Single-Infusion of Donor Early Apoptotic Cells (ApoCell) As Prophylaxis of Graft-Versus-Host Disease in Myeloablative HLA-Matched Allogeneic Bone Marrow Transplantati

Abstract 4176

Because of its potent immunomodulatory effect together with presumably high safety profile, apoptotic cells infusion (ApoCell) was tested in addition to cyclosporine and methotrexate, as prophylaxis of graft-versus-host disease (GVHD) in HLA-matched myeloablative allogeneic bone marrow transplantation (alloBMT) from a related donor. We conducted a phase I//IIa clinical trial where we treated 13 patients (median age, 37 years; range, 20–59 years) with advanced hematologic malignancies (7 patients with ALL, 5 patients with AML (4 patients with MDS that transformed to AML and one patient with AML de novo), and 1 patient with CML that received conventional myeloablation with 35, or 70, or 140, or 210×10⁶ cell/kg of donor ApoCell, on day -1 of transplantation. Ten serious adverse effects were reported with all being not related (seven) or unlikely to be related (3) to ApoCell infusion. Out of hundreds adverse effects, only three were reported as possibly related to ApoCell infusion (with no definite or probable adverse effects). The non-relapse mortality at day 100 and 180 after transplantation was the same, 7.7%. The overall survival at 100 and 180 days after transplantation was 92% and 85%, respectively. The incidences of acute grades II through IV GVHD for all 13 patients and for the two higher doses were 23% and 0% (six patients), respectively. Biomarker ratio levels including tumor necrosis factor receptor I (TNFR1), hepatocyte growth factor (HGF), interleukin 2 receptor alpha (IL-2Ra), and interleukin 7 (IL-7), supported the clinical data. These results suggest that single-infusion high-dose donor early apoptotic cells in HLA-matched myeloablative alloBMT is a safe and potentially effective single-agent prophylaxis of acute GVHD occurring after myeloablative conditioning (clinicaltrials.gov no. NCT00524784).