title: Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants.
abstract: Results of a previous study suggested that the risk of graft failure 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 fractionated TBI (p less than 0.05, log-rank test). Patients with acute leukemia had a higher risk of graft failure than patients with chronic myelogenous leukemia (p less than 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 suggest that a host factor may have been involved in a presumably 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.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
authors.forename: P J
authors.initials: PJ
authors.lastname: Martin
authors.forename: J A
authors.initials: JA
authors.lastname: Hansen
authors.forename: B
authors.initials: B
authors.lastname: Torok-Storb
authors.forename: D
authors.initials: D
authors.lastname: Durnam
authors.forename: D
authors.initials: D
authors.lastname: Przepiorka
authors.forename: J
authors.initials: J
authors.lastname: O'Quigley
authors.forename: J
authors.initials: J
authors.lastname: Sanders
authors.forename: K M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: R P
authors.initials: RP
authors.lastname: Witherspoon
authors.forename: H J
authors.initials: HJ
authors.lastname: Deeg
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D002986:Clinical Trials as Topic; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008212:Lymphocyte Depletion; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents