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 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 Cyclosporine, used to prevent graft-versus-host disease, was withdrawn early in patients with mixed T-cell chimerism or disease progression.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.
Childs
R
R
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1652, USA. childsr@nih.gov
Chernoff
A
A
Contentin
N
N
Bahceci
E
E
Schrump
D
D
Leitman
S
S
Read
E J
EJ
Tisdale
J
J
Dunbar
C
C
Linehan
W M
WM
Young
N S
NS
Barrett
A J
AJ
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D016207:Cytokines; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010865:Pilot Projects; D011336:Probability; D016019:Survival Analysis; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D016207:Cytokines