Selectively T cell depleted allografts from HLA-matched sibling donors followed by low-dose post transplant immunosuppression to improve transplant outcome in patients with hematological malignancies

We evaluated a photodepletion technique to selectively deplete host-reacting T cells from HLA-matched sibling stem cell transplants with the goal of reducing post transplant immunosuppression to improve anti-malignancy effects post allografting. Donor lymphocytes were stimulated with irradiated expanded recipient T lymphocytes in an ex-vivo mixed lymphocyte reaction (MLR). Alloactivated T cells preferentially retaining the photosensitizer 4, 5-dibromorhodamine 123 (TH9402) were eliminated by exposure to visible light. 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 matched sibling along with 5×10 6 /kg selectively depleted donor T cells. Low-dose cyclosporine was used for post-transplant immunosuppression. Eleven patients survive at a median of 30 months. Probabilities (± SEM) for overall and disease free survival are 39 ± 12% and 30 ± 12% respectively, while grade III-IV acute graft-versus-host disease (GVHD) was 13±7 %. Six patients relapsed, with a relapse probability of 27 ± 10%. These results suggest that selectively photodepleted allografts in matched sibling transplantations followed by low-dose immunosuppression may protect against severe acute GvHD but is associated with delayed immune recovery.