Early Apoptotic Cells (ApoCell) As Prophylaxis of Graft-Versus-Host Disease in Myeloablative HLA-Matched Allogeneic Bone Marrow Transplantation Is Safe and Effective: 1 Year Follow-up

Apoptotic cells infusion (ApoCell) is a novel cellular therapy that was found to be effective in a variety of mouse models of autoimmune diseases. ApoCell was tested in humans 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 that received conventional myeloablation with 35, or 70, or 140, or 210x10⁶ cell/kg of donor ApoCell, on day -1 of transplantation (Mevorach et al. BBMT 2014).

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. We now report 1 year overall survival rate which was 62% with a non-relapse survival rate of 89% (100% for the two higher cohorts).

These results are in agreement with additional safety observations that included: ten serious adverse effects with all being not related (7) or unlikely to be related (3) to ApoCell infusion, and only three out of hundreds adverse effects, that were reported as possibly related to ApoCell infusion (with no definite or probable adverse effects).

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. GvHD clinical grade was supported by 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).

These results suggest that single-infusion high-dose donor early apoptotic cells in HLA-matched myeloablative alloBMT is a safe and effective prophylaxis for acute GVHD (clinicaltrials.gov no. NCT00524784).