Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation

Background: Since allogeneic stem-cell transplantation can induce curative graft-versus-leukemia reactions in patients with hematologic cancers, we so ught to induce analogous graft-versus-tumor effects in patients with metast atic renal-cell carcinoma by means of nonmyeloablative allogeneic periphera l-blood stem-cell transplantation. Methods: Nineteen consecutive patients with refractory metastatic renal-cel l carcinoma who had suitable donors received a preparative regimen of cyclo phosphamide and fludarabine, followed by an infusion of a peripheral-blood stem-cell allograft from an HLA-identical sibling or a sibling with a misma tch of a single HLA antigen. Cyclosporine, used to prevent graft-versus-hos t disease, was withdrawn early in patients with mixed T-cell chimerism or d isease progression. Patients with no response received up to three infusion s of donor lymphocytes. Results: At the time of the last follow-up, 9 of the 19 patients were alive 287 to 831 days after transplantation (median follow-up, 402 days). Two ha d died of transplantation-related causes, and eight from progressive diseas e. In 10 patients (53 percent) metastatic disease regressed; 3 had a comple te response, and 7 had a partial response. The patients who had a complete response remained in remission 27, 25, and 16 months after transplantation. Regression of metastases was delayed, occurring a median of 129 days after transplantation, and often followed the withdrawal of cyclosporine and the establishment of complete donor-T-cell chimerism. These results are consis tent with a graft-versus-tumor effect. Conclusions: Nonmyeloablative allogeneic stem-cell transplantation can indu ce sustained regression of metastatic renal-cell carcinoma in patients who have had no response to conventional immunotherapy. (N Engl J Med 2000;343: 750-8.) (C) 2000, Massachusetts Medical Society.