Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants.
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.
Martin
P J
PJ
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Hansen
J A
JA
Torok-Storb
B
B
Durnam
D
D
Przepiorka
D
D
O'Quigley
J
J
Sanders
J
J
Sullivan
K M
KM
Witherspoon
R P
RP
Deeg
H J
HJ
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
D006680:HLA Antigens; D007166:Immunosuppressive Agents