Document Detail

Cyclophosphamide-using nonmyeloablative allogeneic cell therapy against renal cancer with a reduced risk of graft-versus-host disease.
MedLine Citation:
PMID:  17289899     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Much attention has been paid to nonmyeloablative allogeneic stem cell transplantation for the treatment of renal cancer. We recently proposed a cyclophosphamide-using nonmyeloablative cell therapy in which donor lymphocyte infusion (DLI) was carried out after the tolerance induction to donor cells. In considering the clinical application of the cyclophosphamide-using cell therapy, attempts to reduce graft-versus-host disease (GVHD) are crucial. The aim of the present study was to modify the cyclophosphamide-using cell therapy to reduce the risk of GVHD while preserving the antitumor activity against renal cancer. EXPERIMENTAL DESIGN: We assessed whether a delay in performing DLI from day 1 to day 5 after the cyclophosphamide treatment could reduce the risk of GVHD while preserving antitumor activity against RENCA, a murine carcinogen-induced renal cell carcinoma, in the cyclophosphamide-using cell therapy. RESULTS: Regarding the in vivo antitumor effect, there was no difference between DLI on day 1 and day 5 after the cyclophosphamide treatment, whereas the histologic findings of the small intestine showed that the cyclophosphamide-using cell therapy with DLI on day 5 decreased the risk of GVHD. In addition, the acquired immunity against RENCA was also observed in the RENCA-rejected mice that had been treated with DLI on day 5. CONCLUSIONS: Our results show that a delay in DLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate graft-versus-tumor effects from GVHD by reducing the risk of GVHD.
Masatoshi Eto; Masahiko Harano; Katsunori Tatsugami; Mamoru Harada; Yoriyuki Kamiryo; Keijiro Kiyoshima; Masumitsu Hamaguchi; Masazumi Tsuneyoshi; Yasunobu Yoshikai; Seiji Naito
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  13     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-09     Completed Date:  2007-05-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1029-35     Citation Subset:  IM    
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Antineoplastic Agents / pharmacology
Antineoplastic Agents, Alkylating / pharmacology*
Cell Transplantation / methods
Cyclophosphamide / pharmacology*
Graft vs Host Disease / drug therapy*
Kidney Neoplasms / drug therapy*
Lymphocytes / metabolism
Mice, Inbred BALB C
Mice, Inbred DBA
Reg. No./Substance:
0/Antineoplastic Agents; 0/Antineoplastic Agents, Alkylating; 50-18-0/Cyclophosphamide

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