研究者詳細 - 遠西　大輔

論文 - 遠西　大輔

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Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy. 国際誌

D Ennishi, H Asai, Y Maeda, K Shinagawa, K Ikeda, M Yokoyama, Y Terui, K Takeuchi, T Yoshino, K Matsuo, K Hatake, M Tanimoto

Annals of oncology : official journal of the European Society for Medical Oncology 21 ( 6 ) 1217 - 1221 2010年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: A recent laboratory study indicated that statins impaired the antitumor effects of rituximab by inducing conformational changes in CD20. Although these findings raised significant concerns about statin use during rituximab treatment, their clinical significance is unclear. PATIENTS AND METHODS: We conducted a retrospective study investigating the effects of statins on the prognosis of diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Newly diagnosed DLBCL patients were analyzed (n = 256), including 35 patients taking statins. RESULTS: The 3-year progression-free survival rates were 84% and 73% (P = 0.38), while the overall survival rates were 89% and 78% (P = 0.28) for those patients treated with and without statins, respectively. After adjusting for the International Prognostic Index and serum cholesterol level, statin use was not associated with prognosis. CONCLUSIONS: These results indicate that statins do not influence the clinical prognosis of DLBCL treated with RCHOP. Further studies with larger numbers of patients are warranted to confirm the prognostic significance of statins for patients with DLBCL receiving rituximab-containing chemotherapy.

DOI： 10.1093/annonc/mdp490

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Incidental detection of acute lymphoblastic leukemia on [18F]fluorodeoxyglucose positron emission tomography. 国際誌

Daisuke Ennishi, Yoshinobu Maeda, Masami Niiya, Katsuji Shinagawa, Mitsune Tanimoto

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27 ( 36 ) e269-70 2009年12月

An imaging-based rapid evaluation method for complement-dependent cytotoxicity discriminated clinical response to rituximab-containing chemotherapy. 国際誌

Yuji Mishima, Natsuhiko Sugimura, Yuko Matsumoto-Mishima, Yasuhito Terui, Kengo Takeuchi, Suzuka Asai, Daisuke Ennishi, Hiroaki Asai, Masahiro Yokoyama, Kiyotsugu Kojima, Kiyohiko Hatake

Clinical cancer research : an official journal of the American Association for Cancer Research 15 ( 10 ) 3624 - 32 2009年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Rituximab has greatly improved the efficacy of chemotherapy regimens for CD20-positive non-Hodgkin's lymphoma. However, although several mechanisms of action of rituximab have been identified, the exact therapeutic functions of these mechanisms remains to be clarified. In addition, there is no established prognostic marker to predict an individual response. This study verified the validity of ex vivo complement-dependent cytotoxicity (CDC) susceptibility as a predictor of pathologic tumor regression in patients undergoing rituximab-containing chemotherapy and examined whether CDC contributes to the mechanism of action of rituximab. EXPERIMENTAL DESIGN: A rapid assay system was established to evaluate the tumoricidal activity of rituximab using a living cell-imaging technique. We analyzed lymph node biopsies obtained from 234 patients with suspected lymphomas and estimated the association between CDC susceptibility and the response to rituximab-containing chemotherapy in diffuse large B-cell lymphoma and follicular lymphoma. RESULTS: This study revealed that CDC susceptibility of lymphoma cells freshly obtained from patients was strongly associated with response to rituximab-containing chemotherapy in both diffuse large B-cell lymphoma and follicular lymphoma. This correlation was not apparent in cases that received chemotherapy without rituximab. CONCLUSIONS: The system that we have established allows a successful assessment of rituximab-induced CDC and can distinguish cases refractory to rituximab-containing chemotherapy. The association between CDC susceptibility and therapy response suggests that CDC is pivotal in the ability of chemotherapy including rituximab to induce remission.

DOI： 10.1158/1078-0432.CCR-08-1536

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Soluble interleukin-2 receptor retains prognostic value in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP (RCHOP) therapy. 国際誌

D Ennishi, M Yokoyama, Y Terui, H Asai, S Sakajiri, Y Mishima, S Takahashi, H Komatsu, K Ikeda, K Takeuchi, M Tanimoto, K Hatake

Annals of oncology : official journal of the European Society for Medical Oncology 20 ( 3 ) 526 - 33 2009年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Soluble interleukin-2 receptor (SIL-2R) is known to be a prognostic parameter in patients with diffuse large B-cell lymphoma (DLBCL) receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy. However, its prognostic value has not been well known since the introduction of rituximab. PATIENTS AND METHODS: We retrospectively evaluated the prognostic impact of SIL-2R in 228 DLBCL patients, comparing 141 rituximab-combined CHOP (RCHOP)-treated patients with 87 CHOP-treated patients as a historical control. RESULTS: Patients with high serum SIL-2R showed significantly poorer event-free survival (EFS) and overall survival (OS) than patients with low SIL-2R in both the RCHOP group (2-year EFS, 66% versus 92%, P<0.001; OS, 82% versus 95%, P=0.005) and the CHOP group (2-year EFS, 40% versus 82%; OS, 61% versus 90%, both P<0.001). Multivariate analysis including the five parameters of International Prognostic Index (IPI) and two-categorized IPI revealed that SIL-2R was an independent prognostic factor for EFS and OS in the RCHOP group as well as in the CHOP group. CONCLUSIONS: Our results demonstrate that SIL-2R retains its prognostic value in the rituximab era. The prognostic value of SIL-2R in DLBCL patients receiving rituximab-combined chemotherapy should be reassessed on a larger scale and by long-term follow-up.

DOI： 10.1093/annonc/mdn677

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CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy. 国際誌

D Ennishi, K Takeuchi, M Yokoyama, H Asai, Y Mishima, Y Terui, S Takahashi, H Komatsu, K Ikeda, M Yamaguchi, R Suzuki, M Tanimoto, K Hatake

Annals of oncology : official journal of the European Society for Medical Oncology 19 ( 11 ) 1921 - 6 2008年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Several biomarkers indicating poor prognosis have been reassessed in patients receiving rituximab combination chemotherapy for diffuse large B-cell lymphoma (DLBCL). However, few studies have investigated outcome in relation to a combination of these biomarkers. In addition, no large-scale studies have reassessed the outcome of patients with CD5-positive DLBCL treated with rituximab. PATIENTS AND METHODS: We conducted a retrospective study and investigated the predictive value of three biomarkers -- BCL2, germinal center (GC) phenotype and CD5 -- in 121 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone. RESULTS: CD5-positive patients showed significantly poorer event-free survival (EFS) and overall survival (OS) than CD5-negative patients (2-year EFS, 18% versus 73%, P < 0.001; 2-year OS, 45% versus 91%, P = 0.001). However, no significant difference in outcome according to BCL2 or GC phenotype was observed. Multivariate analysis revealed that CD5 expression was a significant prognostic factor for EFS [hazard ratio 14.2, 95% confidence interval (CI) 4.7-43.2] and OS (hazard ratio 20.3, 95% CI 3.6-114.4). CONCLUSIONS: CD5 expression was the only significant prognostic factor among the biomarkers examined in this study. Further studies with larger numbers are warranted to confirm the prognostic significance of CD5 expression for patients with DLBCL receiving rituximab-containing chemotherapy.

DOI： 10.1093/annonc/mdn392

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Does rituximab really induce hepatitis C virus reactivation? 国際誌

Daisuke Ennishi, Masahiro Yokoyama, Yasuhito Terui, Kengo Takeuchi, Kazuma Ikeda, Mitsune Tanimoto, Kiyohiko Hatake

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 26 ( 28 ) 4695 - 6 2008年10月

Increased incidence of interstitial pneumonia by CHOP combined with rituximab.

Daisuke Ennishi, Yasuhito Terui, Masahiro Yokoyama, Yuko Mishima, Shunji Takahashi, Kengo Takeuchi, Kazuma Ikeda, Mitsune Tanimoto, Kiyohiko Hatake

International journal of hematology 87 ( 4 ) 393 - 397 2008年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Several authors have reported interstitial pneumonia (IP) during rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy, while others have encountered Pneumocystis jirovecii pneumonia during rituximab-combined bi-weekly CHOP. Herein, we report that 13 of 90 (14%) patients developed IP during R-CHOP therapy, compared with none of 105 patients treated with CHOP alone as a historical control. There were no differences in baseline data between patients undergoing the two therapies. Among R-CHOP-treated patients, serum beta-D-glucan was increased in 8 of 12 (75%) IP patients compared with none of 30 non-IP patients examined. In five IP patients who underwent sputum evaluation, two were positive for P. jirovecii by the polymerase chain reaction and another two were positive for Candida albicans. No other organisms were detected as causative pathogens. Treatment with steroids, sulfamethoxazole-trimethoprim (ST), and antifungals was effective. Our results suggest that R-CHOP raises the incidence of IP, possibly through increasing the susceptibility to P. jirovecii and fungal infection. The need for prophylactic antifungals and ST during R-CHOP should be evaluated by randomized controlled trials.

DOI： 10.1007/s12185-008-0066-7

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Monitoring serum hepatitis C virus (HCV) RNA in patients with HCV-infected CD20-positive B-cell lymphoma undergoing rituximab combination chemotherapy. 国際誌

Daisuke Ennishi, Yasuhito Terui, Masahiro Yokoyama, Yuko Mishima, Shunji Takahashi, Kengo Takeuchi, Hiroaki Okamoto, Mitsune Tanimoto, Kiyohiko Hatake

American journal of hematology 83 ( 1 ) 59 - 62 2008年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Several studies have shown that the frequency of hepatitis C virus (HCV) infection is high in patients with B-cell non-Hodgkin's lymphoma (NHL). In these studies, liver dysfunction during chemotherapy has been demonstrated, but changes in HCV ribonucleic acid (RNA) levels during chemotherapy have not been well documented. In this study, we monitored serum HCV RNA levels and liver function in five HCV-infected patients with B-cell NHL undergoing treatment with rituximab-combination chemotherapy. Increased HCV RNA levels during or after the chemotherapy were observed in all five patients, and a significant increase in transaminases was seen in one case. In this case, serum HCV RNA level dramatically decreased at the time of the increase of transaminases, and this suggested that the cause of liver damage was an immune reaction against hepatocytes with HCV and not any anticancer drug induced liver toxicity. Monitoring of serum HCV RNA levels and transaminases may be helpful to understand the cause of liver dysfunction in patients receiving chemotherapy. However, increases of HCV viral load were not associated with the occurrence of liver dysfunction in this study. Further studies will be necessary to investigate more fully the relationship between changes in HCV viral load and liver function during chemotherapy for HCV-infected patients.

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Rituximab plus CHOP as an initial chemotherapy for patients with disseminated MALT lymphoma. 国際誌

Daisuke Ennishi, Masahiro Yokoyama, Yuko Mishima, Chie Watanabe, Yasuhito Terui, Shunji Takahashi, Kengo Takeuchi, Kazuma Ikeda, Mitsune Tanimoto, Kiyohiko Hatake

Leukemia & lymphoma 48 ( 11 ) 2241 - 3 2007年11月

A case of acute promyelocytic leukemia during gefitinib treatment.

Daisuke Ennishi, Nobuo Sezaki, Tadasi Senoo, Yasuhito Terui, Kiyohiko Hatake, Norihiko Hino

International journal of hematology 84 ( 3 ) 284 - 5 2006年10月

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