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      Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation


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          While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) ( P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC.

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

              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. 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 Cyclosporine, used to prevent graft-versus-host disease, was withdrawn early in patients with mixed T-cell chimerism or disease progression.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. 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. Nonmyeloablative allogeneic stem-cell transplantation can induce sustained regression of metastatic renal-cell carcinoma in patients who have had no response to conventional immunotherapy.

                Author and article information

                Bone Marrow Transplant
                Bone Marrow Transplantation
                Nature Publishing Group
                April 2011
                26 July 2010
                : 46
                : 4
                : 573-579
                [1 ]simpleDepartment of Medical Oncology, National Cancer Centre , Singapore, Singapore
                [2 ]simpleDepartment of Clinical Research, Singapore General Hospital , Singapore, Singapore
                [3 ]simpleDepartment of Diagnostic Radiology, National Cancer Centre , Singapore, Singapore
                [4 ]simpleDepartment of Therapeutic Radiology, National Cancer Centre , Singapore, Singapore
                [5 ]simpleClinical Trials and Epidemiological Sciences, National Cancer Centre , Singapore, Singapore
                Author notes
                [* ]simpleDepartment of Medical Oncology, National Cancer Centre , 11 Hospital Drive, Singapore 169610, Singapore. E-mail: hanchongtoh@ 123456gmail.com
                Copyright © 2011 Macmillan Publishers Limited

                This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                : 11 January 2010
                : 05 May 2010
                : 14 May 2010
                Original Article

                nasopharyngeal cancer,nonmyeloablative allotransplant,graft-vs-tumor
                nasopharyngeal cancer, nonmyeloablative allotransplant, graft-vs-tumor


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