anna Pavlova; Robert Lowsky; Lori S. Muffly; Parveen Shiraz; Sally Arai; Laura J. Johnston; Andrew R. Rezvani; Wen-Kai Weng; David B. Miklos; Matthew J. Frank; John S. Tamaresis; Vaibhav Agrawal; Sushma Bharadwaj; Surbhi Sidana; Judith A. Shizuru; Nathaniel B. Fern...; Amy Putnam; Scott Killian; Bryan J. Xie; Robert S. Negrin; Everett H. Meyer
• Keywords: Center (category theory); Single Center; INT

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies which graft-versus-host disease (GVHD) remains major complication. The use of donor T-regulatory cells (Tregs) to prevent GVHD appears promising, including in our previous evaluation an engineered graft product (T-reg graft) consisting the timed, sequential infusion CD34+ stem and high-purity Tregs followed by conventional T cells. However, whether immunosuppressive prophylaxis can be removed from this protocol unclear. We report results first stage open-label single-center phase 2 study (NCT01660607) investigating T-reg myeloablative HCT HLA-matched 9/10-matched recipients. Twenty-four patients were randomized receive alone (n = 12) or plus single-agent determine was noninferior preventing acute GVHD. All developed full-donor myeloid chimerism. Patients with vs had incidences grade 3 4 58% 8% (P .005) 17% 0% .149), respectively. incidence moderate-to-severe chronic 28% arm .056). Among prophylaxis, CD4+ T-cell-to-Treg ratios reduced after transplantation, gene expression profiles showed proliferation, achievement T-cell chimerism delayed. This indicates that tacrolimus preferred over prevention trial registered at www.clinicaltrials.gov as #NCT01660607.