研究者詳細 - 瀧澤　淳

Outcomes and prognostic factors of radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) for newly diagnosed, localized extranodal NK/T-cell lymphoma, nasal type (ENKL): a cooperative study in Japan. 査読

Yamaguchi Motoko, Suzuki Ritsuro, Oguchi Masahiko, Asano Naoko, Amaki Jun, Maeda Takeshi, Kubota Nobuko, Kobayashi Yukio, Ueda Kyoko, Miyazaki Kana, Tomita Naoto, Sekiguchi Nodoka, Takizawa Jun, Saito Bungo, Murayama Tohru, Ando Toshihiko, Wada Hideho, Hyo Rie, Hasegawa Masatoshi, Katayama Naoyuki

JOURNAL OF CLINICAL ONCOLOGY 34 ( 15 ) 2016年5月

High-dose chemotherapy followed by autologous stem cell transplantation for relapsed/refractory primary mediastinal large B-cell lymphoma 査読

T. Aoki, K. Shimada, R. Suzuki, K. Izutsu, A. Tomita, Y. Maeda, J. Takizawa, K. Mitani, T. Igarashi, K. Sakai, K. Miyazaki, K. Mihara, K. Ohmachi, N. Nakamura, H. Takasaki, H. Kiyoi, S. Nakamura, T. Kinoshita, M. Ogura

BLOOD CANCER JOURNAL 5 2015年12月

Fatal tracheal aspergillosis during rituximab combined chemotherapy for diffuse large B-cell lymphoma that developed after lung transplantation 査読

K. Kawamoto, Y. Shibasaki, S. Sato, H. Nemoto, J. Takizawa, M. Narita, M. Tsuchida, H. Sone, M. Masuko

TRANSPLANT INFECTIOUS DISEASE 17 ( 6 ) 872 - 875 2015年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-BLACKWELL

Invasive tracheal aspergillosis (ITA) is an infection that is unique to patients who have undergone lung transplantation (LT). Although the activity of this disease often appears on imaging, we encountered a case of ITA that became exacerbated, despite few computed tomography (CT) findings, during rituximab combined chemotherapy for diffuse large B-cell lymphoma. ITA developed during immunosuppressive therapy after LT. Because CT findings may show false-negative results, bronchoscopy is recommended for such cases.

DOI： 10.1111/tid.12458

Possible Involvement of Lung Cells Harboring an Abnormal Karyotype in the Pathogenesis of Pulmonary Alveolar Proteinosis Associated with Myelodysplastic Syndrome.

Moriyama M, Yano T, Furukawa T, Takada T, Ushiki T, Masuko M, Takizawa J, Sone H, Tazawa R, Saijo Y, Ishii H, Nakata K

Ann Am Thorac Soc 12 ( 8 ) 1251 - 1253 2015年8月

The association of level of reduction of Wilms' tumor gene 1 mRNA transcript in bone marrow and outcome in acute myeloid leukemia patients. 査読国際誌

Shibasaki Y, Seki Y, Tanaka T, Miyakoshi S, Fuse K, Kozakai T, Kobayashi H, Ushiki T, Abe T, Yano T, Moriyama M, Kuroha T, Isahai N, Takizawa J, Narita M, Koyama S, Furukawa T, Sone H, Masuko M

Leukemia research 39 ( 6 ) 667 - 671 2015年6月

Late onset post-transfusion hepatitis E developing during chemotherapy for acute promyelocytic leukemia. 査読

Fuse K, Matsuyama Y, Moriyama M, Miyakoshi S, Shibasaki Y, Takizawa J, Furukawa T, Fuse I, Matsumura H, Uchida S, Takahashi Y, Kamimura K, Abe H, Suda T, Aoyagi Y, Sone H, Masuko M

Internal medicine (Tokyo, Japan) 54 ( 6 ) 657 - 661 2015年

Prognostic significance of pleural or pericardial effusion and the implication of optimal treatment in primary mediastinal large B-cell lymphoma: a multicenter retrospective study in Japan 査読

Tomohiro Aoki, Koji Izutsu, Ritsuro Suzuki, Chiaki Nakaseko, Hiroshi Arima, Kazuyuki Shimada, Akihiro Tomita, Makoto Sasaki, Jun Takizawa, Kinuko Mitani, Tadahiko Igarashi, Yoshinobu Maeda, Noriko Fukuhara, Fumihiro Ishida, Nozomi Niitsu, Ken Ohmachi, Hirotaka Takasaki, Naoya Nakamura, Tomohiro Kinoshita, Shigeo Nakamura, Michinori Ogura

HAEMATOLOGICA 99 ( 12 ) 1817 - 1825 2014年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：FERRATA STORTI FOUNDATION

The prognosis of patients with primary mediastinal large B-cell lymphoma has improved over recent years. However, the optimal treatment strategy including the role of radiotherapy remains unknown. We retrospectively analyzed the clinical outcomes of 345 patients with newly diagnosed primary mediastinal large B-cell lymphoma in Japan. With a median follow up of 48 months, the overall survival at four years for patients treated with R-CHOP (n=187), CHOP (n=44), DA-EPOCH-R (n=9), 2nd- or 3rd-generation regimens, and chemotherapy followed by autologous stem cell transplantation were 90%, 67%, 100%, 91% and 92%, respectively. Focusing on patients treated with R-CHOP, a higher International Prognostic Index score and the presence of pleural or pericardial effusion were identified as adverse prognostic factors for overall survival in patients treated with R-CHOP without consolidative radiotherapy (IPI: hazard ratio 4.23, 95% confidence interval 1.48-12.13, P=0.007; effusion: hazard ratio 4.93, 95% confidence interval 1.37-17.69, P=0.015). Combined with the International Prognostic Index score and the presence of pleural or pericardial effusion for the stratification of patients treated with R-CHOP without radiotherapy, patients with lower International Prognostic Index score and the absence of effusion comprised approximately one-half of these patients and could be identified as curable patients (95% overall survival at 4 years). The DA-EPOCH-R regimen might overcome the effect of these adverse prognostic factors. Our simple indicators of International Prognostic Index score and the presence of pleural or pericardial effusion could stratify patients with primary mediastinal large B-cell lymphoma and help guide selection of treatment.

DOI： 10.3324/haematol.2014.111203

Activation of the Leukemia Plasmacytoid Dendritic Cell Line PMDC05 by Toho-1, a Novel IDO Inhibitor 査読

Akie Yamahira, Miwako Narita, Minami Iwabuchi, Takayoshi Uchiyama, Shunpei Iwaya, Rie Ohiwa, Yoshinori Nishizawa, Takafumi Suzuki, Yusaku Yokoyama, Shigeo Hashimoto, Jun Takizawa, Hirohito Sone, Masuhiro Takahashi

ANTICANCER RESEARCH 34 ( 8 ) 4021 - 4028 2014年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：INT INST ANTICANCER RESEARCH

Background/Aim: Indoleamine-2,3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan metabolism and plays an immunosuppressive role. Antigen-presenting cells, when activated, increase the expression of IDO, which results in the suppression of subsequent immune reaction. A novel IDO inhibitor, Toho-1, was explored for its applicability to immunotherapy. Materials and Methods: We investigated the effects of Toho-1 on antigen presentation and antigen-specific cytotoxic T-lymphocyte-inducing ability of leukemia plasmacytoid dendritic cell line PMDC05, which was established in our laboratory. Results: While antigen presentation-associated molecules in PMDC05 cells were increased by stimulation with lipopolysaccharide and interferon-gamma, IDO mRNA and protein expression were also enhanced. Such treatment of PMDC05 cells in combination with Toho-1 enhanced the antigen-presenting and CTL-inducing ability of PMDC05 cells. Conclusion: These findings suggest the ability of Toho-1 to potentiate antigen-presenting cells and its applicability in immunotherapy of cancer.

Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways 査読

Harumi Kato, Kennosuke Karube, Kazuhito Yamamoto, Jun Takizawa, Shinobu Tsuzuki, Yasushi Yatabe, Teru Kanda, Miyuki Katayama, Yukiyasu Ozawa, Kenji Ishitsuka, Masataka Okamoto, Tomohiro Kinoshita, Koichi Ohshima, Shigeo Nakamura, Yasuo Morishima, Masao Seto

CANCER SCIENCE 105 ( 5 ) 537 - 544 2014年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly (EBV[+]DLBCL-E) is classified as a subtype of DLBCL. Until now, its molecular pathogenesis has remained unknown. To identify pathways characteristic of EBV(+)DLBCL-E, gene expression profiling of five EBV(+)DLBCL-E and seven EBV-negative DLBCL (EBV[-]DLBCL) cases was undertaken using human oligonucleotide microarray analysis. Gene set enrichment analysis and gene ontology analysis showed that gene sets of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and nuclear factor kappa B (NF-B) pathways were enriched in EBV(+)DLBCL-E cases. To confirm the results of the expression profiles, in vitro analysis was performed. Expression profiling analysis showed that high activation of the JAK-STAT and NF-B pathways was induced by EBV infection into DLBCL cell lines. Activation of the NF-B pathway was confirmed in EBV-infected cell lines using an electrophoretic mobility shift assay. Western blot analysis revealed an increased protein expression level of phosphorylated signal transducer and activator of transcription 3 (STAT3) in an EBV-infected cell line. Protein expression of phosphorylated STAT3 was frequently observed in lymphoma cells of EBV(+)DLBCL-E clinical samples using immunohistochemistry (EBV[+]DLBCL-E: 80.0% [n=20/25] versus EBV[-]DLBCL: 38.9% [n=14/36]; P=0.001). The results of the present study suggest that activation of the JAK-STAT and NF-B pathways was characteristic of EBV(+)DLBCL-E, which may reflect the nature of EBV-positive tumor cells. Targeting these pathways as therapies might improve clinical outcomes of EBV(+)DLBCL-E.

DOI： 10.1111/cas.12389

Early Diagnosis of Hepatic Intravascular Lymphoma: A Case Report and Literature Review 査読

Hiroyuki Abe, Kenya Kamimura, Maiko Mamizu, Yasuhiko Shibazaki, Takanobu Ishiguro, Shin-ichi Katada, Yu-ki Nishiyama, Yoshifumi Takahashi, Yu-ya Hatano, Ken-ichi Mizuno, Yukari Watanabe, Aiko Nagashima, Jun Takizawa, Manabu Takeuchi, Hirokazu Kawai, Minoru Nomoto, Hirohito Sone, Masatoyo Nishizawa, Yutaka Aoyagi

INTERNAL MEDICINE 53 ( 6 ) 587 - 593 2014年

記述言語：英語出版者・発行元：JAPAN SOC INTERNAL MEDICINE

Hepatic intravascular large B-cell lymphoma (IVL) is a rare disease entity that involves invasion into various organs. Due to the aggressive behavior and poor prognosis of the disease and the difficulty in making an early diagnosis, some cases are diagnosed at autopsy. Early suspicion and the use of imaging studies and liver biopsies are key for diagnosing IVL; however, no reports have described the results of imaging studies due to the limited number of cases. We herein report the results of imaging studies of hepatic IVL, including the findings PET-CT, dynamic-CT, EOB-MRI and CEUS. These results may help physicians to make an early diagnosis and improve the prognosis.

DOI： 10.2169/internalmedicine.53.1812

Manifestations of Fulminant CD8 T-cell Post-transplant Lymphoproliferative Disorder Following the Administration of Rituximab for Lymphadenopathy with a High Level of Epstein-Barr Virus (EBV) Replication after Allogeneic Hematopoietic Stem Cell Transplantation 査読

Tomoyuki Tanaka, Jun Takizawa, Shukuko Miyakoshi, Takashi Kozakai, Kyoko Fuse, Yasuhiko Shibasaki, Masato Moriyama, Koichi Ohshima, Ken Toba, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

INTERNAL MEDICINE 53 ( 18 ) 2115 - 2119 2014年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN SOC INTERNAL MEDICINE

We herein report the case of a 22-year-old woman with severe aplastic anemia who underwent allogeneic hematopoietic stem cell transplantation (HSCT). After HSCT, the Epstein-Barr virus (EBV)-DNA load in the peripheral blood gradually increased, and the patient presented with a fever and lymphadenopathy on day 56 post-HSCT. Although we administered rituximab, her clinical condition worsened. After rituximab treatment, CD8 T-cells emerged and became dominant in the peripheral blood, some of which were positive on an EBV-specific tetramer analysis. However, an open biopsy of the lymphadenopathy lesions revealed the CD8 T-cells to be infected with EBV, exhibiting proliferation with oligoclonality. The patient ultimately died of multiple organ failure on day 99 post-HSCT.

DOI： 10.2169/internalmedicine.53.2384

Successful treatment of severe newly diagnosed immune thrombocytopenia involving an alveolar hemorrhage with combination therapy consisting of romiplostim, rituximab and vincristine. 査読

Okazuka K, Masuko M, Matsuo Y, Miyakoshi S, Tanaka T, Kozakai T, Kobayashi H, Fuse K, Shibasaki Y, Moriyama M, Takizawa J, Fuse I, Toba K, Furukawa T

Intern Med 52 ( 11 ) 1239 - 1242 2013年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：The Japanese Society of Internal Medicine

A 51-year-old man was admitted due to a severe bleeding tendency. After he was diagnosed with immune thrombocytopenia (ITP), several therapies, including steroids, steroid pulse, vincristine and rituximab, were administered; however, the patient's bleeding symptoms were not sufficiently controllable with these treatments. Subsequently, a diffuse alveolar hemorrhage was observed. Treatment with a thrombopoietin receptor agonist, romiplostim, was initiated to prevent lethal hemorrhaging, although the efficacy of thrombopoietic receptor agonists in such emergency situations has not been elucidated. The initiation of romiplostim achieved prompt remission in platelets. This case suggests that combination therapy with romiplostim, rituximab and vincristine is effective in cases of newly diagnosed severe therapy-resistant ITP.<br>

DOI： 10.2169/internalmedicine.52.0080

CiNii Article

その他リンク： http://search.jamas.or.jp/link/ui/2014315593

MYC rearrangements are useful for predicting outcomes following rituximab and chemotherapy: Multicenter analysis of Japanese patients with diffuse large B-cell lymphoma 査読

Minoru Kojima, Hidekazu Nishikii, Jun Takizawa, Sadao Aoki, Masayuki Noguchi, Shigeru Chiba, Kiyoshi Ando, Naoya Nakamura

Leukemia and Lymphoma 54 ( 10 ) 2149 - 2154 2013年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and it has several morphologic and clinicopathologic variants. The prognosis of DLBCL can vary according to specific genetic and immunophenotypic abnormalities. The aim of this study was to investigate the prognostic impact of previously identified prognostic factors, such as activated B cell-like immunophenotype, CD5, BCL2 and MYC rearrangement (MYC-R), in patients treated with rituximab. We retrospectively analyzed the prognosis of 100 patients with DLBCL (median age, 66.5 years) treated with rituximab-containing chemotherapy. The 3-year overall survival (OS) and progression-free survival (PFS) were 66% and 62%. Outcomes were significantly worse in patients with MYC-R in 3-year OS (50% vs. 67.8%, p = 0.043) and PFS (30% vs. 57.8%, p = 0.003), and multivariate analysis showed that this finding was independent of the International Prognostic Index (IPI). Immunostaining by Muris algorithm had the highest predictive power among the three algorithms. However, other previously reported prognostic factors, such as BCL2 and CD5, were not good predictors of outcomes in these patients. In conclusion, our data suggest that fluorescence in situ hybridization (FISH) analysis for MYC-R can predict outcomes in response to rituximab-containing chemotherapy in Japanese patients with DLBCL. © 2013 Informa UK, Ltd.

DOI： 10.3109/10428194.2013.771398

Scopus

Epstein-Barr virus-associated primary central nervous system cytotoxic T-cell lymphoma. 査読国際誌

Ogura R, Aoki H, Natsumeda M, Shimizu H, Kobayashi T, Saito T, Takizawa J, Okamoto K, Hasegawa G, Umezu H, Ohshima K, Takahashi H, Fujii Y, Kakita A

Neuropathology : official journal of the Japanese Society of Neuropathology 33 ( 4 ) 436 - 441 2013年8月

Pretreatment EBV-DNA Copy Number Is Predictive of Response and Toxicities to SMILE Chemotherapy for Extranodal NK/T-cell Lymphoma, Nasal Type 査読

Yoshinori Ito, Hiroshi Kimura, Yoshinobu Maeda, Chizuko Hashimoto, Fumihiro Ishida, Koji Izutsu, Noriyasu Fukushima, Yasushi Isobe, Jun Takizawa, Yuichi Hasegawa, Hajime Kobayashi, Seiichi Okamura, Hikaru Kobayashi, Motoko Yamaguchi, Junji Suzumiya, Rie Hyo, Shigeo Nakamura, Keisei Kawa, Kazuo Oshimi, Ritsuro Suzuki

CLINICAL CANCER RESEARCH 18 ( 15 ) 4183 - 4190 2012年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC CANCER RESEARCH

Purpose: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is an Epstein-Barr virus (EBV)-associated lymphoma for which a new chemotherapeutic regimen called SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) recently showed promising results.
Experimental Design: The amount of EBV-DNA was prospectively measured in whole-blood and plasma samples by real-time quantitative PCR from 26 patients registered in the SMILE phase II study.
Results: Before treatment, the EBV-DNA was detected in 22 samples of whole blood with a median number of 3,691 copies/mL (range: 0-1.14 x 10(7)), but 15 samples of plasma with a median of 867 copies/mL (range: 0-1.27 x 10(7)). Results of these 2 measurements of EBV-DNA well correlated (R-2 = 0.994, P < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 10(5) copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P = 0.007) and in patients with less than 10(4) copies/mL of EBV-DNA in plasma (95% vs. 29%, P = 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 10(5) copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P = 0.007) than that of others and in patients with 10(4) copies/mL or more in plasma (86% vs. 26%, P = 0.002).
Conclusions: These findings suggest that whole blood is more sensitive for clinical use than plasma. The EBV-DNA amount in whole blood was useful for predicting tumor response, toxicity, and prognosis after SMILE chemotherapy for ENKL. Clin Cancer Res; 18(15); 4183-90. (C)2012 AACR.

DOI： 10.1158/1078-0432.CCR-12-1064

IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG-type autoantibody production in autoimmune pulmonary alveolar proteinosis 査読

Takahito Nei, Shinya Urano, Natsuki Motoi, Jun Takizawa, Chinatsu Kaneko, Hiroko Kanazawa, Ryushi Tazawa, Kazuhide Nakagaki, Kiyoko S. Akagawa, Keiichi Akasaka, Toshio Ichiwata, Arata Azuma, Koh Nakata

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 302 ( 9 ) L959 - L964 2012年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER PHYSIOLOGICAL SOC

Nei T, Urano S, Motoi N, Takizawa J, Kaneko C, Kanazawa H, Tazawa R, Nakagaki K, Akagawa KS, Akasaka K, Ichiwata T, Azuma A, Nakata K. IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG-type autoantibody production in autoimmune pulmonary alveolar proteinosis. Am J Physiol Lung Cell Mol Physiol 302: L959-L964, 2012. First published February 24, 2012; doi: 10.1152/ajplung.00378.2011.-The granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody (GMAb) is the causative agent underlying autoimmune pulmonary alveolar proteinosis (aPAP). It consists primarily of the IgG isotype. At present, information on other isotypes of the autoantibody is limited. We detected serum the IgM isotype of GMAb (IgM-GMAb) in more than 80% of patients with aPAP and 22% of healthy subjects, suggesting that a continuous antigen pressure may be present in most patients. Levels of the IgM isotype were weakly correlated with IgG-GMAb levels but not IgA-GMAb, suggesting that its production may be associated with that of IgG-GMAb. The mean binding avidity to GM-CSF of the IgM isotype was 100-fold lower than the IgG-GMAb isotype, whereas the IC50 value for neutralizing capacity was 20,000-fold higher than that of IgG-GMAb, indicating that IgM-GMAb is only a very weak neutralizer of GM-CSF. In bronchoalveolar lavage fluid from nine patients, IgG-GMAb was consistently detected, but IgM-GMAb was under the detection limit in most patients, confirming that IgM-GMAb is functionally a bystander in the pathogenesis of aPAP. It rather may be involved in the mechanism for development of IgG-GMAb in vivo.

DOI： 10.1152/ajplung.00378.2011

Does more intensive therapy have effects on mantle cell lymphoma? A clinical experience from the Lymphoma Treatment Study Group in Japan 査読

Katsuhiro Miura, Hirotaka Takasaki, Hideki Tsujimura, Masatoshi Kanno, Yoshinobu Maeda, Naoto Tomita, Kazue Takai, Yasufumi Masaki, Jun Takizawa, Hiraku Mori, Yasushi Terasaki, Takashi Yoshida, Jin Takeuchi, Shigeki Motomura

INTERNATIONAL JOURNAL OF HEMATOLOGY 93 ( 5 ) 684 - 686 2011年5月

Multifocal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: a case report 査読

Tokuhide Oyama, Jun Takizawa, Naoya Nakamura, Sadao Aoki, Yoshifusa Aizawa, Haruki Abe

JAPANESE JOURNAL OF OPHTHALMOLOGY 55 ( 3 ) 304 - 306 2011年5月

Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis 査読

Daisuke Ennishi, Yoshinobu Maeda, Nozomi Niitsu, Minoru Kojima, Koji Izutsu, Jun Takizawa, Shigeru Kusumoto, Masataka Okamoto, Masahiro Yokoyama, Yasushi Takamatsu, Kazutaka Sunami, Akira Miyata, Kayoko Murayama, Akira Sakai, Morio Matsumoto, Katsuji Shinagawa, Akinobu Takaki, Keitaro Matsuo, Tomohiro Kinoshita, Mitsune Tanimoto

BLOOD 116 ( 24 ) 5119 - 5125 2010年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC HEMATOLOGY

The influence of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma in the rituximab era is unclear. Thus, we analyzed 553 patients, 131 of whom were HCV-positive and 422 of whom were HCV-negative, with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-like chemotherapy. Survival outcomes and hepatic toxicity were compared according to HCV infection. The median follow-up was 31 and 32 months for patients who were HCV-positive and HCV-negative, respectively. HCV infection was not a significant risk factor for prognosis (3-year progression-free survival, 69% vs 77%, P = .22; overall survival, 75% vs 84%, P = .07). Of 131 patients who were HCV-positive, 36 (27%) had severe hepatic toxicity (grade 3-4), compared with 13 of 422 (3%) patients who were HCV-negative. Multivariate analysis revealed that HCV infection was a significant risk factor for severe hepatic toxicity (hazard ratio: 14.72; 95% confidence interval, 6.37-34.03; P < .001). An exploratory analysis revealed that pretreatment transaminase was predictive of severe hepatic toxicity. HCV-RNA levels significantly increased during immunochemotherapy (P = .006). These results suggest that careful monitoring of hepatic function and viral load is indicated during immunochemotherapy for HCV-positive patients. (Blood. 2010;116(24):5119-5125)

DOI： 10.1182/blood-2010-06-289231