研究者詳細 - 瀧澤　淳

論文 - 瀧澤　淳

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Safety and efficacy of acalabrutinib and obinutuzumab in treatment-naive chronic lymphocytic leukemia: a Japanese phase 1 study. 国際誌

Jun Takizawa, Takanori Teshima, Daisuke Ennishi, Satoshi Ichikawa, Ritsuro Suzuki, Akira Kojima, Yusuke Takahashi, Nobuya Hayashi, Hisashi Kawasumi, Kosho Murayama, Patricia Cheung, Toshio Kawata, Koji Izutsu

Leukemia & lymphoma 65 ( 11 ) 1586 - 1594 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

This report focuses on part 3 of a multicenter, open-label, phase 1 study (NCT03198650) assessing the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of acalabrutinib plus obinutuzumab in Japanese patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL). Ten patients were included; median age was 68 years. With a median treatment duration of 27.2 months, treatment-emergent adverse events (AEs) occurred in all patients (grade ≥3, 70%), and the most common AEs were anemia and headache (40% each). One patient had a grade 4 AE of neutropenia (the only dose-limiting toxicity). PK results suggested no marked effects of concomitant obinutuzumab treatment on the exposure of acalabrutinib. PD assessment indicated that combination therapy provided >98% Bruton tyrosine kinase (BTK) occupancy. Overall response rate (ORR) was 100% with median duration of response (DoR) and median progression-free survival (PFS) not reached. Treatment with acalabrutinib plus obinutuzumab was generally safe and efficacious in adult Japanese patients with TN CLL.

DOI： 10.1080/10428194.2024.2370436

Alemtuzumab monotherapy for T-cell prolymphocytic leukemia: an observational study in Japan.

Motoko Yamaguchi, Noriko Fukuhara, Jun Takizawa, Kenji Ishitsuka, Akihiko Yokohama, Kana Miyazaki, Yuma Nato, Satoshi Ichikawa, Masaki Mitobe, Kodai Shima, Yuri Miyazawa, Koji Izutsu, Ritsuro Suzuki, Hirokazu Nagai, Naoya Nakamura

Journal of clinical and experimental hematopathology : JCEH 2024年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Alemtuzumab is recommended as first-line and second-line therapies for T-cell prolymphocytic leukemia (T-PLL). This study retrospectively evaluated the efficacy and safety of alemtuzumab in nine Japanese patients with T-PLL at five participating institutions who were treated between January 2015 and August 2023. The median age at first administration of alemtuzumab was 72 years (range, 39 to 78). Two patients were treatment naïve, and seven had been treated with a median of one (range, 1 to 3) prior systemic therapy. Six patients were refractory to their most recent therapy. Three patients completed 12 weeks of treatment. The overall response rate and the complete response (CR) rate were 78% and 11%, respectively. Among the six patients who achieved a partial response, two achieved clinical CR but did not undergo bone marrow examination. One patient also achieved clinical CR but did not undergo CT or bone marrow examination for response evaluation. The median progression-free survival time was 8.1 months (95% confidence interval, 0.9 to 18.6). Three patients received readministration of alemtuzumab monotherapy after disease progression. There were no treatment-related deaths. The grade 3 or 4 nonhematologic adverse events included infusion reaction (grade 3, n = 2), cytomegalovirus reactivation (grade 3, n = 2), and pulmonary edema (grade 3, n = 1). One patient experienced Epstein‒Barr virus-positive diffuse large B-cell lymphoma 15 months after the last dose of alemtuzumab. These results confirm that the efficacy and safety of alemtuzumab monotherapy in Japanese patients are comparable to those previously reported.

DOI： 10.3960/jslrt.24028

Autologous HSCT with novel agent-based induction and consolidation followed by lenalidomide maintenance for untreated multiple myeloma. 国際誌

Yasuo Mori, Jun Takizawa, Yuna Katsuoka, Naoki Takezako, Koji Nagafuji, Hiroshi Handa, Junya Kuroda, Kazutaka Sunami, Tomohiko Kamimura, Ryosuke Ogawa, Yoshikane Kikushige, Mine Harada, Koichi Akashi, Toshihiro Miyamoto

Cancer science 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Triplet regimen comprising proteasome inhibitors, immunomodulatory drugs, and dexamethasone (DEX) is a recommended induction/consolidation therapy for multiple myeloma (MM) patients eligible for transplant. In this Japanese phase II study conducted from 2017 to 2019, newly diagnosed MM patients aged 20-65 received four induction cycles with bortezomib (Bor), lenalidomide (Len), and DEX (VRD), followed by Bor and high-dose melphalan with autologous stem cell rescue. Subsequently, they underwent four consolidation cycles with carfilzomib, Len, and DEX (KRD), followed by Len maintenance until disease progression. A total of 141 patients were analyzed. In an intent-to-treat population, the complete or better response post induction was 19.9%, rising to 39.7%, 58.9%, and 62.4% after transplant, consolidation, and 1-year maintenance, respectively. With a median follow-up of 38 months, the 3-year progression-free survival (PFS) rate was 83.5% and the 3-year overall survival rate was 92.5%. Severe adverse events (≥grade 3) occurred in ~30% of patients; however, there was no treatment-related mortality. These findings clearly showed the tolerability and effectiveness of this protocol. Nevertheless, patients with high-risk cytogenetics showed a trend toward lower 3-year PFS than those without (77.8% vs. 89.4%, p = 0.051), and ultra-high-risk cytogenetics (≥2 high-risk cytogenetics) had an even worse prognosis, with 61.2% 3-year PFS. To overcome this situation, a more potent treatment strategy incorporating novel agents such as the CD38-antibody should be assessed in future studies.

DOI： 10.1111/cas.16158

Characteristics of chronic lymphocytic leukemia in Japan: Comprehensive analysis of the CLLRSG-01 study

Jun Takizawa, Ritsuro Suzuki, Koji Izutsu, Toru Kiguchi, Hideki Asaoku, Yoshio Saburi, Taro Masunari, Atae Utsunomiya, Kengo Takeuchi, Naoya Nakamura, Koichi Ohshima, Michaela Gruber, Ulrich Jäger, Sadao Aoki, Junji Suzumiya

International Journal of Hematology 119 ( 6 ) 686 - 696 2024年3月

Clinicopathological comparison between PTCL-TBX21 and PTCL-GATA3 in Japanese patients. 国際誌

Yasumasa Shimasaki, Hiroaki Miyoshi, Keisuke Kawamoto, Noriaki Yoshida, Tatsuzo Mishina, Kazutaka Nakashima, Teppei Imamoto, Takeshi Sugio, Eriko Yanagida, Takeharu Kato, Kyohei Yamada, Mai Takeuchi, Takaharu Suzuki, Mayuko Moritsubo, Takuya Furuta, Yoshitaka Imaizumi, Jun Takizawa, Koji Kato, Junji Suzumiya, Ritsuro Suzuki, Koichi Ohshima

Cancer medicine 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a heterogeneous disease that can be classified into the PTCL-TBX21 and PTCL-GATA3 subtypes. METHODS: In this study, we compared the clinicopathological features of PTCL-NOS in a Japanese cohort, classified using an IHC algorithm. RESULTS: One hundred patients with PTCL-NOS were categorized as having PTCL-TBX21 (n = 55), PTCL-GATA3 (n = 24), or PTCL-unclassified (n = 21). When comparing PTCL-TBX21 and PTCL-GATA3, PTCL-TBX21 showed significantly lower CD4 positivity (p = 0.047), lower counts of high endothelial venules (p = 0.032), and a tendency for a better response to initial treatment (p = 0.088). Gene expression analysis using the nCounter system showed higher expression of tumor immunity-related genes, such as PD-L1, LAG3, and IDO1, in PTCL-TBX21 than in PTCL-GATA3. PTCL-GATA3 had significantly worse overall survival (OS) than those with PTCL-TBX21 (p = 0.047), although a similar tendency was observed for progression-free survival (PFS) (p = 0.064). PTCL-GATA3 was a prognostic factor for OS in univariate analysis (HR 2.02; 95% CI, 1.09-3.77; p = 0.027), although multivariate analysis did not show significance (HR 2.07; 95% CI, 0.93-4.61; p = 0.074). In the PFS analysis, PTCL-GATA3 was an independent prognostic factor by univariate analysis (HR 1.96; 95% CI, 1.08-3.56; p = 0.027) and multivariate analysis (HR 2.34; 95% CI, 1.07-5.11; p = 0.032). CONCLUSION: The classification of PTCL-NOS into PTCL-TBX21 and PTCL-GATA3 is useful for predicting the prognosis of Japanese patients and stratifying the administration of tumor immune checkpoint inhibitors in clinical practice.

DOI： 10.1002/cam4.6793

YAP1/TAZ activity maintains vascular integrity and organismal survival. 国際誌

Shun Uemura, Masayuki Yamashita, Kazumasa Aoyama, Takako Yokomizo-Nakano, Motohiko Oshima, Miki Nishio, Masayoshi Masuko, Jun Takizawa, Hirohito Sone, Yasuhiro Yamada, Akira Suzuki, Atsushi Iwama

Biochemical and biophysical research communications 619 117 - 123 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Radiation therapy is one of the major treatment modalities for patients with cancers. However, ionizing radiation (IR) damages not only cancer cells but also the surrounding vascular endothelial cells (ECs). Hippo pathway effector genes Yap1 and Taz are the two transcriptional coactivators that have crucial roles in tissue homeostasis and vascular integrity in various organs. However, their function in adult ECs at the steady state and after IR is poorly understood. Here, we report sex- and context-dependent roles of endothelial YAP1/TAZ in maintaining vascular integrity and organismal survival. EC-specific Yap1/Taz deletion compromised systemic vascular integrity, resulting in lethal circulation failure preferentially in male mice. Furthermore, EC-specific Yap1/Taz deletion induced acute lethality upon sublethal IR that was closely associated with exacerbated systemic vascular dysfunction and circulation failure. Consistent with these findings, RNA-seq analysis revealed downregulation of tight junction genes in Yap1/Taz-deleted ECs. Collectively, our findings highlight the importance of endothelial YAP1/TAZ for maintaining adult vascular function, which may provide clinical implications for preventing organ injury after radiation therapy.

DOI： 10.1016/j.bbrc.2022.06.050

Long-term outcomes and central nervous system relapse in extranodal natural killer/T-cell lymphoma. 国際誌

Kana Miyazaki, Ritsuro Suzuki, Masahiko Oguchi, Senzo Taguchi, Jun Amaki, Takeshi Maeda, Nobuko Kubota, Dai Maruyama, Yasuhito Terui, Nodoka Sekiguchi, Jun Takizawa, Hiroyuki Tsukamoto, Tohru Murayama, Toshihiko Ando, Hiroshi Matsuoka, Masatoshi Hasegawa, Hideho Wada, Rika Sakai, Yoshihiro Kameoka, Norifumi Tsukamoto, Ilseung Choi, Yasufumi Masaki, Kazuyuki Shimada, Noriko Fukuhara, Takahiko Utsumi, Nobuhiko Uoshima, Yoshitoyo Kagami, Naoko Asano, Yasuo Ejima, Naoyuki Katayama, Motoko Yamaguchi

Hematological oncology 40 ( 4 ) 667 - 677 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL.

DOI： 10.1002/hon.2977

A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B‐cell lymphoma 査読国際誌

Yasuhito Terui, Shinya Rai, Koji Izutsu, Motoko Yamaguchi, Jun Takizawa, Junya Kuroda, Takayuki Ishikawa, Koji Kato, Youko Suehiro, Noriko Fukuhara, Ken Ohmine, Hideki Goto, Kazuhito Yamamoto, Nobuhiro Kanemura, Yasunori Ueda, Kenichi Ishizawa, Kyoya Kumagai, Atsuko Kawasaki, Tomohisa Saito, Misato Hashizume, Hirohiko Shibayama

Cancer Science 112 ( 7 ) 2845 - 2854 2021年7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

Polatuzumab vedotin (pola) is a CD79b-targeted antibody-drug conjugate delivering a potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open-label, single-arm study of pola 1.8 mg/kg, bendamustine 90 mg/m2 , rituximab 375 mg/m2 (pola + BR) Q3W for up to six cycles in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who received ≥1 prior line of therapy and were ineligible for autologous stem cell transplantation (ASCT) or experienced treatment failure with prior ASCT. Primary endpoint was complete response rate (CRR) at the end of the treatment (EOT) by positron emission tomography-computed tomography (PET-CT) using modified Lugano Response Criteria. Secondary endpoints included efficacy, safety, and pharmacokinetics. Thirty-five patients (median age 71 [range 46-86] years) were enrolled. Twenty-three (66%) patients had refractory disease, and 23 (66%) had ≥2 prior lines of therapy. At a median follow-up of 5.4 (0.7-11.9) months, patients received a median of five treatment cycles. CRR was 34.3% (95% confidence interval [CI] 19.1-52.2) at EOT. Overall response rate was 42.9% at EOT, and median progression-free survival was 5.2 months (95% CI 3.6-not evaluable). Median overall survival was not reached. No fatal adverse events (AEs) were observed. Grade 3-4 AEs were mainly hematological: anemia (37%), neutropenia (31%), white blood cell count decreased (23%), thrombocytopenia/platelet count decreased/neutrophil count decreased (20% each), and febrile neutropenia (11%). Grade 1-2 peripheral neuropathy (PN; sensory and/or motor) was reported in 14% of patients; there were no ≥grade 3 PN events. This study (JapicCTI-184048) demonstrated the efficacy and safety of pola + BR in Japanese patients with R/R DLBCL who were ineligible for ASCT.

DOI： 10.1111/cas.14937

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14937

A phase II Japanese trial of fludarabine, cyclophosphamide and rituximab for previously untreated chronic lymphocytic leukemia 査読

Koji Izutsu, Tomohiro Kinoshita, Jun Takizawa, Suguru Fukuhara, Go Yamamoto, Yasuo Ohashi, Junji Suzumiya, Kensei Tobinai

Japanese Journal of Clinical Oncology 51 ( 3 ) 408 - 415 2021年3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：Oxford University Press (OUP)

<title>Abstract</title>
<sec>
<title>Objective</title>
Fludarabine, cyclophosphamide and rituximab (FCR) is the standard regimen for fit patients with untreated CD20-positive chronic lymphocytic leukemia (CLL). However, this combination is unavailable in Japan because rituximab is not approved for CLL. We investigated the efficacy and safety of FCR in this single-arm, multicenter study designed as a bridging study to the CLL8 study by the German CLL Study Group.

</sec>
<sec>
<title>Methods</title>
The study enrolled previously untreated patients with CLL of Binet stage B or C with active disease. Patients with a Cumulative Illness Rating Scale score of ≤6 and creatinine clearance of ≥70 ml/min were eligible. Patients received 6 cycles of FCR every 28 days and were followed for up to 1 year.

</sec>
<sec>
<title>Results</title>
Seven patients were enrolled. The best overall response rate according to the 1996 NCI-WG Guidelines, the primary endpoint of the study, was 71.4% (95% confidence interval, 29.0–96.3%), with one patient achieving complete response. No deaths or progression occurred during follow-up. The main adverse event was hematotoxicity. CD4-positive T-cell count decreased in all patients; most patients showed no reduction in serum immunoglobulin G.

</sec>
<sec>
<title>Conclusion</title>
Although the number of patients was limited, FCR appears to be effective with manageable toxicity for treatment-naïve fit Japanese patients with CD20-positive CLL.

</sec>
<sec>
<title>Clinical trial number</title>
JapicCTI-132285.

</sec>

DOI： 10.1093/jjco/hyaa215

Consolidation with 90 Yttrium-ibritumomab tiuxetan after bendamustine and rituximab for relapsed follicular lymphoma. 国際誌

Katsuhiro Miura, Hideki Tsujimura, Yasufumi Masaki, Masaki Iino, Jun Takizawa, Yoshinobu Maeda, Kazuhiko Yamamoto, Shinobu Tamura, Akiyo Yoshida, Hideo Yagi, Isao Yoshida, Koichi Kitazume, Taro Masunari, Ilseung Choi, Yasutaka Kakinoki, Ritsuro Suzuki, Tadashi Yoshino, Shigeo Nakamura, Yoshihiro Hatta, Takashi Yoshida, Masatoshi Kanno

Hematological oncology 39 ( 1 ) 51 - 59 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Bendamustine and rituximab (BR) are widely used in patients with follicular lymphoma (FL) previously treated with conventional immunochemotherapy, but the role of consolidation radioimmunotherapy in these patients is unknown. This study evaluated the efficacy and safety of consolidation with 90 Yttrium-ibritumomab tiuxetan (90 Y-IT) after re-induction therapy with BR in patients with previously treated FL. This study included adult patients with relapsed FL who had undergone one or two prior therapies. Re-induction therapy with BR was administered every 4 weeks up to 4-6 cycles. If patients achieved at least partial response, 90 Y-IT was administered as consolidation therapy. The primary endpoint was 2-year progression-free survival (PFS) after consolidation. A total of 24 FL patients (median age 60 years) who had undergone one (n = 17) or two (n = 7) prior treatments received BR. After BR therapy, 22 patients proceeded to consolidation with 90 Y-IT, resulting in an overall 88% response rate to the protocol treatment. Within a median observation period of 46.8 months, the estimated 2-year PFS rate after the consolidation among the 22 patients receiving 90 Y-IT was 59% (95% confidence interval [CI], 38%-77%). Patients whose remission after previous treatment had lasted ≥2 years had a significantly higher 2-year PFS rate than patients whose remission after previous treatment had been <2 years (68% vs. 33%, Wilcoxon p = 0.0211). Major adverse events during the protocol treatment and within 2 years after the consolidation were hematological toxicities, but they were generally acceptable. Consequently, the estimated 2-year overall survival after the consolidation was 95% (95% CI, 74%-99%). In conclusion, in a subset of patients with previously treated FL, 90 Y-IT consolidation after BR re-induction conferred a durable remission, indicating that consolidation therapy using 90 Y-IT may be a novel therapeutic option for patients with relapsed FL (UMIN000008793).

DOI： 10.1002/hon.2809

DA-EPOCH-R therapy for high-grade B-cell lymphoma with <i>MYC</i> and <i>BCL2</i> and/or <i>BCL6</i> rearrangements in a patient with renal dysfunction 査読

Masaki Mitobe, Keisuke Kawamoto, Takaharu Suzuki, Tatsuya Suwabe, Yasuhiko Shibasaki, Masayoshi Masuko, Kanako Inoue, Hiroaki Miyoshi, Koichi Ohshima, Hirohito Sone, Jun Takizawa

Journal of Clinical and Experimental Hematopathology 61 ( 1 ) 42 - 47 2021年

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Society for Lymphoreticular Tissue Research

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, also known as double-hit lymphoma, has been reported as refractory to R-CHOP therapy and requires more intensive regimens. However, intensive and safe regimens for patients with renal dysfunction are unknown. Herein, we report the successful use of DA-EPOCH-R therapy for double-hit lymphoma in a 64-year-old man with renal dysfunction. The patient had lymphoma-induced bilateral ureteral obstruction. Although renal dysfunction remained after removing the obstruction using R-CHOP therapy, we completed six cycles of DA-EPOCH-R therapy without any major adverse events. DA-EPOCH-R therapy may be a safe regimen for renal dysfunction patients.

DOI： 10.3960/jslrt.20043

Real World Treatment Practices for Chronic Lymphocytic Leukemia in Japan: An Observational Database Research Study (CLIMBER-DBR)

Jun Takizawa, Koji Izutsu, Hirokazu Nagai, Kenjiro Fukase, Maki Nakamura, Masahisa Jinushi, Junji Suzumiya

Journal of Clinical and Experimental Hematopathology 61 ( 3 ) 126 - 134 2021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：Japanese Society for Lymphoreticular Tissue Research

There are limited real-world data on the treatment practices and healthcare resource utilization associated with chronic lymphocytic leukemia (CLL) in Japan. In this study (CLIMBER-DBR), we performed retrospective analyses of the Japanese Medical Data Vision database, and extracted data for 2562 patients with newly diagnosed CLL (CLL-1 cohort) and 930 patients receiving CLL treatment (CLL-2 cohort) registered between March 1, 2013 and February 28, 2018. The median follow-up in the CLL-1 cohort was 721 (quartile 1-3: 363-1267) days and the median time to initial (first-line) treatment was 1331 (quartile 1-3: 189-not reached) days. In the CLL-2 cohort, the most frequently used regimens were fludarabine alone (17.7%), cyclophosphamide alone (13.7%), and bendamustine/rituximab (8.2%). The median (quartile 1-3) times to second-line and third-line treatments were 1066 (273-not reached) and 1795 (631-not reached) days, respectively. The CLIMBER-DBR was the first database research study to assess current treatment practices for CLL in Japan, where the treatment patterns were driven by the approval/reimbursement status of drugs in the study period. Our study provides an important benchmark for future studies of CLL in Japan.

DOI： 10.3960/jslrt.20044

Real World Treatment Practices for Mantle Cell Lymphoma in Japan: An Observational Database Research Study (CLIMBER-DBR)

Koji Izutsu, Junji Suzumiya, Jun Takizawa, Kenjiro Fukase, Maki Nakamura, Masahisa Jinushi, Hirokazu Nagai

Journal of Clinical and Experimental Hematopathology 61 ( 3 ) 135 - 144 2021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：Japanese Society for Lymphoreticular Tissue Research

Mantle cell lymphoma (MCL) accounts for approximately 3% of all cases of malignant lymphoma in Japan. The CLIMBER-DBR (Treatment practices and patient burden in chronic lymphocytic leukemia and mantle cell lymphoma patients in the real world: An observational database research in Japan) study examined the clinical characteristics, treatment patterns, and health-care resource utilization of MCL in a real-world clinical setting in Japan. Using the Japanese Medical Data Vision database, we extracted data for 1130 patients with MCL (ICD-10 code C83.1) registered between March 1, 2013 and February 28, 2018. The date of first MCL diagnosis was taken as the index date. The mean (standard deviation) age, body weight, and modified Charlson Comorbidity Index were 71.4 (10.9) years, 58.3 (11.7) kg, and 1.9 (1.6). respectively, and 24.6% were <= 65 years old. The median follow-up period was 654 days (first-third quartile 290.5-1049 days). A total of 802 patients (71.0%) underwent first-line treatment. The most common first-line treatment was bendamustine/rituximab (BR; 27.8%), followed by rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP; 15.6%) and rituximab/tetrahydropyranyl-adriamycin/cyclo-phosphamide/vincristine/prednisolone (R-THP-COP; 6.5%). The median (95% confidence interval) times to initial (first-line), second-line, and third-line treatments were 45 (36-62), 687 (624-734), and 1188 (1099-1444) days, respectively. Treatment practices for MCL in Japan are consistent with trends observed in Western countries. Our study can serve as a benchmark to assess future MCL treatments in Japan.

DOI： 10.3960/jslrt.20056

Combination of CD47 and signal‐regulatory protein‐α constituting the “don’t eat me signal” is a prognostic factor in diffuse large B‐cell lymphoma 査読国際誌

Ryo Kazama, Hiroaki Miyoshi, Mai Takeuchi, Kohta Miyawaki, Kazutaka Nakashima, Noriaki Yoshida, Keisuke Kawamoto, Eriko Yanagida, Kyohei Yamada, Takeshi Umeno, Takaharu Suzuki, Koji Kato, Jun Takizawa, Masao Seto, Koichi Akashi, Koichi Ohshima

Cancer Science 111 ( 7 ) 2608 - 2619 2020年7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

The interaction between CD47 and signal-regulatory protein-α (SIRPα) inhibits phagocytosis, thus affecting the clinical outcomes of neoplastic diseases. Although CD47 upregulation is associated with poor prognosis in several malignancies, the effect of SIRPα expression and its coexpression with CD47 remains unclear. This study aimed to investigate the clinicopathologic effect of CD47 and SIRPα expression in diffuse large B-cell lymphoma (DLBCL). Immunostaining of 120 biopsy samples showed that CD47 is primarily expressed in tumor cells, whereas SIRPα is expressed in nonneoplastic stromal cells, mostly macrophages. CD47high cases showed higher MYC protein expression and lower MYC translocation. The SIRPαhigh cases presented significantly shorter overall survival (OS) and progression-free survival (PFS) than SIRPαlow cases in the activated B-cell (ABC) subtype of DLBCL (P = .04 and P = .02, respectively). Both CD47high and SIRPαhigh presented significantly shorter OS and PFS than other cases among all DLBCL patients (P = .01 and P = .004, respectively), and the ABC type (P = .04 and P = .008, respectively) but not the germinal center B-cell type. Both CD47high and SIRPαhigh yielded a constant independent prognostic value for OS and PFS in multivariate analysis (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.20-7.43; P = .02; and HR, 2.87; 95% CI, 1.42-5.85; P = .003, respectively). To the best of our knowledge, this is the first study to report that combinatorial CD47 and SIRPα expression is a potential independent prognostic factor for DLBCL. Evaluation of CD47 and SIRPα expression could be useful before CD47 blockade therapy.

DOI： 10.1111/cas.14437

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14437

Evolution in the management of chronic lymphocytic leukemia in Japan: should MRD negativity be the goal? 査読

Junji Suzumiya, Jun Takizawa

International Journal of Hematology 111 ( 5 ) 642 - 656 2020年5月

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): a multicentre, single-arm, phase 2 trial 査読国際誌

Kazuyuki Shimada, Motoko Yamaguchi, Yoshiko Atsuta, Kosei Matsue, Keijiro Sato, Shigeru Kusumoto, Hirokazu Nagai, Jun Takizawa, Noriko Fukuhara, Koji Nagafuji, Kana Miyazaki, Eiichi Ohtsuka, Masataka Okamoto, Yasumasa Sugita, Toshiki Uchida, Satoshi Kayukawa, Atsushi Wake, Daisuke Ennishi, Yukio Kondo, Tohru Izumi, Yoshihiro Kin, Kunihiro Tsukasaki, Daigo Hashimoto, Masaaki Yuge, Atsumi Yanagisawa, Yachiyo Kuwatsuka, Satoko Shimada, Yasufumi Masaki, Nozomi Niitsu, Hitoshi Kiyoi, Ritsuro Suzuki, Takashi Tokunaga, Shigeo Nakamura, Tomohiro Kinoshita

The Lancet Oncology 21 ( 4 ) 593 - 602 2020年4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：Elsevier BV

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. We aimed to ascertain the safety and activity of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) with high-dose methotrexate and intrathecal chemotherapy as CNS-oriented therapy for patients with previously untreated IVLBCL. METHODS: PRIMEUR-IVL is a multicentre, single-arm, phase 2 trial at 22 hospitals in Japan. Eligible patients had untreated histologically confirmed IVLBCL, were aged 20-79 years, had an Eastern Cooperative Group performance status of 0-3, and had no apparent CNS involvement at diagnosis. Patients received three cycles of R-CHOP (rituximab 375 mg/m2 intravenously on day 1 [except cycle one, which was on day 8]; cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2·0 mg] intravenously on day 1 of cycle one and day 2 of cycles two and three; and prednisolone 100 mg/day orally on days 1-5 of cycle one and days 2-6 of cycles two and three) followed by two cycles of rituximab with high-dose methotrexate (3·5 g/m2 intravenously on day 2 of cycles four and five) every 2 weeks and three additional cycles of R-CHOP. Intrathecal chemotherapy (methotrexate 15 mg, cytarabine 40 mg, and prednisolone 10 mg) was administered four times during the R-CHOP phase. The primary endpoint was 2-year progression-free survival. Efficacy analyses were done in all enrolled patients; safety analyses were done in all enrolled and treated patients. The trial is registered in the UMIN Clinical Trials Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165); the trial is ongoing for long-term follow-up. FINDINGS: Between June 16, 2011, and July 21, 2016, 38 patients were enrolled, of whom 37 were eligible; one patient was excluded because of a history of testicular lymphoma. Median follow-up was 3·9 years (IQR 2·5-5·5). 2-year progression-free survival was 76% (95% CI 58-87). The most frequent adverse events of grade 3-4 were neutropenia and leucocytopenia, which were reported in all 38 (100%) patients. Serious adverse events were hypokalaemia, febrile neutropenia with hypotension, hypertension, and intracerebral haemorrhage (reported in one [3%] patient each). No treatment-related deaths occurred during protocol treatment. INTERPRETATION: R-CHOP combined with rituximab and high-dose methotrexate plus intrathecal chemotherapy is a safe and active treatment for patients with IVLBCL without apparent CNS involvement at diagnosis, and this regimen warrants future investigation. FUNDING: The Japan Agency for Medical Research and Development, the Center for Supporting Hematology-Oncology Trials, and the National Cancer Center.

DOI： 10.1016/s1470-2045(20)30059-0

Clinicopathological analysis of splenic red pulp low-grade B-cell lymphoma. 査読国際誌

Takaharu Suzuki, Hiroaki Miyoshi, Joji Shimono, Keisuke Kawamoto, Fumiko Arakawa, Takuya Furuta, Kyohei Yamada, Eriko Yanagida, Mai Takeuchi, Masao Seto, Hirohito Sone, Jun Takizawa, Koichi Ohshima

Pathology international 70 ( 5 ) 280 - 286 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Primary splenic low-grade B-cell lymphoma of the red pulp comprises hairy cell leukemia (HCL) and splenic B-cell lymphoma/leukemia, unclassifiable (SPLL-U). SPLL-U is a rare disease that includes subtypes of a hairy cell leukemia-variant (HCL-v), splenic diffuse red pulp small B-cell lymphoma (SDRPL) and other types that are known as narrow sense SPLL-U (SPLL-U-NS). Notably, limited information is available regarding the BRAF mutation (V600E) and cyclin D3 expression in subtypes of SPLL-U. Therefore, we performed a pathological analysis of the BRAF mutation (V600E) and characterized pathological features of SPLL-U. We reviewed the pathological findings of 12 SPLL-U cases. The 12 cases considered included two cases of HCL-v, six cases of SPLL-U-NS and four undetermined cases. The BRAF mutation (V600E) was detected in three cases, which were all SPLL-U-NS. Cases with the BRAF mutation (V600E) have increased levels of CD103 expression and decreased cyclin D3 and cyclin D1 expression compared with cases that lacked the BRAF mutation. These findings suggest that the BRAF mutation might play a significant role in SPLL-U. Therefore, the significance of the BRAF mutation should be evaluated via genomic or transcriptional analyses of a large cohort of SPLL-U patients.

DOI： 10.1111/pin.12909

The natural course of IgG4-related ophthalmic disease after debulking surgery: a single-centre retrospective study 査読国際誌

Jun Ominato, Tokuhide Oyama, Hiroyuki Cho, Naoya Shiozaki, Hajime Umezu, Jun Takizawa, Takeo Fukuchi

BMJ Open Ophthalmology 4 ( 1 ) e000295 - e000295 2019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：BMJ

<sec><title>Objective</title>This study aimed to examine the natural course and relapse rate of IgG4-related ophthalmic disease (IgG4-ROD) after debulking surgery in Japanese patients.

</sec><sec><title>Methods and analysis</title>This retrospective review included patients with IgG4-ROD who did not undergo further treatment following debulking surgery. The patients were diagnosed between January 2009 and December 2018 at the Department of Ophthalmology and Pathology, Niigata University Medical and Dental Hospital. The main outcome measures included postoperative IgG4-ROD recurrence rate and differences between patients with and without recurrent disease.

</sec><sec><title>Results</title>Fifteen patients (six male, 9 female; 61.8±16.2 years) were included. Twelve patients (80.0%) had dacryoadenitis disease and three patients (20.0%) had orbital fat tissue disease. About 70%–100% of the lesion was resected in the debulking surgery and the pathological diagnosis was rendered. A definitive diagnosis was made in 13 cases (86.7%) and a probable diagnosis in 2 cases (13.3%). Patients were followed up for 39.0±25.5 months following operation. All patients had lesion volume reduction and patients with dacryoadenitis had eyelid swelling improvement after surgery. Two patients (13.3%) had disease recurrence and six patients (40.0%) had extraophthalmic lesions. There was no statistically significant difference in clinical features between relapsed and non-recurring cases.

</sec><sec><title>Conclusion</title>We observed a 13.3% relapse rate following debulking surgery in patients with IgG4-ROD who did not undergo further treatment. This rate is lower than the documented relapse rate of 30%–70% following oral prednisolone therapy. Therefore, debulking surgery may be a treatment option for IgG4-ROD.

</sec>

DOI： 10.1136/bmjophth-2019-000295

Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin. 査読国際誌

Yamaguchi M, Suzuki R, Miyazaki K, Amaki J, Takizawa J, Sekiguchi N, Kinoshita S, Tomita N, Wada H, Kobayashi Y, Niitsu N, Ando T, Maeda T, Saito B, Matsuoka H, Sakai R, Kubota N, Masaki Y, Kameoka Y, Asano N, Oguchi M, Katayama N

Annals of hematology 98 ( 7 ) 1647 - 1655 2019年7月

Memory B cell pool of autoimmune pulmonary alveolar proteinosis patients contains higher frequency of GM-CSF autoreactive B cells than healthy subjects. 査読国際誌

Nei T, Urano S, Motoi N, Hashimoto A, Kitamura N, Tanaka T, Nakagaki K, Takizawa J, Kaneko C, Tazawa R, Nakata K

Immunology Letters 212 22 - 29 2019年6月

Safety and effective salvage regimen comprising a novel combination of brentuximab vedotin, L-asparaginase, and dexamethasone for refractory anaplastic large cell lymphoma, anaplastic lymphoma kinase negative. 査読国際誌

Kawamoto K, Suzuki T, Kasami T, Kiryu M, Sone H, Miyoshi H, Ohshima K, Takizawa J

Hematological oncology 37 ( 2 ) 212 - 214 2019年4月

Gemcitabine, Dexamethasone, and Cisplatin Regimen as an Effective Salvage Therapy for High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements. 査読

Mitobe M, Kawamoto K, Suzuki T, Kiryu M, Tamura S, Nanba A, Suwabe T, Tanaka T, Fuse K, Shibasaki Y, Masuko M, Miyoshi H, Ohshima K, Sone H, Takizawa J

Internal medicine (Tokyo, Japan) 58 ( 4 ) 575 - 580 2019年2月

Anaplastic large cell lymphoma, with 1,25(OH)<sub><sup>2</sup></sub>D<sub><sup>3</sup></sub>-mediated hypercalcemia: A case report. 査読

Mitobe M, Kawamoto K, Suzuki T, Kiryu M, Nanba A, Suwabe T, Tanaka T, Fuse K, Shibasaki Y, Masuko M, Miyoshi H, Ohshima K, Sone H, Takizawa J

Journal of clinical and experimental hematopathology : JCEH 59 ( 1 ) 22 - 28 2019年

Cladribine treatment for Erdheim-Chester disease involving the central nervous system and concomitant polycythemia vera: A case report. 査読

Tamura S, Kawamoto K, Miyoshi H, Suzuki T, Katagiri T, Kasami T, Nemoto H, Miyakoshi S, Kobayashi H, Shibasaki Y, Masuko M, Takeuchi K, Ohshima K, Sone H, Takizawa J

Journal of clinical and experimental hematopathology : JCEH 58 ( 4 ) 161 - 165 2018年12月

Identification of the BRAF V600E mutation in Japanese patients with hairy cell leukemia and related diseases using a quenching probe method. 査読

Itamura H, Ide M, Sato A, Sueoka-Aragane N, Sueoka E, Nishida A, Masunari T, Aoki S, Takizawa J, Suzumiya J, Kimura S

International journal of hematology 108 ( 4 ) 416 - 422 2018年10月

A distinct subtype of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorder: adult patients with chronic active Epstein-Barr virus infection-like features. 査読国際誌

Keisuke Kawamoto, Hiroaki Miyoshi, Takaharu Suzuki, Yasuji Kozai, Koji Kato, Masaharu Miyahara, Toshiaki Yujiri, Ilseung Choi, Katsumichi Fujimaki, Tsuyoshi Muta, Masaaki Kume, Sayaka Moriguchi, Shinobu Tamura, Takeharu Kato, Hiroyuki Tagawa, Junya Makiyama, Yuji Kanisawa, Yuya Sasaki, Daisuke Kurita, Kyohei Yamada, Joji Shimono, Hirohito Sone, Jun Takizawa, Masao Seto, Hiroshi Kimura, Koichi Ohshima

Haematologica 103 ( 6 ) 1018 - 1028 2018年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (P=0.005), but greater frequency of skin lesions (P<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (P<0.001 and P=0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P=0.0087, P=0.0236, and P=0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (P<0.001 and P=0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.

DOI： 10.3324/haematol.2017.174177

Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response 査読国際誌

Sakamoto K, Katayama R, Asaka R, Sakata S, Baba S, Nakasone H, Koike S, Tsuyama N, Dobashi A, Sasaki M, Ichinohasama R, Takakuwa E, Yamazaki R, Takizawa J, Maeda T, Narita M, Izutsu K, Kanda Y, Ohshima K, Takeuchi K

Leukemia 32 ( 12 ) 2590 - 2603 2018年5月

Expression of programmed death ligand 1 is associated with poor prognosis in myeloid sarcoma patients. 査読国際誌

Kawamoto K, Miyoshi H, Suzuki T, Kiyasu J, Yokoyama S, Sasaki Y, Sone H, Seto M, Takizawa J, Ohshima K

Hematol Oncol. 36 ( 3 ) 591 - 599 2018年3月

MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia. 査読

Kozakai T, Takahashi M, Higuchi M, Hara T, Saito K, Tanaka Y, Masuko M, Takizawa J, Sone H, Fujii M

International journal of hematology 107 ( 3 ) 337 - 344 2018年3月

Clinicopathological and genomic analysis of double-hit follicular lymphoma: Comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements 査読

Masashi Miyaoka, Yara Y. Kikuti, Joaquim Carreras, Haruka Ikoma, Shinichiro Hiraiwa, Akifumi Ichiki, Minoru Kojima, Kiyoshi Ando, Tomoyuki Yokose, Rika Sakai, Masahiro Hoshikawa, Naoto Tomita, Ikuo Miura, Katsuyoshi Takata, Tadashi Yoshino, Jun Takizawa, Silvia Bea, Elias Campo, Naoya Nakamura

Modern Pathology 31 ( 2 ) 313 - 326 2018年2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：Nature Publishing Group

Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48-82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1-132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (Po0.05). In comparison with highgrade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements, double-hit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus also significant against conventional follicular lymphomas (P=0.0001). In summary, double-hit follicular lymphomas tended to be high-grade histology, high MYC protein expression, high MYC/IGH fusion, and minimal common region of gain at 2p16.1. Double-hit follicular lymphomas seemed to be a different disease from high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements and have an indolent clinical behavior similar to follicular lymphomas without MYC rearrangement.

DOI： 10.1038/modpathol.2017.134

Frequent expression of CD30 in extranodal NK/T-cell lymphoma: Potential therapeutic target for anti-CD30 antibody-based therapy. 査読国際誌

Keisuke Kawamoto, Hiroaki Miyoshi, Takaharu Suzuki, Yuya Sasaki, Kyohei Yamada, Eriko Yanagida, Reiji Muto, Maiko Kiryu, Hirohito Sone, Masao Seto, Koichi Ohshima, Jun Takizawa

Hematological oncology 36 ( 1 ) 166 - 173 2018年2月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is a subtype of non-Hodgkin lymphoma with a poor prognosis. Although first-line treatments for patients with localized ENKTL have been established, there is no gold standard treatment for patients with advanced ENKTL and refractory and/or relapsed disease. Anti-CD30 antibody-based therapy, including brentuximab vedotin (BV), has been shown to target malignant lymphomas with CD30 expression. In particular, this therapeutic agent has recently been suggested to be effective for Hodgkin lymphoma and mature T-cell lymphoma. However, the efficacy of BV toward ENKTL has not yet been established. Therefore, we investigated the expression of CD30 in a large cohort to evaluate BV as a potential treatment for ENKTL. In this study, 97 Japanese patients with newly diagnosed ENKTL between January 2007 and December 2015 were enrolled. Flow cytometry and immunohistochemistry were performed for the evaluation of CD30 expression. If the cut-off value of CD30 expression is 1% or more, there were 55 positive cases (56.5%). According to the localization of lesion, the frequency of CD30 expression was significantly higher in the non-nasal type than in the nasal type (P = .0394). No differences were observed in almost all clinical characteristics between CD30-positive cases and CD30-negative cases. In addition, the expression of CD30 was not a prognostic factor for either overall survival or progression-free survival. In conclusion, frequent expression of CD30 in ENKTL suggests anti-CD30 antibody-based therapy may be an effective treatment.

DOI： 10.1002/hon.2482

Improved Prognosis of Extranodal NK/T-Cell Lymphoma, Nasal Type (ENKL) of Nasal Origin but Not Extranasal Origin: An Analysis of NKEA Study 査読

Yamaguchi Motoko, Suzuki Ritsuro, Miyazaki Kana, Amaki Jun, Takizawa Jun, Sekiguchi Nodoka, Inagaki Shiori, Tomita Naoto, Wada Hideho, Kobayashi Yukio, Niitsu Nozomi, Ando Toshihiko, Maeda Takeshi, Saito Bungo, Matsuoka Hiroshi, Sakai Rika, Kubota Nobuko, Masaki Yasufumi, Asano Naoko, Oguchi Masahiko, Katayama Naoyuki

BLOOD 130 2017年12月

Successful 5-azacytidine treatment of myeloid sarcoma and leukemia cutis associated with myelodysplastic syndrome A case report and literature review 査読

Takayuki Katagiri, Takashi Ushiki, Masayoshi Masuko, Tomoyuki Tanaka, Shukuko Miyakoshi, Kyoko Fuse, Yasuhiko Shibasaki, Jun Takizawa, Sadao Aoki, Hirohito Sone

MEDICINE 96 ( 36 ) e7975 2017年9月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Rationale: Myeloid sarcoma (MS) and leukemia cutis (LC) are extramedullary tumors comprising myeloid blasts. They can occur de novo or concurrently with hematological disorders, usually acute myeloid leukemia (AML). AML chemotherapy is generally the initial therapy for MS and LC, and hematopoietic stem cell transplantation (HSCT) can be considered as additional therapy. However, treatment for older patients who are unable to continue intensive chemotherapy is not currently standardized.
Patientconcerns: A 71-year-old Japanese woman was diagnosed with multiple MSs associated with myelodysplastic syndrome (MDS), using bone marrow aspiration and lymph node biopsy.
Diagnoses: Additionally, LC was diagnosed by skin biopsy. Extramedullary MS and LC lesions were formed by massive infiltration of myeloblastic cells.
Interventions: Twenty courses of 5-azacytidine (5-Aza) were administrated as maintenance therapy after induction therapy with daunorubicin and cytarabine.
Outcomes: Myeloblasts decreased in the bone marrow and the LC disappeared after induction therapy. The MSs completely disappeared, except for the palatine tonsil lesion, after 5-Aza maintenance therapy. 5-Aza treatment provided long-term partial response for more than 21 months.
Lessons: 5-Aza was well tolerated and may be a good option for the treatment of MS and LC associated with MDS, especially in older patients who cannot receive HSCT.

DOI： 10.1097/MD.0000000000007975

Clinicopathological features of cryptococcal lymphadenitis and a review of literature. 査読

Kawamoto K, Miyoshi H, Suzuki T, Muto R, Yamada K, Yanagida E, Koshino M, Sasaki Y, Takizawa J, Sone H, Sugita Y, Seto M, Ohshima K

Journal of clinical and experimental hematopathology : JCEH 57 ( 1 ) 26 - 30 2017年7月

Comparison of clinicopathological characteristics between T-cell prolymphocytic leukemia and peripheral T-cell lymphoma, not otherwise specified 査読

Keisuke Kawamoto, Hiroaki Miyoshi, Eriko Yanagida, Noriaki Yoshida, Junichi Kiyasu, Yasuji Kozai, Tatsuma Morikita, Takeharu Kato, Hitoshi Suzushima, Shinobu Tamura, Tsuyoshi Muta, Koji Kato, Tetsuya Eto, Ritsuko Seki, Koji Nagafuji, Hirohito Sone, Jun Takizawa, Masao Seto, Koichi Ohshima

EUROPEAN JOURNAL OF HAEMATOLOGY 98 ( 5 ) 459 - 466 2017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

ObjectivesT-cell prolymphocytic leukemia (T-PLL) is a very rare, aggressive T-cell neoplasm. Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is also a highly aggressive lymphoma. These two diseases can often be confused with each other; therefore, we aimed to determine the clinical and pathological differences between T-PLL and PTCL-NOS.
MethodsWe analyzed 15 T-PLL and 91 PTCL-NOS patients and also compared clinical features between T-PLL and PTCL-NOS with leukemic presentation. Peripheral blood images and biopsy specimens were analyzed, and treatment responses were determined via imaging modalities. The clinicopathological characteristics were statistically compared.
ResultsT-PLL cells were smaller in size than those of PTCL-NOS with leukemic presentation (P=.0068); moreover, PTCL-NOS cells with leukemic presentation were smaller than those of PTCL-NOS without leukemic presentation (P=.0017). Immunophenotypic patterns in T-PLL and PTCL-NOS were similar. Five-year overall survival rates of T-PLL and all PTCL-NOS patients were 57.5% and 36.8%, respectively. No significant differences were found in clinical manifestations or prognoses; T-PLL and PTCL-NOS with leukemic presentation had essentially equivalent characteristics.
ConclusionT-PLL and PTCL-NOS may share common biological and clinical characteristics in Japanese patients.

DOI： 10.1111/ejh.12856

Treatments and Outcomes of Patients With Extranodal Natural Killer/T-Cell Lymphoma Diagnosed Between 2000 and 2013: A Cooperative Study in Japan 査読

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

JOURNAL OF CLINICAL ONCOLOGY 35 ( 1 ) 32 - + 2017年1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 CLINICAL ONCOLOGY

Purpose
To elucidate the management and outcomes of patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKL), who were diagnosed between 2000 and 2013 in Japan.
Patients and Methods
Data from 358 patients with ENKL diagnosed between 2000 and 2013 from 31 institutes were retrospectively analyzed.
Results
Patients' median age was 58 years, and 257 (72%) had localized disease. The most common first-line treatment was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%) for localized ENKL and L-asparaginase-containing chemotherapy (30%) for advanced ENKL. With a median follow-up of 5.8 years, overall survival (OS) rates at 5 years for localized and advanced ENKL were 68% and 24%, respectively. The prognostic index of natural killer lymphoma was validated in our study, although only 4% of patients with localized ENKL were classified as high risk. With a median follow-up of 5.6 years, OS and progression-free survival at 5 years in the 150 patients who received RT-DeVIC in clinical practice were 72% (95% CI, 63% to 78%) and 61% (95% CI, 52% to 69%), respectively. Toxicities of RT-DeVIC were comparable to those in a previous trial. Multivariate analysis in patients with localized ENKL who received RT-DeVIC identified elevated soluble interleukin-2 receptor as an independent predictive factor for worse OS and progression-free survival (adjusted hazard ratios, 2.28 and 2.46; 95% CI, 1.24 to 4.23 and 1.42 to 4.28; P = .008 and .0014, respectively).
Conclusion
Favorable OS in response to new treatments was demonstrated in a large number of patients. Improved treatment approaches are needed for localized ENKL exhibiting elevated pretreatment soluble interleukin-2 receptor. (C) 2016 by American Society of Clinical Oncology

DOI： 10.1200/JCO.2016.68.1619

A Host-Dependent Prognostic Model for Elderly Patients with Diffuse Large B-Cell Lymphoma 査読

Katsuhiro Miura, Jun Konishi, Takaaki Miyake, Masanori Makita, Atsuko Hojo, Yasufumi Masaki, Masatoshi Uno, Jun Ozaki, Chikamasa Yoshida, Daigo Niiya, Koichi Kitazume, Yoshinobu Maeda, Jun Takizawa, Rika Sakai, Tomofumi Yano, Kazuhiko Yamamoto, Kazutaka Sunami, Yasushi Hiramatsu, Kazutoshi Aoyama, Hideki Tsujimura, Jun Murakami, Yoshihiro Hatta, Masatoshi Kanno

ONCOLOGIST 22 ( 5 ) 554 - 560 2017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：WILEY

Background. Decision-making models for elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) are in great demand.
Patients and Methods. The Society of Lymphoma Treatment in Japan (SoLT-J), in collaboration with the West-Japan Hematology and Oncology Group (West-JHOG), collected and retrospectively analyzed the clinical records of >= 65-year-old patients with DLBCL treated with R-CHOP from 19 sites across Japan to build an algorithm that can stratify adherence to R-CHOP.
Results. A total of 836 patients with a median age of 74 years ( range, 65-96 years) were analyzed. In the SoLT-J cohort (n=555), age >75 years, serum albumin level <3.7 g/dL, and Charlson Comorbidity Index score >= 3 were independent adverse risk factors and were defined as the Age, Comorbidities, and Albumin (ACA) index. Based on their ACA index score, patients were categorized into "excellent" (0 points), "good" (1 point), "moderate" (2 points), and "poor" (3 points) groups. This grouping effectively discriminated the 3-year overall survival rates, mean relative total doses (or relative dose intensity) of anthracycline and cyclophosphamide, unanticipated R-CHOP discontinuance rates, febrile neutropenia rates, and treatment-related death rates. Additionally, the ACA index showed comparable results for these clinical parameters when it was applied to the West-JHOG cohort (n5281).
Conclusion. The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP.

DOI： 10.1634/theoncologist.2016-0260

Successful umbilical cord blood hematopoietic stem cell transplantation in a patient with adult T-cell leukemia/lymphoma initially achieving complete remission with anti-CC chemokine receptor 4 antibody combined chemotherapy. 査読

Suwabe T, Shibasaki Y, Kaihatsu A, Katagiri T, Miyakoshi S, Fuse K, Kobayashi H, Ushiki T, Moriyama M, Takizawa J, Narita M, Sone H, Masuko M

[Rinsho ketsueki] The Japanese journal of clinical hematology 58 ( 1 ) 32 - 36 2017年

The SIL index is a simple and objective prognostic indicator in diffuse large B-cell lymphoma 査読

Naoto Tomita, Taisei Suzuki, Kazuho Miyashita, Wataru Yamamoto, Kenji Motohashi, Takayoshi Tachibana, Hirotaka Takasaki, Rika Kawasaki, Maki Hagihara, Chizuko Hashimoto, Sachiya Takemura, Hideyuki Koharazawa, Etsuko Yamazaki, Jun Taguchi, Katsumichi Fujimaki, Hiroyuki Fujita, Rika Sakai, Shin Fujisawa, Shigeki Motomura, Keisuke Kawamoto, Hirohito Sone, Jun Takizawa

LEUKEMIA & LYMPHOMA 57 ( 12 ) 2763 - 2770 2016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：TAYLOR & FRANCIS LTD

We previously developed a prognostic index, SIL, which includes advanced stage (5), soluble interleukin-2 receptor level (I), and elevated lactate dehydrogenase level (L) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone (R-CHOP). This time we evaluated the index in a larger cohort and its utility in the risk stratification. The above three factors were independent risk of progression-free survival (PFS). Five-year PFS rates in the standard-risk (SIL index: 0 or 1, n = 367) and high-risk groups (SIL index: 2 or 3, n = 205) were 79% and 53%, respectively (p < 0.0001). When the patients were divided by age (<= 60 years and >60 years), the SIL index was a good prognostic indicator for PFS in both groups as well as divided by the number of extranodal involvement site (0-1 and >1). The SIL index is a simple and objective prognostic indicator in DLBCL.

DOI： 10.1080/10428194.2016.1195498

Clinicopathological, Cytogenetic, and Prognostic Analysis of 131 Myeloid Sarcoma Patients 査読

Keisuke Kawamoto, Hiroaki Miyoshi, Noriaki Yoshida, Jun Takizawa, Hirohito Sone, Koichi Ohshima

AMERICAN JOURNAL OF SURGICAL PATHOLOGY 40 ( 11 ) 1473 - 1483 2016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：LIPPINCOTT WILLIAMS & WILKINS

Myeloid sarcoma (MS) is an extramedullary tumor of immature myeloid cells. We analyzed 131 patients with MS, including: (1) de novo MS; (2) MS with concomitant acute myeloid leukemia (AML); (3) MS following myelodysplastic syndrome, myeloproliferative neoplasm, or chronic myelogenous leukemia; and (4) MS as a recurrence of AML. The most common development site was the lymph node. Testicular lesions were statistically more frequent in MS as a recurrence of AML than in other types of MS (P = 0.0183). MS tended to lack myeloid markers (myeloperoxidase was present in 63.2%, CD68 in 51.3%, CD13 in 48.7%, and CD33 in 48.7% of patients) and express T-cell markers such as CD3 (20.7%) and CD5 (34.2%). All T-cell marker-positive MS cases were negative for the alpha beta and gamma delta T-cell receptors on immunohistochemistry. Underlying myelodysplastic syndrome or myeloproliferative neoplasm was a poor prognostic factor (vs. de novo MS: P = 0.0383; vs. MS with concomitant AML: P = 0.0143). However, there was no statistical difference in prognosis between de novo MS and MS with concomitant AML (P = 0.288). There were no significant differences in prognosis between the prognoses of T-cell marker-positive and T-cell marker-negative MS cases. In addition, CXCR4 expression was a poor prognostic factor in MS (P = 0.0229). This study involves the largest MS cohort to date and expands the clinical and pathologic knowledge of the disease.

DOI： 10.1097/PAS.0000000000000727

MYC translocation and/or BCL 2 protein expression are associated with poor prognosis in diffuse large B-cell lymphoma 査読

Keisuke Kawamoto, Hiroaki Miyoshi, Noriaki Yoshida, Naoya Nakamura, Koichi Ohshima, Hirohito Sone, Jun Takizawa

CANCER SCIENCE 107 ( 6 ) 853 - 861 2016年6月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-BLACKWELL

Genomic alterations and protein expression levels have been established as prognostic factors for survival in patients with diffuse large B-cell lymphoma (DLBCL). In particular, double-hit DLBCL (DHL), which exhibits translocations in MYC and BCL2 and/or BCL6, is known to be associated with a poor prognosis. However, the clinical significance of gene alterations and protein expression levels for MYC, B-cell lymphoma (BCL)2, and BCL6 are unclear. In this study, we analyzed 61 adult patients diagnosed with DLBCL without DHL, who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone, or similar regimens. There were no differences in the distribution of MYC expression rates among the different MYC gene statuses. In log-rank tests, MYC translocation was a prognostic factor for overall survival (OS; P = 0.011), whereas BCL2 and BCL6 translocation were not prognostic indicators (P = 0.999 and P = 0.925, respectively). Although the expression levels of MYC and BCL6 were not significantly associated with OS, the expression of BCL2 was a prognostic factor for OS (P = 0.027). Furthermore, copy number gains in the MYC, BCL2, and BCL6 genes did not affect OS. MYC translocation (hazard ratio, 4.769; range, 1.518-14.98; P = 0.007) and BCL2 protein expression (hazard ratio, 3.072; range, 1.002-9.413; P = 0.049) were independent prognostic factors for survival in multivariate analyses. In conclusion, MYC translocation and BCL2 expression may need to be investigated at the initial diagnosis to predict prognosis in patients with DLBCL.

DOI： 10.1111/cas.12942

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

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

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

Pharmacokinetic and pharmacodynamic analysis of cyclosporine A (CsA) to find the best single timepoint for the monitoring and adjusting of CsA dose using twice-daily 3-h intravenous infusions in allogeneic hematopoietic stem cell transplantation. 査読

Furukawa T, Kurasaki-Ida T, Masuko M, Tsukada N, Okazuka K, Sato N, Yano T, Abe T, Momoi A, Shibasaki Y, Higashimura M, Karimata K, Moriyama M, Kuroha T, Takizawa J, Toba K, Narita M, Fuse I, Takahashi M, Aizawa Y

Int J Hematol. 92 ( 1 ) 144 - 151 2010年7月

Proteomic characterization of primary diffuse large B-cell lymphomas in the central nervous system - Laboratory investigation 査読

Jie Li, Hiroaki Okamoto, Chunyue Yin, Jay Jagannathan, Jun Takizawa, Sadao Aoki, Sven Glaesker, Elisabeth J. Rushing, Alexander O. Vortmeyer, Edward H. Oldfield, Ryuya Yamanaka, Zhengping Zhuang

JOURNAL OF NEUROSURGERY 109 ( 3 ) 536 - 546 2008年9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 NEUROLOGICAL SURGEONS

Object. The lack of primary lymphoid tissue within the central nervous system (CNS) confounds our understanding of the pathogenesis of primary CNS lymphomas (PCNSLs). Comparing the protein expression of PCNSLs and sporadic systemic lymphomas (SSLs) provides a useful strategy for identifying a molecular signature that characterizes disease-associated features and provides information regarding tumor initiation and progression.
Methods. Seven diffuse large B-cell PCNSLs were selected to undergo 2D gel electrophoresis, and profiled proteomes from these PCNSLs were compared with those from 7 diffuse large B-cell SSLs. Distinguishing proteins were sequenced using mass spectrometry.
Results. Two-dimensional get electrophoresis identified an average of 706 proteins from each specimen. Computerized gel analysis and manual reconfirmation revealed a 96% similarity in the proteomes of PCNSLs and SSLs. Comparative analysis identified 9 proteins significantly overexpressed (p < 0.05) and 16 proteins downregulated in PCNSLs. The proteomic findings were further validated using Western blot and immunohistochemical staining.
Conclusions. The similarities in proteomic patterns between PCNSLs and SSLs suggest that these tumor types share structural similarities, acquired during differentiation. The ultimate fate of lymphomatous cells (CNS vs systemic) may be related to differentially expressed proteins, which function in homing and host processing. Elucidating the roles of these differentially expressed proteins will prove valuable in understanding the pathogenesis of PCNSL.

DOI： 10.3171/JNS/2008/109/9/0536

Anti-tumor cytotoxicity of gamma delta T cells expanded from peripheral blood cells of patients with myeloma and lymphoma 査読

Anri Saitoh, Miwako Narita, Norihiro Watanabe, Nozomi Tochiki, Noriyuki Satoh, Jun Takizawa, Tatsuo Furukawa, Ken Toba, Yoshifusa Aizawa, Shohji Shinada, Masuhiro Takahashi

MEDICAL ONCOLOGY 25 ( 2 ) 137 - 147 2008年6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：HUMANA PRESS INC

In order to establish an efficient gamma delta T cell-mediated immunotherapy for hematological malignancies, we attempted to evaluate cytotoxicity against tumor cells by gamma delta T cells, which were generated from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and a low dose of IL-2. Although gamma delta T cells were expanded in patients with myeloma and lymphoma as well as normal persons, the amplification rates of gamma delta T cells before and after culturing varied from patient to patient in myeloma and lymphoma. gamma delta T cells generated in patients with myeloma and lymphoma showed a potent cytotoxic ability against myeloma/lymphoma cell lines as shown in gamma delta T cells generated in normal subjects. In addition, gamma delta T cells generated in a patient with myeloma showed a cytotoxic ability against self myeloma cells freshly prepared from bone marrow. However, the same gamma delta T cells were demonstrated to be non-cytotoxic to normal cells of the patient. These data demonstrated that gamma delta T cells, which could be expanded in vitro from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and IL-2, possess a sufficient cytotoxic ability against tumor cells. These findings suggested that in vitro generated patients' gamma delta T cells could be applied to gamma delta T cell-mediated immunotherapy for hematological malignancies.

DOI： 10.1007/s12032-007-9004-4

Successful treatment of adult T-cell leukemia with unrelated cord blood transplantation 査読

Jun Takizawa, Sadao Aoki, Tori Kurasaki, Masutaka Higashimura, Keiichiro Honma, Toshiki Kitajima, Akihito Momoi, Hidenobu Takahashi, Naoya Nakamura, Tatsuo Furukawa, Yoshifusa Aizawal

AMERICAN JOURNAL OF HEMATOLOGY 82 ( 12 ) 1113 - 1115 2007年12月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

This study reports the first well-documented case of adult T-cell leukemia (ATL) successfully treated with unrelated cord blood transplantation (UCBT). A 49-year-old woman was diagnosed with acute-type of ATL. Chemotherapy induced complete remission, but the human T-cell leukemia virus type 1 (HTLV-1) proviral load was detected in mononuclear cells of her peripheral blood. The patient received UCBT with a conditioning regimen consisting of total body irradiation, cytarabine, and cyclophosphamide. She remains in remission 30 months after UCBT and the HTLV-1 proviral load has fallen to undetectable levels. This result suggests that UCBT should be a therapeutic option for ATL patients who do not have suitable donors and those who urgently require treatment. Am. J. Hematol. 82:1113-1115, 2007. (c) 2007 Wiley-Liss, Inc.

DOI： 10.1002/ajh.21042

Enhancement of anti-tumor cytotoxicity of expanded gammadelta T Cells by stimulation with monocyte-derived dendritic cells. 査読

Saito A, Narita M, Yokoyama A, Watanabe N, Tochiki N, Satoh N, Takizawa J, Furukawa T, Toba K, Fuse I, Aizawa Y, Shinada S, Takahashi M

J Clin Exp Hematop. 47 ( 2 ) 61 - 72 2007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 for Lymphoreticular Tissue Research

In order to establish the method of generating powerful γδ T cells for anti-tumor immunotherapy, we investigated the effects of monocyte-derived dendritic cells (mo-DCs) on anti-tumor cytotoxicity of expanded γδ T cells. Activation of γδ T cells co-cultured for 2-3 days with immature or mature mo-DCs was evaluated by CD69 expression and anti-tumor cytotoxicity using two assays : the 5- (and 6-) carboxyfluorescein diacetate, succinimidyl ester-based cytotoxicity assay and the calcein-AM-based Terascan assay. γδ T cells were used as effector cells and myeloma cell line (RPMI8226) or chronic myelogenous leukemia blastic crisis cell line (C2F8) were used as target cells. CD69 expression on γδ T cells was enhanced by co-culture with both immature and mature mo-DCs in a cell-number-dependent fashion. CD69 expression was enhanced after addition of mo-DCs of either autologous or allogeneic origin. Activation of γδ T cells with mo-DCs enhanced anti-tumor cytotoxicity of γδ T cells against RPMI8226 and C2F8 in an effector-to-target ratio-dependent manner. Activation of γδ T cells by mo-DCs was associated with the enhancement of anti-tumor cytotoxicity of γδ T cells. Potent γδ T cells activated by mo-DCs were considered to be applicable to an efficient γδ T cell-mediated immunotherapy for tumors. [<I>J Clin Exp Hematopathol 47(2) </I><I>: 61</I>-<I>72, 2007</I>]

DOI： 10.3960/jslrt.47.61

その他リンク： http://search.jamas.or.jp/link/ui/2008186007

Identification of an overexpressed gene, HSPA4L, the product of which can provoke prevalent humoral immune responses in leukemia patients 査読

Hidenobu Takahashi, Tatsuo Furukawa, Toshio Yano, Naoko Sato, Jun Takizawa, Tori Kurasaki, Takashi Abe, Miwako Narita, Masayoshi Masuko, Satoru Koyama, Ken Toba, Masuhiro Takahashi, Yoshifusa Aizawa

EXPERIMENTAL HEMATOLOGY 35 ( 7 ) 1091 - 1099 2007年7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：ELSEVIER SCIENCE INC

Objective. To identify leukemia-associated antigens, we applied the serological identification of antigens by the recombinant expression cloning (SEREX) method to a chronic myelogenous leukemia (CML) patient who achieved a cytogenetic response to interferon-alpha.
Materials and Methods. Immunoscreening of the cDNA library was performed with sera from a CML patient. Two isolated antigens were used to evaluate the expression pattern using Northern blot analysis and quantitative reverse transcriptase polymerase chain reaction. Western blotting and enzyme-linked immunosorbent assay were also performed for serological analysis.
Results. We identified 14 positive clones, representing five different antigens. Of these, two genes were further validated. One (clone 70) was the human polyribonucleotide nucleotidyltransferase 1 (PNPT1), which is the type I interferon (alpha/beta-responsive gene). The mRNA of clone 70 was ubiquitously expressed in normal human tissues. The other gene (clone 57) was the heat shock 70-kDa protein 4-like (HSPA4L), which is a member of the heat shock protein 110 family, whose mRNA is strongly expressed in normal human testis and overexpressed in leukemia cells. Seroactivity against HSPA4L was detected in 6 of 9 acute myeloid leukemia patients, 4 of 10 acute lymphoblastic leukemia patients, 9 of 11 CML patients, and none of 10 healthy volunteers. Leukemia patients had higher titer of the antibodies against the protein than healthy volunteers.
Conclusions. These results suggest that HSPA4L, a member of heat shock protein, is highly expressed by leukemia cells, and elicit humoral immune responses in leukemia patients, and it might be a potential target for antileukemia therapy and an antigen-specific immunotherapy for leukemia.

DOI： 10.1016/j.exphem.2007.03.015

Plasma brain natriuretic peptide during myeloablative stem cell transplantation. 査読

Masuko M, Ito M, Kurasaki T, Yano T, Takizawa J, Toba K, Aoki S, Fuse I, Kodama M, Furukawa T, Aizawa Y

Internal medicine (Tokyo, Japan) 46 ( 9 ) 551 - 555 2007年

記述言語：英語出版者・発行元：The Japanese Society of Internal Medicine

<b>Objective:</b> Cardiovascular complication is one of the serious complications in stem cell transplantation (SCT). We measured plasma brain natriuretic peptide (BNP) concentrations in patients who received SCT to evaluate possible cardiac toxicity of the regimens employed in SCT.<br> <b>Patients:</b> Ten patients with allogeneic SCT and 5 patients with autologous SCT using myeloablative conditioning regimens were enrolled. The preparative chemotherapy for 8 patients with allogeneic SCT included cyclophosphamide (60 mg/kg i.v. for 2 days) and other drugs and that for autologous SCT included cyclophosphamide (50 mg/kg for 2 days) and other drugs. Total body irradiation (TBI) was employed only in the patients who received allogeneic SCT.<br> <b>Method:</b> Plasma BNP was measured using a radioimmunoassay for human BNP before and after SCT.<br> <b>Results:</b> In 13 of 15 patients, BNP levels were elevated after SCT. In patients who received a total body irradiation (TBI) of 13.2 Gy, BNP levels were higher than those without irradiation (p=0.01). The BNP level reached a peak within 6 months after SCT in most patients and fell thereafter. But 7 of the 15 patients (46.7%) had an abnormally high level of plasma BNP even after 6 months of SCT which suggests subclinical myocardial damage.<br> <b>Conclusion:</b> A rise in plasma BNP was frequently observed after SCT, and may be considered to represent cardiac damage caused by the preparative chemotherapy and/or total body irradiation. Since a rise was noted 6 months after SCT, long-term evaluation of cardiac function is important.<br>

DOI： 10.2169/internalmedicine.46.6188

その他リンク： http://search.jamas.or.jp/link/ui/2007315596

Expression of BAFF-R (BR3) in normal and neoplastic lymphoid tissues characterized with a newly developed monoclonal antibody 査読

N Nakamura, H Hase, D Sakurai, S Yoshida, M Abe, N Tsukada, J Takizawa, S Aoki, M Kojima, S Nakamura, T Kobata

VIRCHOWS ARCHIV 447 ( 1 ) 53 - 60 2005年7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：SPRINGER

BAFF-receptor (BAFF-R) is required for the successful maturation and survival of B-cells. We developed an anti-human BAFF-R monoclonal antibody (mAb), 8A7. The reactivity of 8A7 in normal and neoplastic tissue was examined by performing immunohistochemistry on paraffin-embedded sections. 8A7 reacted with lymphocytes in the mantle and marginal zones, but not with lymphocytes in the interfollicular area. Lymphocytes in the germinal centers were found to be negative or occasionally weakly positive for 8A7. BAFF-R expression was found only in B-cell lymphoma (44/80, positive cases/examined cases): B-lymphoblastic lymphoma 0/3, B-chronic lymphocytic leukemia/small lymphocytic lymphoma 4/4, mantle cell lymphoma 9/11, follicular lymphoma 10/14, diffuse large B-cell lymphoma (DLBCL) 11/25, marginal zone B-cell lymphoma 8/10, lymphoplasmacytic lymphoma 2/2, plasma cell myeloma 0/2, and Burkitt lymphoma 0/9, but not in T/NK cell lymphomas (0/19) or Hodgkin lymphoma (0/10). BAFF-R was expressed in most low-grade B-cell neoplasms and a small number of DLBCL, suggesting that BAFF-R may play an important role in the proliferation of neoplastic lymphoid cells. Thus, the mAb is very useful for further understanding of both healthy B-cell biology and its pathogenic neoplasms.

DOI： 10.1007/s00428-005-1275-6

IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy 査読

G Hatzivassiliou, Miller, I, J Takizawa, N Palanisamy, PH Rao, S Iida, S Tagawa, M Taniwaki, J Russo, A Neri, G Cattoretti, R Clynes, C Mendelsohn, RSK Chaganti, R Dalla-Favera

IMMUNITY 14 ( 3 ) 277 - 289 2001年3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：CELL PRESS

Abnormalities of chromosome 1q21 are common in B cell malignancies, but their target genes are largely unknown. By cloning the breakpoints of a (1;14) (q21;q32) chromosomal translocation in a myeloma cell line, we have identified two novel genes, IRTA1 and IRTA2, encoding cell surface receptors homologous to the Fc and inhibitory receptor families. Both genes are selectively expressed in mature B cells: IRTA1 in marginal zone B cells and IRTA2 in centrocytes, marginal zone B cells, and immunoblasts. As a result of the t(1;14), IRTA1 is fused to the immunoglobulin C alpha domain to produce a chimeric IRTA1/C alpha fusion protein. In tumor cell lines with 1q21 abnormalities, IRTA2 expression is deregulated. Thus, IRTA1 and IRTA2 are novel immunoreceptors implicated in B cell development and lymphomagenesis.

DOI： 10.1016/S1074-7613(01)00109-1

5q- syndrome presenting chronic myeloproliferative disorders-like manifestation: A case report 査読

Hidenobu Takahashi, Tatsuo Furukawa, Shigeo Hashimoto, Naoko Kanazawa, Naoaki Satoh, Noriatsu Suzuki, Jun Takizawa, Yumiko Uesugi, Masuhiro Takahashi, Yoshifusa Aizawa, Tadashi Koike

American Journal of Hematology 64 ( 2 ) 120 - 123 2000年

記述言語：英語掲載種別：研究論文（学術雑誌）

A 28-year-old Japanese woman with suspected essential thrombocythemia (ET) had marked thrombocytosis, mild leukocytosis with normal neutrophil alkaline phosphatase activity, and no anemia. She was monitored without being given any medication. Eleven years later, complete blood counts showed no remarkable changes but some non-lobulated mononuclear megakaryocytes were found in the bone marrow. Cytogenetic analysis revealed deletion of the long arm of chromosome 5 (5q-). Subsequently, hemoglobin and platelet counts decreased gradually, splenomegaly appeared and progressed, after which myelofibrosis developed. Acute leukemia developed 16 years after the first documentation of thrombocytosis. 5q- syndrome is known to be a myelodysplastic syndrome (MDS) with unique clinical features and cases with this syndrome presenting with thrombocytosis of more than 1,000 x 109/L but without anemia are rare. Furthermore, it is noteworthy that in this patient transition to acute leukemia occurred following development of myelofibrosis and marked splenomegaly, which are generally observed in blastic crises resulting from chronic myeloproliferative disorders (CMPD). The patient showed features indicative of CMPD rather than of MDS in spite of presenting with 5q- chromosomal abnormality. This case supports the concept of 'mixed myelodysplastic and myeloproliferative syndromes' and suggests the possibility of the appearance of CMPD-like manifestations in 5q- syndrome. (C) 2000 Wiley-Liss, Inc.

DOI： 10.1002/(SICI)1096-8652(200006)64:2<120::AID-AJH9>3.0.CO;2-M

The TCL1 oncogene is not overexpressed in patients with adult T cell leukemia 査読

J Takizawa, M Seto

LEUKEMIA 13 ( 2 ) 314 - 314 1999年2月

Expression of the TCL1 gene at 14q32 in B-cell malignancies but not in adult T-cell leukemia 査読

J Takizawa, R Suzuki, H Kuroda, A Utsunomiya, Y Kagami, T Joh, Y Aizawa, R Ueda, M Seto

JAPANESE JOURNAL OF CANCER RESEARCH 89 ( 7 ) 712 - 718 1998年7月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI IRELAND LTD

The TCL1 gene was recently cloned as a candidate target within the 14q32.1 breakpoint cluster region observed in T-cell malignancies. We examined the TCL1 gene expression in 21 patients with adult T-cell leukemia (ATL) and 5 cell Lines, because ATL is reported to have frequent chromosome 14 band (q32 aberrations, However, 20 of the ATL patients and all 5 cell lines lacked any TCL1 expression on northern blot analysis, and TCL1 transcripts were only very faintly detected in the remaining one patient, Expansion of our analysis to include other types of hematopoietic malignancies revealed strong expression of the TCL1 gene in almost all tumor cells of B-cell lineage except myelomas. However no TCL1 signals were encountered in cells of T-cell or myeloid lineages. In normal human tissues TCL1 was found to be expressed in the spleen. lymph nodes and B-lymphocytes of peripheral blood. These results indicate that TCL1 is not a major target gene for ATL, but that it may play a role in B-cell differentiation and proliferation.

DOI： 10.1111/j.1349-7006.1998.tb03275.x

Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation 査読

Tatsuroh Joh, Yoshitoyo Kagami, Kazuhito Yamamoto, Tatsuya Segawa, Jun Takizawa, Toshitada Takahashi, Ryuzo Ueda, Masao Seto

Oncogene 13 ( 9 ) 1945 - 1953 1996年

記述言語：英語掲載種別：研究論文（学術雑誌）

11q23 chromosome aberrations are frequently observed in infantile as well as therapy-related leukemias. The target gene at 11q23, MLL, is disrupted by the translocation and becomes fused to various translocation partner genes such as AF4/FEL, LTG9/AF9 and LTG19/ENL. The resulting chimeric mRNAs are fused in frame and have been predicted to encode leukemia-specific chimeric proteins. In the present study, we raised antibodies against MLL, LTG9 and LTG19 and demonstrated that MLL and chimeric MLL-LTG9 and MLL-LTG19 products are synthesized in vivo and are localized in the nuclei, using immunofluorescence and cell fractionation studies. The truncated N-terminal portion of the MLL product common to the various types of 11q23 translocation was also localized in the nuclei in a similar fashion. Murine 32Dc13 cells stably expressing the truncated N-terminal MLL protein exhibited an inhibition of differentiation and a growth advantage following stimulation by granulocyte-colony stimulating factor, although the IL-3 dependency was not significantly changed in comparison to the parental cells. These results suggest that the N-terminal portion common to various MLL-chimeric products plays an important role in leukemogenesis.

Fanconi貧血と思われる再生不良性貧血に続発した急性骨髄性白血病に親子間同種骨髄移植を施行した1症例査読

瀧澤淳, 岸賢治, 森山美昭, 橋本誠雄, 後藤隆夫, 樋口渉, 和田研, 成田美和子, 青木定夫, 高橋益広, 小池正, 柴田昭

臨床血液 36 ( 6 ) 615 - 620 1995年6月

担当区分：筆頭著者記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本血液学会

症例は19歳，男性。生後1カ月より貧血を指摘され，低身長，右母指形成不全，皮膚色素沈着，精神発達遅延など多発奇形を合併しており，Fanconi貧血(FA)が疑われ経過観察されてきた。1993年1月より，汎血球減少が著明となり，頻回の輸血が必要となったため，8月31日当科入院となった。入院時骨髄穿刺では，骨髄は有核細胞数1.1×10<sup>4</sup>/μ<i>l</i>と低形成であったが，芽球42.0%, 前骨髄球9.6%を認め，AML (M2)へ移行したものと判断した。少量Ara-C療法で寛解は得られず，HLA完全一致，MLC陰性の父親をdonorとして，10月15日同種骨髄移植を施行した。移植前処置はcyclophosphamideを用いず，Ara-Cとetoposideの大量投与とTBI (12Gy)を併用したが，重篤なregimen related toxicityは認めず，骨髄生着が得られた。急性GVHD予防はciclosporin Aとmethotrexateを用い，GVHDは認められなかった。白血病に移行したFAに対するBMT成功例は少なく，文献的考察を含め報告する。

DOI： 10.11406/rinketsu.36.615

T細胞前リンパ球性白血病(T-PLL)に対するアレムツズマブ日本リンパ網内系学会診療保険委員会による国内使用実態調査(ATP study)

山口素子, 宮崎香奈, 名藤佑真, 市川聡, 福原規子, 鈴木隆晴, 瀧澤淳, 島晃大, 石塚賢治, 宮澤悠里, 横濱章彦, 伊豆津宏二, 鈴木律朗, 永井宏和, 中村直哉

日本リンパ網内系学会会誌 64 91 - 91 2024年5月

同種造血幹細胞移植後の慢性GVHDとしての類上皮肉芽腫および多発筋炎

諏訪部達也, 布施香子, 水戸部正樹, 武田ルイ, 米沢穂高, 片桐隆幸, 河本啓介, 牛木隆志, 柴崎康彦, 瀧澤淳, 成田美和子, 曽根博仁, 大島孝一, 増子正義

臨床血液 62 ( 6 ) 675 - 675 2021年6月

陰茎・陰嚢病変を合併した精巣原発DLBCL

水戸部正樹, 武田ルイ, 米沢穂高, 田村秀, 諏訪部達也, 片桐隆幸, 河本啓介, 布施香子, 柴崎康彦, 増子正義, 井上佳菜子, 三好寛明, 大島孝一, 曽根博仁, 瀧澤淳

臨床血液 62 ( 6 ) 668 - 668 2021年6月

乾燥人フィブリノゲン製剤の継続輸注で着床・妊娠継続・出産をし得た先天性低フィブリノゲン血症

関義信, 牛木隆志, 増子正義, 瀧澤淳, 曽根博仁, 奥村伸生

日本血栓止血学会誌 32 ( 2 ) 214 - 214 2021年5月

GB療法施行中にHigh-grade B-cell lymphoma with MYC and BCL2 rearrangementsで再燃したFollicular lymphoma(Grade 3A)の2症例

水戸部正樹, 本宮奈津子, 武田ルイ, 米沢穂高, 鈴木隆晴, 諏訪部達也, 片桐隆幸, 河本啓介, 布施香子, 柴崎康彦, 増子正義, 井上佳菜子, 三好寛明, 大島孝一, 曽根博仁, 瀧澤淳

日本リンパ網内系学会会誌 61 114 - 114 2021年5月

腎障害を有する高悪性度B細胞リンパ腫症例にDA-EPOCH-Rを施行した1例

水戸部正樹, 河本啓介, 鈴木隆晴, 米沢穂高, 田村秀, 諏訪部達也, 根本洋樹, 布施香子, 柴崎康彦, 増子正義, 三好寛明, 大島孝一, 曽根博仁, 瀧澤淳

臨床血液 62 ( 5 ) 532 - 532 2021年5月

ルキソルチニブ・ヒドロキシウレア併用療法が奏効した慢性好中球性白血病(CNL)の1例

武田ルイ, 布施香子, 片桐隆幸, 河本啓介, 柴崎康彦, 瀧澤淳, 成田美和子, 野本信彦, 曽根博仁, 増子正義

臨床血液 62 ( 5 ) 529 - 530 2021年5月

乾燥人フィブリノゲン製剤の継続輸注で着床・妊娠継続・出産をし得た先天性低フィブリノゲン血症

関義信, 牛木隆志, 増子正義, 瀧澤淳, 曽根博仁, 奥村伸生

日本血栓止血学会誌 32 ( 2 ) 214 - 214 2021年5月

ルキソルチニブ・ヒドロキシウレア併用療法が奏効した慢性好中球性白血病(CNL)の1例

武田ルイ, 布施香子, 片桐隆幸, 河本啓介, 柴崎康彦, 瀧澤淳, 成田美和子, 野本信彦, 曽根博仁, 増子正義

臨床血液 62 ( 5 ) 529 - 530 2021年5月

GB療法施行中にHigh-grade B-cell lymphoma with MYC and BCL2 rearrangementsで再燃したFollicular lymphoma(Grade 3A)の2症例

水戸部正樹, 本宮奈津子, 武田ルイ, 米沢穂高, 鈴木隆晴, 諏訪部達也, 片桐隆幸, 河本啓介, 布施香子, 柴崎康彦, 増子正義, 井上佳菜子, 三好寛明, 大島孝一, 曽根博仁, 瀧澤淳

日本リンパ網内系学会会誌 61 114 - 114 2021年5月

腎障害を有する高悪性度B細胞リンパ腫症例にDA-EPOCH-Rを施行した1例

水戸部正樹, 河本啓介, 鈴木隆晴, 米沢穂高, 田村秀, 諏訪部達也, 根本洋樹, 布施香子, 柴崎康彦, 増子正義, 三好寛明, 大島孝一, 曽根博仁, 瀧澤淳

臨床血液 62 ( 5 ) 532 - 532 2021年5月

Langerhans細胞組織球症(LCH)患者に生じた皮膚肥満細胞症の1例

武居慎吾, 濱菜摘, 岩井由樹, 結城明彦, 阿部理一郎, 長崎啓祐, 米沢穂高, 瀧澤淳, 梅津哉, 柿田明美

日本皮膚科学会雑誌 130 ( 7 ) 1662 - 1662 2020年6月

Langerhans細胞組織球症(LCH)患者に生じた皮膚肥満細胞症の1例

武居慎吾, 濱菜摘, 岩井由樹, 結城明彦, 阿部理一郎, 長崎啓祐, 米沢穂高, 瀧澤淳, 梅津哉, 柿田明美

日本皮膚科学会雑誌 130 ( 3 ) 419 - 419 2020年3月

骨髄異形成症候群と低悪性度B細胞リンパ腫を合併し、多彩な合併症を呈した1例

海發茜, 小堺貴司, 田村秀, 片桐隆幸, 河本啓介, 難波亜矢子, 布施香子, 牛木隆志, 柴崎康彦, 森山雅人, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

臨床血液 60 ( 10 ) 1503 - 1503 2019年10月

Hodgkin lymphomaとAnaplastic large cell lymphomaの鑑別が困難であった巨大縦隔腫瘤を呈した1例

河本啓介, 鈴木隆晴, 海發茜, 田村秀, 片桐隆之, 難波亜矢子, 布施香子, 柴崎康彦, 増子正義, 曽根博仁, 三好寛明, 大島孝一, 瀧澤淳

日本リンパ網内系学会会誌 59 133 - 133 2019年5月

日本では未分類である脾臓B細胞リンパ腫/白血病におけるBRAF遺伝子変異の分析(Analysis of BRAF mutation in splenic B-cell lymphoma/leukemia, unclassifiable in Japan)

鈴木隆晴, 三好寛明, 河本啓介, 荒川文子, 古田拓也, 下埜城嗣, 山田恭平, 柳田恵理子, 瀬戸加大, 曽根博仁, 瀧澤淳, 大島孝一

日本リンパ網内系学会会誌 59 145 - 145 2019年5月

芽球性形質細胞様樹状細胞腫瘍におけるMYC異常免疫芽球様細胞形態、薬剤感受性との関連(Recurrent MYC alteration in BPDCN: association with immunoblastoid morphology and drug response)

坂本佳奈, 片山量平, 朝賀礼美, 坂田征士, 馬場郷子, 仲宗根秀樹, 小池清恵, 津山直子, 土橋映仁, 佐々木純, 一迫玲, 高桑恵美, 山崎理絵, 瀧澤淳, 前田隆浩, 成田美和子, 伊豆津宏二, 神田善伸, 大島孝一, 竹内賢吾

臨床血液 59 ( 9 ) 1503 - 1503 2018年9月

GDP療法がtriple-hit lymphomaの救援療法として有効であった1例

水戸部正樹, 河本啓介, 鈴木隆晴, 田村秀, 小堺貴司, 難波亜矢子, 諏訪部達也, 笠見卓哉, 田中智之, 布施香子, 柴崎康彦, 増子正義, 曽根博仁, 大島孝一, 瀧澤淳

臨床血液 59 ( 5 ) 620 - 621 2018年5月

抗原特異的細胞傷害性T細胞(CTL)の増幅と機能の検討

小川彩空, 増子正義, 後藤若奈, 内山孝由, 橋本誠雄, 柴崎康彦, 瀧澤淳, 成田美和子

日臨技北日本支部医学検査学会抄録集 6回 128 - 128 2017年10月

ボルテゾミブが奏功した意義不明の単クローン性ガンマグロブリン血症(MGUS)に伴う重鎖沈着症(HCDD)の一例

須藤真則, 若松拓也, 石川友美, 羽深将人, 細島康宏, 山本卓, 伊藤由美, 今井直史, 金子佳賢, 瀧澤淳, 成田一衛

日本腎臓学会誌 59 ( 6 ) 869 - 869 2017年9月

Peripheral T-cell lymphoma, not otherwise specified: a retrospective single-center analysis. 査読

Suzuki T, Kawamoto K, Tamura S, Uemura S, Kaihatsu A, Nemoto H, Kobayashi H, Ushiki T, Fuse K, Shibazaki Y, Moriyama M, Masuko M, Narita M, Sone H, Aoki S, Nakamura N, Oshima K, Takizawa J

[Rinsho ketsueki] The Japanese journal of clinical hematology 58 ( 8 ) 905 - 911 2017年

[Myelodysplastic syndrome with refractory hemorrhage due to reduced platelet aggregation activity]. 査読

Tanaka T, Kozakai T, Kitajima T, Fuse K, Kobayashi H, Ushiki T, Shibazaki Y, Moriyama M, Takizawa J, Sone H, Fuse I, Masuko M

[Rinsho ketsueki] The Japanese journal of clinical hematology 58 ( 12 ) 2402 - 2405 2017年

記述言語：日本語出版者・発行元：一般社団法人日本血液学会

<p>症例は75歳の女性。血液検査で貧血と末梢血に芽球を認められたため，当院を紹介受診した。骨髄穿刺で骨髄異形成症候群（myelodysplastic syndrome with excess blasts 2, MDS-EB-2）と診断された。血球減少の進行や芽球の増加，および出血症状はなく経過していた。診断から10ヶ月後，左手母指球に外傷を負い，内出血が持続し，止血困難となったため緊急入院した。血小板数は正常範囲であったが，血小板機能検査でコラーゲン凝集能とアラキドン酸凝集能の低下を認められた。抗血小板薬の内服はなく，またこれまで出血傾向の既往もなかったことから，MDSによる2次性の血小板機能低下による出血と判断し，血小板輸血を行い止血した。MDSの患者では，潜在的に血小板凝集能が低下していることが多く，血小板数の割に出血傾向が強い場合には血小板凝集能を調べ，血小板輸血などの治療介入を検討する必要がある。</p>

DOI： 10.11406/rinketsu.58.2402

その他リンク： http://search.jamas.or.jp/link/ui/2018121562

扁桃・リンパ節に多発性myeloid sarcomaを生じたMDSの1例

片桐隆幸, 牛木隆志, 田中智之, 宮腰淑子, 難波亜矢子, 河本啓介, 柴崎康彦, 瀧澤淳, 成田美和子, 曽根博仁, 青木定夫, 増子正義

臨床血液 57 ( 11 ) 2415 - 2415 2016年11月

輸血依存患者における肝臓内鉄含有量を評価するための二重エネルギーCTの重要性(Significance of dual-energy CT to evaluate liver iron content in transfusion-dependent patients)

Kobayashi Hironori, Yoshimura Norihiko, Suwabe Tatsuya, Katagiri Takayuki, Miyakoshi Shukuko, Ushiki Takashi, Fuse Kyoko, Shibasaki Yasuhiko, Moriyama Masato, Takizawa Jun, Narita Miwako, Sone Hirohito, Masuko Masayoshi

臨床血液 57 ( 9 ) 1524 - 1524 2016年9月

Clinical Significance of MYC, BCL2 and BCL6 Rearrangement and Protein Expression in GCB and Non-GCB Type Diffuse Large B-Cell Lymphoma 招待査読

Kawamoto Keisuke, Takizawa Jun, Miyoshi Hiroaki, Yoshida Noriaki, Shibasaki Yasuhiko, Masuko Masayoshi, Sone Hirohito, Nakamura Naoya, Ohshima Koichi

BLOOD 126 ( 23 ) 2015年12月

レシピエントに対する移植前評価としてのHCT-CI/年齢スコアの臨床的意義(The clinical relevance of HCT-CI/age score as pre-transplant assessment for recipients)

Katagiri Takayuki, Shibasaki Yasuhiko, Suwabe Tatsuya, Miyakoshi Shukuko, Fuse Kyoko, Kobayashi Hironori, Ushiki Takashi, Moriyama Masato, Takizawa Jun, Narita Miwako, Sone Hirohito, Masuko Masayoshi

臨床血液 56 ( 9 ) 1665 - 1665 2015年9月

HSCT後のγ/δT細胞低値およびTreg細胞高値はいずれも再発の独立リスク因子である(Both low γ/δ T cells and high Treg cells after HSCT is an independent risk factor for relapse)

Shibasaki Yasuhiko, Miyakoshi Syukuko, Suwabe Tatsuya, Katagiri Takayuki, Fuse Kyoko, Kobayashi Hironori, Ushiki Takashi, Moriyama Masato, Takizawa Jun, Narita Miwako, Sone Hirohito, Furukawa Tatsuo, Masuko Masayoshi

臨床血液 56 ( 9 ) 1666 - 1666 2015年9月

鼠径部皮下腫瘤から診断されたびまん性大細胞型B細胞リンパ腫の1例

吉長由季菜, 藤川大基, 株本武範, 伊藤雅章, 片桐隆幸, 瀧澤淳

日本皮膚科学会雑誌 125 ( 4 ) 947 - 947 2015年4月

Log Reduction Levels of WT1 mRNA Expression in BM after Chemotherapies Are Predictive Markers of Good Prognosis in AML Patients Achieved CR after Induction Therapy 査読

Yasuhiko Shibasaki, Yoshinobu Seki, Tomoyuki Tanaka, Syukuko Miyakoshi, Kyoko Fuse, Takashi Kozakai, Hironori Kobayashi, Takashi Ushiki, Takashi Abe, Toshio Yano, Masato Moriyama, Takashi Kuroha, Noriatsu Isahai, Jun Takizawa, Miwako Narita, Satoru Koyama, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

BLOOD 124 ( 21 ) 2014年12月

Imaging of Body Iron Stores in Transfusion-Dependent Patients By Liver Dual-Energy CT 査読

Hironori Kobayashi, Norihiko Yoshimura, Takashi Ushiki, Yasuhiko Shibasaki, Masato Moriyama, Jun Takizawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko

BLOOD 124 ( 21 ) 2014年12月

血液悪性腫瘍患者における真菌感染症に対するvoriconazoleの有効性と安全性(Efficacy and safety of Voriconazole on fungal infections in patients with hematological malignancies)

Miyakoshi Shukuko, Takizawa Jun, Seki Yoshinobu, Maruyama Souichi, Karimata Kaori, Kobayashi Hironori, Ida Tori, Momoi Akihito, Yano Toshio, Kuroha Takashi, Ushiki Takashi, Nikkuni Koji, Nomoto Nobuhiko, Nagai Koichi, Aoki Sadao

臨床血液 53 ( 9 ) 1092 - 1092 2012年9月

Idiopathic Macrocytosis in Smokers

Masuhiro Takahashi, Akie Yamahira, Takayoshi Uchiyama, Minami Iwabuchi, Naoya Sato, Jun Takizawa, Hirohito Sone, Miwako Narita

人間ドック (Ningen Dock) 27 ( 4 ) 689 - 696 2012年

記述言語：日本語出版者・発行元：Japan Society of Ningen Dock

<b>Objective:</b> Smoking has been reported to be one of the risk factors of myelodysplastic syndrome (MDS). In order to clarify the process of progression to MDS in a certain group of smokers, it is important to identify the initial hematological abnormalities associated with the early stage of MDS in smokers. <br><b>Methods:</b> Relationships of hematological parameters such as WBC count, RBC count, Hb, Ht, MCH and MCV with level of smoking were investigated by univariate and multivariate analyses in 234 male workers at a single workplace after obtaining informed consent.<br><b>Results:</b> Univariate analysis demonstrated that correlations of smoking-related factors (number of cigarettes per day, duration of smoking [years] and smoking index [defined as number of cigarettes per day x duration of smoking]) with WBC count, Ht, MCH and MCV were significantly positive. Multivariate analysis using age, smoking-related factors, alcohol intake and BMI as explanatory valuables showed that age, alcohol intake and BMI were not confounding variables for smoking-related factors and revealed a remarkable significant positive correlation between each smoking-related factor and MCV.<br><b>Conclusion:</b> Smoking-associated macrocytosis, which was demonstrated in the present study, was not due to deficiency of vitamin B<sub>12</sub> or folic acid because of no pancytopenia observed but was considered to be a qualitative abnormality of erythrocytes. Taken together with the findings of previous studies concerning smoking-associated functional abnormalities of erythrocytes and leukocytes and the high incidence of MDS in smokers, our results indicate that idiopathic macrocytosis in smokers could be an initial sign of progression to MDS, in which macrocytosis and multi-lineage abnormalities are characteristic findings.

DOI： 10.11320/ningendock.27.689

その他リンク： https://jlc.jst.go.jp/DN/JALC/10013821561?from=CiNii

4. MALTリンパ腫による転移性気管腫瘍の1例(第54回日本呼吸器内視鏡学会北陸支部会)

三浦理, 森山寛史, 星野芳史, 小屋俊之, 中山秀章, 各務博, 高田俊範, 成田一衛, 吉永清宏, 小堺貴司, 瀧澤淳, 鈴木栄一, 味岡洋一

気管支学 34 ( 4 ) 407 - 407 2012年

咽頭・気管に再発した肺MALTリンパ腫の1例査読

田中淳一, 田島俊児, 梶原大季, 茂呂寛, 成田淳一, 田邊嘉也, 各務博, 中山秀章, 寺田正樹, 高田俊範, 成田一衛, 瀧澤淳, 長谷川隆志, 鈴木栄一, 中村直哉, 手塚貴文, 今井洋介

気管支学 32 ( 1 ) 84 - 84 2010年1月

長期間左内頸CVカテーテル留置により発生し、右心房直上まで及んだ巨大血栓に対して大静脈フィルターを用い、救命し得た1例

岡本竹司, 榛澤和彦, 佐藤浩一, 林純一, 瀧澤淳, 桃井明仁, 下田傑, 布施一郎

新潟医学会雑誌 122 ( 5 ) 288 - 288 2008年5月

ATIII低下を伴うDICを合併したAPLの1例

柴崎康彦, 橋本誠雄, 鳥羽健, 柳川貴央, 瀧澤淳, 相澤義房

新潟医学会雑誌 116 ( 11 ) 567 - 567 2002年11月

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