Published in: New England Journal of Medicine, vol. 343, no. 11, pp. 750-758 (Sept. 14, 2000):
"Regression of Metastatic Renal-Cell Carcinoma after Non-Myeloablative Allogenic Peripheral-Blood Stem-Cell Transplantation".
Richard Childs, M.D.1,Allen Chernoff, M.D.2, Nathalie Contentin, M.D.1, Erkut Bahceci, M.D.1, David Schrump, M.D.3,Susan Leitman, M.D.4, Elizabeth J. Read, M.D.4, John Tisdale, M.D.5, Cynthia Dunbar, M.D.1,W. Marston Linehan, M.D.2,Neal S. Young, M.D.1, and A. John Barrett, M.D.1
Abstract:
Background:
Methods:
Results:
Conclusions:
Affiliations:
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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 non-myeloablative 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 Cyclosporine, used to prevent graft-versus-host disease, was withdrawn early in patients with mixed T-cell chimerism or disease progression.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 287-831 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: Non-myeloablative allogeneic stem-cell transplantation can induce sustained regression of metastatic renal-cell carcinoma in patients who have had no response to conventional immunotherapy.


Affiliations: From the 1 Hematology Branch, National Heart, Lung, and Blood Institute (R.C., N.C., E.B., C.D., N.S.Y., A.J.B.); the 2 Urologic Oncology Branch (A.C., W.M.L.) and the 3 Surgery Branch (D.S.), Division of Clinical Sciences, National Cancer Institute; the 4 Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center (S.L., E.J.R.), and the 5 Molecular and Clinical Hematology Branch (J.T.), National Institute of Diabetes and Digestive and Kidney Diseases - all at the National Institutes of Health, Bethesda, Md.

Correspondence: Address reprint requests to Dr. Childs at the Hematology Branch, NHLBI/NIH. 10/7C103, 10 Center Drive, M.S.C. 1652, Bethesda, MD 20892-1652, or at: childsr@nih.gov

Other authors were Emmanuel Clave, Ph.D., Diane Epperson, Ph.D., and Virginia Mayo, R.N., Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.


Other References:

1. Editorial, Slavin S, "Cancer Immunotherapy with Alloreactive Lymphocytes", New Eng. J. Med. 343: 802 (Sept. 14, 2000).

2. Frenster JH, "Phytohemagglutinin-Activated Autochthonous Lymphocytes for Systemic Immunotherapy of Human Neoplasms", Annals N. Y. Acad. Sci. 277: 45-51 (1976).

3. Hellstrom I, et al, "CD3-Mediated Activation of Tumor-Reactive Lymphocytes from Patients with Advanced Cancer", Proc. Natl. Acad. Sci. USA, 98: 6783-6788 (2001).

4. Childs RW, "Immunotherapy of Solid Tumors: Nonmyeloablative Allogeneic Stem Cell Transplantation",
Advances in Cancer Treatment Newsletter, Medscape Hematology-Oncology eJournal 5(3), June, 2002.
 


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