Graft-versus-tumor effect against advanced pancreatic cancer after allogeneic reduced-intensity stem cell transplantation

被引:28
作者
Kanda, Y
Komatsu, Y
Akahane, M
Kojima, S
Asano-Mori, Y
Tada, M
Oshima, K
Isayama, H
Ogawa, S
Motokura, T
Chiba, S
Ohtomo, K
Omata, M
Hirai, H
机构
[1] Univ Tokyo, Dept Cell Therapy & Transplantat Med, Bunkyo Ku, Tokyo 1138655, Japan
[2] Univ Tokyo, Dept Gastroenterol, Tokyo, Japan
[3] Univ Tokyo, Dept Radiol, Tokyo, Japan
[4] BML Inc, R&D Ctr, Kawagoe, Saitama, Japan
关键词
reduced-intensity stem cell transplantation; minitransplantation; pancreatic cancer; graft-versus-tumor effect; graft-versus-host disease;
D O I
10.1097/01.TP.0000153507.94980.A5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. The prognosis of advanced pancreatic cancer is extremely poor and therefore a novel treatment strategy is desired. The authors thus started a prospective study of allogeneic reduced-intensity hematopoietic stem cell transplantation (RIST) for patients with advanced pancreatic cancer to evaluate the feasibility and efficacy of this approach for such patients. Methods. Only patients with pathologically proven pancreatic cancer that was locally advanced or metastatic and not amenable to curative resection were included. The conditioning regimen consisted of gemcitabine, fludarabine, and busulfan. Results. In the first stage of this study, the authors treated seven patients. Treatment-related mortality before day 100 was observed in one patient. The median survival after RIST was 229 days. An objective response on computed tomographic scan was observed in two patients and another had a tumor marker response. Marked tumor shrinkage was observed in one of the remaining patients after donor lymphocyte infusion. These antitumor effects appeared after the effect of the conditioning regimen had disappeared. In addition, some of these responses were associated with an increase in the serum anticarcinoembryonic antigen antibody level. Conclusions. Pancreatic cancer appeared to be sensitive to a graft-versus-tumor effect; therefore, a larger clinical study with a refined strategy is warranted.
引用
收藏
页码:821 / 827
页数:7
相关论文
共 32 条
[1]  
Albanopoulos K, 2000, AM J GASTROENTEROL, V95, P1056
[2]  
AOKI K, 1994, JPN J CLIN ONCOL, V24, P85
[3]   Ovarian cancer - Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients [J].
Bay, JO ;
Fleury, J ;
Choufi, B ;
Tournilhac, O ;
Vincent, C ;
Bailly, C ;
Dauplat, J ;
Viens, P ;
Faucher, C ;
Blaise, D .
BONE MARROW TRANSPLANTATION, 2002, 30 (02) :95-102
[4]   REGIMEN-RELATED TOXICITY IN PATIENTS UNDERGOING BONE-MARROW TRANSPLANTATION [J].
BEARMAN, SI ;
APPELBAUM, FR ;
BUCKNER, CD ;
PETERSEN, FB ;
FISHER, LD ;
CLIFT, RA ;
THOMAS, ED .
JOURNAL OF CLINICAL ONCOLOGY, 1988, 6 (10) :1562-1568
[5]   Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors [J].
Blaise, D ;
Bay, JO ;
Faucher, C ;
Michallet, M ;
Boiron, JM ;
Choufi, B ;
Cahn, JY ;
Gratecos, N ;
Sotto, JJ ;
François, S ;
Fleury, J ;
Mohty, M ;
Chabannon, C ;
Bilger, K ;
Gravis, G ;
Viret, F ;
Braud, AC ;
Bardou, VJ ;
Maraninchi, D ;
Viens, P .
BLOOD, 2004, 103 (02) :435-441
[6]   Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer [J].
Bregni, M ;
Dodero, A ;
Peccatori, J ;
Pescarollo, A ;
Bernardi, M ;
Sassi, I ;
Voena, C ;
Zaniboni, A ;
Bordignon, C ;
Corradini, P .
BLOOD, 2002, 99 (11) :4234-4236
[7]   Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial [J].
Burris, HA ;
Moore, MJ ;
Andersen, J ;
Green, MR ;
Rothenberg, ML ;
Madiano, MR ;
Cripps, MC ;
Portenoy, RK ;
Storniolo, AM ;
Tarassoff, P ;
Nelson, R ;
Dorr, FA ;
Stephens, CD ;
VanHoff, DD .
JOURNAL OF CLINICAL ONCOLOGY, 1997, 15 (06) :2403-2413
[8]   Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: Full donor T-cell chimerism precedes alloimmune responses [J].
Childs, R ;
Clave, E ;
Contentin, N ;
Jayasekera, D ;
Hensel, N ;
Leitman, S ;
Read, EJ ;
Carter, C ;
Bahceci, E ;
Young, NS ;
Barrett, AJ .
BLOOD, 1999, 94 (09) :3234-3241
[9]  
Childs R, 2002, BLOOD, V100, p429A
[10]   Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation [J].
Childs, R ;
Chernoff, A ;
Contentin, N ;
Bahceci, E ;
Schrump, D ;
Leitman, S ;
Read, EJ ;
Tisdale, J ;
Dunbar, C ;
Linehan, WM ;
Young, NS ;
Barrett, AJ ;
Clave, E ;
Epperson, D ;
Mayo, V .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (11) :750-758