Faculty Profiles - MAEDA Yoshinobu

An Open-labeled, Multicenter Phase II Study of Tamibarotene in Patients with Steroid-refractory Chronic Graft-versus-Host Disease

Yoshinobu Maeda, Hisakazu Nishimori, Yoshihiro Inamoto, Hirohisa Nakamae, Masashi Sawa, Yasuo Mori, Kazuteru Ohashi, Shin-Ichiro Fujiwara, Mitsune Tanimoto

ACTA MEDICA OKAYAMA 70 ( 5 ) 409 - 412 2016.10

Language：English Publisher：OKAYAMA UNIV MED SCHOOL

Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HSCT). Retinoic acid (tamibarotene) exerts multiple effects on cell differentiation and is clinically used for the treatment of acute promyelocytic leukemia. Tamibarotene down-regulates both Th1 and Th17 differentiation in donor T cells after allogeneic HSCT, resulting in attenuation of experimental chronic GVHD. Based on preclinical data, we have launched a phase II study of tamibarotene in patients with steroid-refractory chronic GVHD. This study will clarify whether tamibarotene can exert beneficial effects in patients with steroid-refractory chronic GVHD.

DOI： 10.18926/AMO/54603

A phase II study of topotecan and cisplatin with sequential thoracic radiotherapy in elderly patients with small-cell lung cancer: Okayama Lung Cancer Study Group 0102

Toshio Kubo, Keiichi Fujiwara, Katsuyuki Hotta, Toshiaki Okada, Shoichi Kuyama, Shingo Harita, Takashi Ninomiya, Haruhito Kamei, Shinobu Hosokawa, Akihiro Bessho, Tadashi Maeda, Toshiyuki Kozuki, Nobukazu Fujimoto, Kiichiro Ninomiya, Mitsuhiro Takemoto, Susumu Kanazawa, Nagio Takigawa, Masahiro Tabata, Mitsune Tanimoto, Hiroshi Ueoka, Katsuyuki Kiura

CANCER CHEMOTHERAPY AND PHARMACOLOGY 78 ( 4 ) 769 - 774 2016.10

Language：English Publisher：SPRINGER

Purpose The treatment outcome in elderly patients with limited-disease small-cell lung cancer (LD-SCLC) remains poor. We carried out a phase II trial of split topotecan and cisplatin (TP) therapy and sequential thoracic radiotherapy for elderly LD-SCLC patients as a follow-up to our previous phase I trial.
Methods In total, 30 patients aged 76 years or older, with untreated LD-SCLC were enrolled. Four courses of topotecan (1.0 mg/m(2), days 1-3) and cisplatin (20 mg/m(2), days 1-3) were administered, followed by thoracic radiotherapy (1.8 Gy/day, total of 45 Gy). The primary end point was the overall response rate (ORR).
Results The trial was terminated early with 22 patients because of slow accrual. Their median age was 79 years. The median number of courses of chemotherapy administered was three, and the actual completion rate of the entire treatment course was 41 %. The ORR was 68 % with a 95 % confidence interval of 47-89 % (15/22 cases). The median progression-free survival and overall survival were 9.1 and 22.2 months, respectively. The main toxicity was myelosuppression, with grades 3-4 neutropenia (96 %), thrombocytopenia (50 %), and febrile neutropenia (32 %).
Conclusions This regimen produced a favorable survival outcome, despite moderate-to-severe toxicity profiles. Further efforts are necessary to define an optimal regimen for elderly patients with limited SCLC.

DOI： 10.1007/s00280-016-3135-2

An Open-labeled, Multicenter Phase II Study of Tamibarotene in Patients with Steroid-refractory Chronic Graft-versus-Host Disease

Yoshinobu Maeda, Hisakazu Nishimori, Yoshihiro Inamoto, Hirohisa Nakamae, Masashi Sawa, Yasuo Mori, Kazuteru Ohashi, Shin-Ichiro Fujiwara, Mitsune Tanimoto

ACTA MEDICA OKAYAMA 70 ( 5 ) 409 - 412 2016.10

Language：English Publisher：OKAYAMA UNIV MED SCHOOL

DOI： 10.18926/AMO/54603

Clinicopathological features of 49 primary gastrointestinal diffuse large B-cell lymphoma cases; comparison with location, cell-of-origin, and frequency of MYD88 L265P International journal

Keina Nagakita, Katsuyoshi Takata, Kohei Taniguchi, Tomoko Miyata-Takata, Yasuharu Sato, Akira Tari, Nobuhiko Ohnishi, Mai Noujima-Harada, Shizuma Omote, Naoya Nakamura, Masaya Iwamuro, Yoshinobu Maeda, Hiroyuki Okada, Mitsune Tanimoto, Tadashi Yoshino

PATHOLOGY INTERNATIONAL 66 ( 8 ) 444 - 452 2016.8

Language：English Publisher：WILEY-BLACKWELL

The gastrointestinal (GI) tract is the most common primary site of extranodal diffuse large B-cell lymphoma (DLBCL), with approximately one-third of extranodal DLBCL occurring in the GI tract. We investigated the clinicopathological features and immunohistochemically-assessed cell-of-origin of 49 GI DLBCL cases (stomach, 24; small intestine, 10; colon, 15) and also examined the presence of MYD88 L265P as recently this mutation has been frequently identified in ABC-like DLBCL, particularly in extranodal sites. Small intestinal DLBCL was characterized by the preponderance of women (P = 0.041) and elevated LDH (P = 0.002) and soluble interleukin-2 receptor (P = 0.033). Small intestinal DLBCL more frequently showed anemia (P = 0.031) and elevated CRP (P = 0.029) than gastric DLBCL. ABC-like phenotype was seen in 71.4 % cases (stomach, 79 %; small intestine, 70 %; colon, 60 %). MYD88 L265P was detected in 6.1 % cases; all were primary gastric DLBCL with ABC-like phenotype but had no distinct clinicopathological features. In conclusion, GI DLBCL had different clinicopathological features according to the primary site especially in the small intestine. Also, MYD88 L265P had little involvement in GI DLBCL compared with other extranodal DLBCLs, suggesting that its pathogenesis might be different from that of organs with a high frequency of MYD88 L265P.

DOI： 10.1111/pin.12439

Clinicopathological features of 49 primary gastrointestinal diffuse large B-cell lymphoma cases; comparison with location, cell-of-origin, and frequency of MYD88 L265P

PATHOLOGY INTERNATIONAL 66 ( 8 ) 444 - 452 2016.8

Language：English Publisher：WILEY-BLACKWELL

DOI： 10.1111/pin.12439

Effects of new over-the-counter periodontal ointment-containing applicator with single-tuft brush on cytokine levels in gingival crevicular fluid during supportive periodontal therapy phase: A randomized double-blind clinical trial

K. Takeuchi-Hatanaka, T. Yasuda, K. Naruishi, K. Naruishi, K. Katsuragi-Fuke, K. Katsuragi-Fuke, J. Inubushi, H. Ootsuki, H. Ootsuki, H. Maeda, H. Maeda, S. Takashiba

Journal of Periodontal Research 51 ( 3 ) 321 - 331 2016.6

© 2016 John Wiley & Sons A/S. Background and Objective: The biochemical effects of an over-the-counter (OTC) medication were studied, which consists of a single-tuft brush containing cetylpyridinium chloride as a bactericidal agent, dipotassium glycyrrhizate as an anti-inflammatory drug and allantoin as a promoter of cell proliferation and wound healing, for delivery to hardly brushed sites. Material and Methods: This randomized controlled double-blind study was performed in 61 subjects with chronic periodontitis in supportive periodontal therapy phase (test group: n = 27; placebo group: n = 28; dropout: n = 6). The OTC medication was self-applied twice a day for 12 wk to two molars with probing pocket depths of 4-6 mm. Biochemical indicators were evaluated at baseline and 12 wk using the suspension array system for eight cytokines and chemokines (interleukin [IL]-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and tumor necrosis factor [TNF]-α) in gingival crevicular fluid. Results: The levels of IL-1β, IL-6, IL-8 and TNF-α remained significantly lower in the test group compared to the placebo group. In the placebo group, when the probing pocket depth at baseline was 4 mm, IL-1β increased, particularly in the second molar tooth, and the greatest increase was seen when PPD at baseline was 5-6 mm. In the test group, IL-1β decreased markedly in cases with furcation involvement and low bleeding on probing at baseline. In both groups, IL-1β, IL-6 and TNF-α were closely correlated with each other. Conclusion: This OTC medication is biochemically effective for steady chronic periodontitis in the supportive periodontal therapy phase.

DOI： 10.1111/jre.12311

Scopus

Efficacy of upfront high-dose chemotherapy plus rituximab followed by autologous peripheral blood stem cell transplantation for untreated high-intermediate-, and high-risk diffuse large B-cell lymphoma: a multicenter prospective phase II study (JSCT-NHL04)

Tohru Murayama, Takahiro Fukuda, Hirokazu Okumura, Kazutaka Sunami, Aiko Sawazaki, Yoshinobu Maeda, Hisashi Tsurumi, Naokuni Uike, Tomonori Hidaka, Yoshifusa Takatsuka, Tetsuya Eto, Hiroyuki Tsuda, Tomoaki Fujisaki, Toshihiro Miyamoto, Naoko Tsuneyoshi, Satoshi Iyama, Koji Nagafuji, Mine Harada

INTERNATIONAL JOURNAL OF HEMATOLOGY 103 ( 6 ) 676 - 685 2016.6

Language：English Publisher：SPRINGER JAPAN KK

To evaluate the efficacy and feasibility of upfront high-dose chemotherapy (HDCT) and rituximab (R) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) in patients with newly diagnosed high-intermediate(HI)-, and high(H)-risk diffuse large B-cell lymphoma (DLBCL), we conducted a multicenter prospective phase II trial. In 15-60-year-old patients with H- or HI-risk DLBCL, after three courses of (R-)CHOP14, high-dose etoposide was given prior to peripheral blood stem cell harvesting. After an additional three courses of (R-)CHOP14, auto-PBSCT was performed following HDCT. The primary endpoint of the study is progression-free survival (PFS) at 2 years after registration in eligible patients. The expected PFS and the threshold PFS were estimated to be 70 and 50 %, respectively. Among 40 eligible patients registered, 30 patients completed treatment. With a median observation period in surviving eligible patients of 63 months, the 2- and 4-year PFS after registration were 79.9 and 72.0 %, respectively. The 2- and 4-year overall survival (OS) were 92.5 and 84.6 %, respectively. In 30 patients who completed treatment, the 4-year PFS and OS after auto-PBSCT were 79.2 and 85.9 %, respectively. In conclusion, the results of our study suggest that upfront HDCT and auto-PBSCT combined with rituximab is highly effective as an initial treatment for HI-, and H-risk DLBCL.

DOI： 10.1007/s12185-016-1976-4

同種骨髄移植後にBKウイルス性出血性膀胱炎に罹患し、両側腎瘻・膀胱瘻造設術を要した骨髄異形成症候群の1症例

鴨井千尋, 三道康永, 藤井伸治, 吉田将平, 西森久和, 松岡賢市, 近藤英生, 前田嘉信, 谷本光音, 児島宏典, 森聰博, 藤尾圭, 堀川雄平, 松本裕子, 和田耕一郎, 那須保友

臨床血液 57 ( 5 ) 669 - 669 2016.5

Phase 1/2 study of forodesine in patients with relapsed peripheral t-cell lymphoma (PTCL).

Kunihiro Tsukasaki, Kensei Tobinai, Toshiki Uchida, Yoshinobu Maeda, Hirohiko Shibayama, Hirokazu Nagai, Mitsutoshi Kurosawa, Yasunobu Abe, Kiyohiko Hatake, Kiyoshi Ando, Isao Yoshida, Michihiro Hidaka, Tohru Murayama, Yoko Okitsu, Norifumi Tsukamoto, Masafumi Taniwaki, Junji Suzumiya, Kazuo Tamura, Takahiro Yamauchi, Ryuzo Ueda

JOURNAL OF CLINICAL ONCOLOGY 34 ( 15 ) 2016.5

リンパ節、肺・心嚢への進展を伴った皮膚原発ALK陰性ALCLの1例

為房宏輔, 猪股知子, 松岡賢市, 吉田将平, 西森久和, 近藤英生, 藤井伸治, 前田嘉信, 谷本光音

臨床血液 57 ( 5 ) 663 - 663 2016.5

Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

Hideaki Fujiwara, Yoshinobu Maeda, Yasuhisa Sando, Makoto Nakamura, Katsuma Tani, Tatsunori Ishikawa, Hisakazu Nishimori, Ken-Ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Mitsune Tanimoto

TRANSFUSION 56 ( 4 ) 886 - 892 2016.4

Language：English Publisher：WILEY

BACKGROUNDTransplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) remains a severe complication associated with underlying endothelial damage. TMA has a high mortality rate with no definite treatments and effective treatments are needed.
STUDY DESIGN AND METHODSThe study objective was to retrospectively analyze the outcome of patients receiving recombinant human soluble thrombomodulin (rTM), which has cytoprotective effects against calcineurin inhibitor-induced endothelial cell damage, or other therapeutics for TA-TMA from 254 consecutive HSCT recipients between 2009 to 2014 at a single institution. We hypothesized that patients receiving rTM as a first-line treatment would receive a benefit.
RESULTSSixteen patients were diagnosed as TA-TMA. Of these 16 patients, nine were treated with rTM (rTM group), and seven received treatment other than rTM (control group) as a first-line therapy. Seven of the nine patients in the rTM group recovered from TA-TMA without complications, but none in the control group recovered. The rTM group showed a significantly better overall survival after TA-TMA onset than did the control group (median, 123.0 days vs. 45.5 days, respectively; p=0.045). The cumulative incidence of acute graft-versus-host disease was the same in both groups (56% vs. 57%, respectively; p=0.52) on Day 100 after TA-TMA onset.
CONCLUSIONThis is the first report evaluating rTM administration for TA-TMA compared with previous treatments. Our data suggests that rTM might offer a better clinical outcome in patients with TA-TMA.

DOI： 10.1111/trf.13437

Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin International journal

Hideaki Fujiwara, Yoshinobu Maeda, Yasuhisa Sando, Makoto Nakamura, Katsuma Tani, Tatsunori Ishikawa, Hisakazu Nishimori, Ken-Ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Mitsune Tanimoto

TRANSFUSION 56 ( 4 ) 886 - 892 2016.4

Language：English Publisher：WILEY

DOI： 10.1111/trf.13437

Frequent MYD88 L265P and CD79B Mutations in Primary Breast Diffuse Large B-Cell Lymphoma International journal

Kohei Taniguchi, Katsuyoshi Takata, Shih-Sung Chuang, Tomoko Miyata-Takata, Yasuharu Sato, Akira Satou, Yuko Hashimoto, Maiko Tamura, Keina Nagakita, Nobuhiko Ohnishi, Mai Noujima-Harada, Tetsuya Tabata, Yara Yukie Kikuti, Yoshinobu Maeda, Naoya Nakamura, Mitsune Tanimoto, Tadashi Yoshino

AMERICAN JOURNAL OF SURGICAL PATHOLOGY 40 ( 3 ) 324 - 334 2016.3

Language：English Publisher：LIPPINCOTT WILLIAMS & WILKINS

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare disease comprising < 3% of extranodal lymphomas. It frequently reveals an activated B-cell (ABC)-like phenotype. ABC-like DLBCL was reported to have gain-of-function mutations in MYD88, CD79B, CARD11, and TNFAIP3, resulting in constitutive activation of the NF kappa B pathway. Because of the rare occurrence of PB-DLBCL, the frequency of MYD88 and CD79B mutations is still unknown. We used Sanger sequencing to study these mutations from 46 breast DLBCL cases and also investigated the associated clinicopathologic factors. MYD88 L265P was confirmed by allele-specific polymerase chain reaction and compared with the Sanger sequencing results. MYD88 L265P and CD79B mutations were detected in 27/46 (58.7%) and 11/33 (33.3%) cases, respectively. Twenty-eight of 46 cases met the criteria for PB-DLBCL, and the latter 18 cases were further classified as clinical breast DLBCL (CLB-DLBCL). The frequency of MYD88 L265P and CD79B mutations was 16/28 (57.1%) and 9/23 (39.1%), respectively, in PB-DLBCL and 11/18 (61.1%) and 2/10 (20%), respectively, in CLB-DLBCL. When the cutoff value was set at Delta Ct <= 1, the result of allele-specific polymerase chain reaction for MYD88 corresponded to those of the Sanger sequence at 92.6% sensitivity and 100% specificity. According to Choi's algorithm, 16/27 (59.3%) demonstrated an ABC-like phenotype in PB-DLBCL, and 15/18 (83.3%) demonstrated an ABC-like phenotype in CLB-DLBCL. In conclusion, MYD88 L265P and CD79B mutations were frequently detected in PB-DLBCL, and they may be key molecules associated with PB-DLBCL lymphomagenesis. Further analysis will be required to clarify the mechanism of its pathogenesis.

DOI： 10.1097/PAS.0000000000000592

A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis International journal

Seok Jin Kim, Dok Hyun Yoon, Arnaud Jaccard, Wee Joo Chng, Soon Thye Lim, Huangming Hong, Yong Park, Kian Meng Chang, Yoshinobu Maeda, Fumihiro Ishida, Dong-Yeop Shin, Jin Seok Kim, Seong Hyun Jeong, Deok-Hwan Yang, Jae-Cheol Jo, Gyeong-Won Lee, Chul Won Choi, Won-Sik Lee, Tsai-Yun Chen, Kiyeun Kim, Sin-Ho Jung, Tohru Murayama, Yasuhiro Oki, Ranjana Advani, Francesco d'Amore, Norbert Schmitz, Cheolwon Suh, Ritsuro Suzuki, Yok Lam Kwong, Tong-Yu Lin, Won Seog Kim

LANCET ONCOLOGY 17 ( 3 ) 389 - 400 2016.3

Language：English Publisher：ELSEVIER SCIENCE INC

Background The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted.
Methods We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
Findings We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
Interpretation PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.

DOI： 10.1016/S1470-2045(15)00533-1