Selectively T Cell Depleted Allografts From HLA-Matched Sibling Donors Followed by Low-Dose Post Transplant Immunosuppression to Limit Disease Relapse In Patients with Hematological Malignancies

Abstract 4705

We evaluated a photodepletion technique to selectively deplete graft-versus-host disease (GVHD) alloreacting T cells from stem cell transplants. Donor lymphocytes were stimulated with irradiated in-vitro expanded recipient T lymphocytes. Alloactivated T cells preferentially retaining the photosensitizer 4, 5-dibromorhodamine 123 (TH9402) (Kiadis Pharma, NL) were eliminated by light exposure. Twenty-four patients with hematological malignancies (16 high-risk) conditioned with fludarabine, cyclophosphamide and total body, irradiation received a CD34-selected stem cell allograft from an HLA identical sibling and 5×10⁶/kg selectively depleted (SD) donor T cells. Low-dose cyclosporine was used as the only post-transplant immunosuppression. The overall probability of grade III-IV a-GVHD was 13%. Fourteen patients developed chronic GVHD (c-GVHD). Five patients relapsed, 2 of whom remain alive in remission after further treatment. Thirteen patients survive at a median of 22 months. Overall survival and disease free survival probabilities (+/− SEM) were 43 +/− 13% and 35 +/− 13% respectively. The SD technique resulted in a low incidence of relapse (24 +/− 10%), but was complicated by late non-relapse mortality associated with c-GVHD and infection of 50 +/− 14% at 4 years follow up. These results suggest that SD may effectively reduce severe a-GVHD while conserving graft-versus leukemia effects, but the depletion strategy has yet to be optimized.