Single Infusion of Donor Mononuclear Early Apoptotic Cells as Prophylaxis for Graft-versus-Host Disease in Myeloablative HLA-Matched Allogeneic Bone Marrow Transplantation: A Phase I/IIa Clinical Trial

Dror Mevorach*, Tsila Zuckerman, Inna Reiner, Avichai Shimoni, Simcha Samuel, Arnon Nagler, Jacob M. Rowe, Reuven Or

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Because of its potent immunomodulatory effect, an infusion of donor mononuclear early apoptotic cells (ApoCell) was tested in addition to cyclosporine and methotrexate as prophylaxis for acute graft-versus-host disease (GVHD) after HLA-matched myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor. In a phase I/IIa clinical trial, we treated 13 patients (median age, 37years; range, 20 to 59years) with hematologic malignancies: 7 patients with acute lymphoblastic leukemia, 5 patients with acute myeloid leukemia, and 1 patient with chronic myeloid leukemia, who received conventional myeloablative conditioning, with 35, 70, 140, or 210×106 cell/kg of donor ApoCell, on day -1 of transplantation. Engraftment was successful in all patients with median time to neutrophil recovery of 13days (range, 11 to 19), and platelet recovery of 15days (range, 11 to 59). Serious adverse effects were reported on 10 occasions in the trial, all of which were considered unrelated (n=7) or unlikely to be related (n=3) to ApoCell infusion. The nonrelapse mortality at day 100 and 180 after transplantation was 7.7% and the overall survival at 100 and 180days after transplantation was 92% and 85%, respectively. All ApoCell preparations showed an invitro significant tolerogenic effect upon interaction with dendritic cells. The overall incidence of acute grades II to IV GVHD was 23%, whereas among those receiving the 2 higher doses (n=6), the rate was 0%. These results suggest that a single infusion of donor ApoCell in HLA-matched allogeneic HSCT is a safe and potentially effective prophylaxis for acute GVHD occurring after myeloablative conditioning. No dose limiting toxicity was observed. (Clinicaltrials.gov no. NCT00524784).

Original languageEnglish
Pages (from-to)58-65
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume20
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Funding

FundersFunder number
Enlivex Therapeutics, Ltd.
Office of the Chief Scientist, Ministry of Economy

    Keywords

    • Apoptotic cells
    • Bone marrow transplantation
    • Graft-versus-host disease

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