T-Cell Depletion in Unrelated Donor Marrow Transplantation (TCD) Trial

Objectives:

To evaluate the impact of ex vivo T-Cell Depletion of marrow as compared with unmodified grafts on disease-free survival in recipients of unrelated donor bone marrow transplants.

Background:

Chronic graft-versus-host disease (cGVHD) is a major complication and a leading cause of post hematopoietic stem cell transplantion morbidity and mortality. Animal studies suggest that cGVHD is mediated by mature donor T cells that react against disparate recipient histocompatibility antigens. T cell-depletion of donor marrow before infusion into the recipient may ameliorate or prevent GvHD. Unfortunately, since donor T cells also play a key role in mediating graft-versus-tumor (GVT) effects, aggresive GVHD prevention strategies in patients with malignant disease may compromise beneficial antineoplastic GVT effects.

Subjects:

410 patients with hemotologic malignancies were randomized at 15 participating transplantation centers, 203 patients were randomized to receive t-cell-depleted marrow and cyclosporine (TCD arm) and 207 to receive methotrexate and cyclosporine after transplantation of t-cell-replete marrow.

Conclusions:

In spite of a significant reduction of acute GHVD, TCD did not reduce the incidence of cGVHD or improve survival in patients who developed cGVHD. (Blood. 2005; 106(9):3308-3313)