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

N Engl J Med. 2000 Sep 14;343(11):750-8. doi: 10.1056/NEJM200009143431101.

Abstract

Background: Since allogeneic stem-cell transplantation can induce curative graft-versus-leukemia reactions in patients with hematologic cancers, we sought to induce analogous graft-versus-tumor effects in patients with metastatic renal-cell carcinoma by means of nonmyeloablative allogeneic peripheral-blood stem-cell transplantation.

Methods: Nineteen consecutive patients with refractory metastatic renal-cell carcinoma who had suitable donors received a preparative regimen of cyclophosphamide and fludarabine, followed by an infusion of a peripheral-blood stem-cell allograft from an HLA-identical sibling or a sibling with a mismatch of a single HLA antigen. Cyclosporine, used to prevent graft-versus-host disease, was withdrawn early in patients with mixed T-cell chimerism or disease progression. Patients with no response received up to three infusions 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 had died of transplantation-related causes, and eight from progressive disease. In 10 patients (53 percent) metastatic disease regressed; 3 had a complete 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 consistent with a graft-versus-tumor effect.

Conclusions: Nonmyeloablative allogeneic stem-cell transplantation can induce sustained regression of metastatic renal-cell carcinoma in patients who have had no response to conventional immunotherapy.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary*
  • Carcinoma, Renal Cell / therapy*
  • Cytokines
  • Female
  • Graft vs Host Disease / mortality
  • Graft vs Tumor Effect
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / mortality
  • Histocompatibility Testing
  • Humans
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Lymphocytes*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Pilot Projects
  • Probability
  • Survival Analysis
  • Transplantation Chimera
  • Transplantation Conditioning / methods*
  • Transplantation Immunology
  • Transplantation, Homologous

Substances

  • Cytokines