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

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 Cyclosporine, used to prevent graft-versus-host disease, was withdrawn early in patients with mixed T-cell chimerism or disease progression.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.

• Authors: R Childs, A Chernoff, N Contentin, E Bahceci, D Schrump, S Leitman, E J Read, J Tisdale, C Dunbar, W M Linehan, N S Young, A J Barrett
• Journal: The New England journal of medicine (N Engl J Med) Vol. 343 Issue 11 Pg. 750-8 (Sep 14 2000) ISSN: 0028-4793 [Print] United States
• PMID: 10984562 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Cytokines

Topics

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