Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants
Results of a previous study suggested that the risk of graft failue after transplantation of HLA-identical T cell-depleted marrow may be influenced by the preparative regimen. Subsequent clinical trials were carried out to clarify this relationship and to determine whether post-transplant immunosuppression could have an effect on graft durability. Two factors were found to be associated with graft failure. Patients with hematologic malignancy given a preparative regimen of cyclophosphamide (120 mg/kg) and 15.75 Gy fractionated total body irradiation (TBI) had a 27% cumulative incidence of graft failure, which was less than the 69% incidence seen previously in patients given cyclophosphamide and 12.0 Gy fractioned TBI (p < 0.05, log-rank test). Patients with acute leukemia had a higher risk of graft failure than patients with chronic myelogenous leukemia (p < 0.005). The incidence of graft failure was not influenced by post-transplant immunosuppression with cyclosporine, methotrexate or a combination of cyclosporine plus methotrexate or by the omission of all post-transplant immunosuppression. Similarly, graft failure was not associated with the complement lot used for marrow treatment, the recovery of BFU-E or CFU-GM, or with the number of nucleated cells or T cells in the graft. The effect of primary diagnosis and the inverse relationship between the amount of pretransplant TBI and the graft failure rate suggested that a host factor may have been involved in a presuably immune-mediated rejection. This observation further leads to the inference that certain T cells present in donor marrow can suppress host immunity or help to maintain function of the graft.
Martin, PJ; Hansen, JA; Torok-Storb, B; Durnam, D; Przepiorka, D; O'Quigley, J; Sanders, J; Sullivan, KM; Witherspoon, RP; Deeg, HJ; Appelbaum, FR; Stewart, P; Weiden, P; Doney, K; Buckner, CD; Clift, R; Storb, R; Thomas, ED
Bone Marrow Transplantation
Volume / Issue
Start / End Page