研究者詳細 - 増子　正義

Effect of Granulocyte Colony-Stimulating Factor-Combined Conditioning in Cord Blood Transplantation for Myelodysplastic Syndrome and Secondary Acute Myeloid Leukemia: A Retrospective Study in Japan. 査読

Konuma T, Takahashi S, Uchida N, Kuwatsuka Y, Yamasaki S, Aoki J, Onishi Y, Aotsuka N, Ohashi K, Mori T, Masuko M, Nakamae H, Miyamura K, Kato K, Atsuta Y, Kato S, Asano S, Takami A, Miyazaki Y, Adult Myelodysplastic Syndrome, Adult Acute Myeloid, Leukemia Working, Group of, the Japan, Society for, Hematopoietic Cell Transplantation

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 21 ( 9 ) 1632 - 1640 2015年9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

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

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

Annals of the American Thoracic Society 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

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

LEUKEMIA RESEARCH 39 ( 6 ) 667 - 671 2015年6月

担当区分：最終著者,　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：PERGAMON-ELSEVIER SCIENCE LTD

We focused on the level of reduction of Wilms' tumor gene 1 (WT1) mRNA in bone marrow as minimal residual disease during chemotherapies in adult acute myeloid leukemia (AML) patients. Forty-eight patients were enrolled in this study. Log levels of reduction of WT1 mRNA transcript after induction therapy compared with those at diagnosis were associated with disease-free survival (DFS) (P = 0.0066) and overall survival (OS) (P = 0.0074) in patients who achieved complete remission. Also log levels of reduction of WT1 mRNA transcript after final consolidation therapy compared with those at diagnosis were associated with DFS (P = 0.015) and OS (P = 0.012). By multivariate analysis, log levels of reduction of WT1 mRNA transcript after induction therapy and after final consolidation therapy compared with those at diagnosis were extracted as risk factors for outcome. Our results suggest that early and deep reduction of tumor burden may be important for the outcome of AML patients. In addition, it may be useful for the decision to proceed with allogeneic SCT as post-remission therapy. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.leukres.2015.03.021

A Safety and Efficacy Study of Medium-Dose Etoposide, Cyclophosphamide and Total Body Irradiation Conditioning Before Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia. 査読国際誌

Shigematsu A, Ozawa Y, Onizuka M, Fujisawa S, Suzuki R, Atsuta Y, Hatanaka K, Masuko M, Ito T, Kobayashi N, Kato J, Miyamura K, Fukuda T, Morishima Y, Imamura M

Transplantation direct 1 ( 2 ) e8 2015年3月

Late Onset Post-Transfusion Hepatitis E Developing during Chemotherapy for Acute Promyelocytic Leukemia 査読

Kyoko Fuse, Yuichi Matsuyama, Masato Moriyama, Shukuko Miyakoshi, Yasuhiko Shibasaki, Jun Takizawa, Tatsuo Furukawa, Ichiro Fuse, Hiro Matsumura, Shigeharu Uchida, Yoshifumi Takahashi, Kenya Kamimura, Hiroyuki Abe, Takeshi Suda, Yutaka Aoyagi, Hirohito Sone, Masayoshi Masuko

INTERNAL MEDICINE 54 ( 6 ) 657 - 661 2015年

担当区分：最終著者,　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：JAPAN SOC INTERNAL MEDICINE

We herein report the case of a leukemia patient who developed hepatitis E seven months after undergoing a transfusion with contaminated blood products. The latency period in this case was significantly longer than that of typical hepatitis E. Recently, chronic infection with hepatitis E virus (HEV) genotype 3 has been reported in immunocompromised patients. There is a possibility that our patient was unable to eliminate the virus due to immunosuppression following chemotherapy and the administration of steroids. The prevalence of HEV in healthy Japanese individuals is relatively high and constitutes a critical source of infection via transfusion. Hepatitis E is an important post-transfusion infection, and immunocompromised patients may exhibit a long latency period before developing the disease.

DOI： 10.2169/internalmedicine.54.2332

Genetic Variants in C5 and Poor Response to Eculizumab 査読

Jun-ichi Nishimura, Masaki Yamamoto, Shin Hayashi, Kazuma Ohyashiki, Kiyoshi Ando, Andres L. Brodsky, Hideyoshi Noji, Kunio Kitamura, Tetsuya Eto, Toru Takahashi, Masayoshi Masuko, Takuro Matsumoto, Yuji Wano, Tsutomu Shichishima, Hirohiko Shibayama, Masakazu Hase, Lan Li, Krista Johnson, Alberto Lazarowski, Paul Tamburini, Johji Inazawa, Taroh Kinoshita, Yuzuru Kanakura

NEW ENGLAND JOURNAL OF MEDICINE 370 ( 7 ) 632 - 639 2014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：MASSACHUSETTS MEDICAL SOC

BackgroundEculizumab is a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement-mediated hemolysis associated with paroxysmal nocturnal hemoglobinuria (PNH). The molecular basis for the poor response to eculizumab in a small population of Japanese patients is unclear.
MethodsWe assessed the sequences of the gene encoding C5 in patients with PNH who had either a good or poor response to eculizumab. We also evaluated the functional properties of C5 as it was encoded in these patients.
ResultsOf 345 Japanese patients with PNH who received eculizumab, 11 patients had a poor response. All 11 had a single missense C5 heterozygous mutation, c.2654GA, which predicts the polymorphism p.Arg885His. The prevalence of this mutation among the patients with PNH (3.2%) was similar to that among healthy Japanese persons (3.5%). This polymorphism was also identified in a Han Chinese population. A patient in Argentina of Asian ancestry who had a poor response had a very similar mutation, c.2653CT, which predicts p.Arg885Cys. Nonmutant and mutant C5 both caused hemolysis in vitro, but only nonmutant C5 bound to and was blocked by eculizumab. In vitro hemolysis due to nonmutant and mutant C5 was completely blocked with the use of N19-8, a monoclonal antibody that binds to a different site on C5 than does eculizumab.
ConclusionsThe functional capacity of C5 variants with mutations at Arg885, together with their failure to undergo blockade by eculizumab, account for the poor response to this agent in patients who carry these mutations. (Funded by Alexion Pharmaceuticals and the Ministry of Health, Labor, and Welfare of Japan.)

DOI： 10.1056/NEJMoa1311084

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

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：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

Ustekinumab Improves Psoriasis without Suppressing Tumor Antigen-Specific Cytotoxic T Lymphocytes 査読

Miwako Narita, Yoshinori Nishizawa, Shunpei Iwaya, Eri Oiwa, Minami Iwabuchi, Takayoshi Uchiyama, Asako Matsuyama, Masayoshi Masuko, Masuhiro Takahashi

INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY 165 ( 1 ) 52 - 60 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：KARGER

Background: Ustekinumab is currently used for the treatment of psoriasis with remarkable efficiency. However, worries about the development of malignancies in ustekinumab- treated patients have not been completely resolved because of the major role of IL-12 and IL-23 in tumor immunity. In the present study, we tried to elucidate the effects of ustekinumab on antigen-specific tumor immunity. Methods: After approval by the institutional ethical committee, a 56-year-old male volunteer with psoriasis was administered with 20 doses of WT1 peptide. WT1-specific cytotoxic T lymphocytes (CTLs) were evaluated by WT1 tetramer assay after mixed lymphocyte peptide culture. Results: WT1 tetramer+ T cells with cytotoxic ability appeared in the blood after peptide administration and the frequency of WT1 tetramer+ T cells increased to more than 15 in 10(6) CD8+ T cells. Thirty months after stopping WT1 administration, the patient commenced treatment with ustekinumab for psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Psoriasis plaques were almost cleared up and the response to ustekinumab has so far lasted for 30 months. The frequency of WT1 tetramer+ T cells has not changed since the initiation of ustekinumab treatment. The effects of ustekinumab on the antigen-presenting and CTL-inducing abilities of dendritic cells were explored in vitro, revealing limited effects on both immune functions. Conclusions: These in vivo/vitro findings imply that ustekinumab improves psoriasis without suppressing tumor antigen-specific CTLs and support the data of recent clinical trials showing no increased incidence of malignancies with ustekinumab treatment. (C) 2014 S. Karger AG, Basel

DOI： 10.1159/000366503

Successful Treatment of Severe Newly Diagnosed Immune Thrombocytopenia Involving an Alveolar Hemorrhage with Combination Therapy Consisting of Romiplostim, Rituximab and Vincristine 査読

Kiyoshi Okazuka, Masayoshi Masuko, Yuji Matsuo, Shukuko Miyakoshi, Tomoyuki Tanaka, Takashi Kozakai, Hironori Kobayashi, Kyoko Fuse, Yasuhiko Shibasaki, Masato Moriyama, Jun Takizawa, Ichiro Fuse, Ken Toba, Tatsuo Furukawa

INTERNAL MEDICINE 52 ( 11 ) 1239 - 1242 2013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

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.

DOI： 10.2169/internalmedicine.52.0080

AMLにおいて地固め療法後のWT1転写産物の減少は予後と関連している(Reduction value of WT1 transcripts after consolidation therapy is associated with prognosis in AML)

Shibasaki Yasuhiko, Seki Yoshinobu, Koyama Satoru, Nikkuni Koji, Nomoto Nobuhiko, Isahai Noriatsu, Kuroha Takashi, Momoi Akihito, Yano Toshio, Ida Tori, Higashimura Masutaka, Kitajima Toshiki, Nanba Ayako, Kobayashi Hironori, Ushiki Takashi, Moriyama Masato, Okazuka Kiyoshi, Masuko Masayoshi, Toba Ken, Furukawa Tasuo

臨床血液 53 ( 9 ) 1179 - 1179 2012年9月

診療参加型臨床実習における骨髄穿刺シミュレーション実習の有用性

鈴木利哉, 増子正義, 古川達雄, 鳥羽健, 奈良信雄

日本内科学会雑誌 101 ( Suppl. ) 200 - 200 2012年2月

Hypocellularity and insufficient expression of angiogenic factors in implanted autologous bone marrow in patients with chronic critical limb ischemia 査読

Masato Oda, Ken Toba, Kiminori Kato, Takuya Ozawa, Takao Yanagawa, Noboru Ikarashi, Tsugumi Takayama, Tomoyasu Suzuki, Haruo Hanawa, Masayoshi Masuko, Hironori Kobayashi, Yoshifusa Aizawa

HEART AND VESSELS 27 ( 1 ) 38 - 45 2012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：SPRINGER

The aim of this study was to identify the clinical parameters of absolutely poor-prognosis patients with chronic critical limb ischemia (AP-CLI). Sixteen no-option CLI patients with arteriosclerosis obliterans: ASO (nine) and non-ASO patients (seven) treated with bone marrow-mononuclear cell implantation (BMI) were analyzed. There were three AP-CLI patients (all ASO). The mRNA expression of several angiogenic factors in the implanted cells was analyzed in comparison with normal donor bone marrow. To observe the response of bone marrow components to hypoxia, normal bone marrow cells were cultured for 24 h in 2.5% O-2, and mRNA expression of angiogenic factors were measured. AP-CLI patients exhibited extraordinary low bone marrow cellularity as well as the percentage of CD34-positive cells. Among angiogenic factors, only VEGF expression was maintained in response to HIF-1, while other factors such as HGF, Ang-1, PLGF, and SDF-1 decreased in the implanted bone marrow cells of the patients with CLI compared to normal bone marrow cells. HIF-1 and all of the five angiogenic factors increased in vitro in response to hypoxia. Thus it is highly likely that angiogenic factors except VEGF do not respond to chronic ischemia in bone marrow in vivo. An organ-protection system against tissue ischemia may be applied for acute hypoxia, but it may be insufficient for chronic ischemia.

DOI： 10.1007/s00380-011-0125-5

腎移植後IgA腎症再発に対し扁摘とステロイドパルス療法後に発症した免疫性血小板減少症(Immune thrombocytopenia)の1例

白野侑子, 星井達彦, 中川由紀, 斎藤和英, 佐藤大輔, 増子正義, 成田一衛, 高橋公太

腎移植・血管外科 23 ( 1 ) 108 - 111 2011年12月

記述言語：日本語出版者・発行元：腎移植・血管外科研究会

腎移植後免疫抑制療法下に発症した免疫性血小板減少症を経験したので報告する。症例は47歳男性、原疾患IgA腎症による慢性腎不全にて生体腎移植を施行した。腎移植2年後肺炎を契機に肉眼的血尿を認めた。翌年、IgA腎症が再発し、扁桃摘出、ステロイドパルス療法にて加療した。翌年、四肢の紫斑の出現と血小板が3000/μlに減少した。骨髄穿刺にて巨核球の増加を認め、諸検査より他の血液疾患を除外した上で免疫性血小板減少症と診断した。ステロイド療法、IVIG、ピロリ菌の除菌療法を施行し、免疫抑制薬は、シクロスポリン(CYA)、ミコフェノール酸モフェチル(MMF)を継続した。入院から13週間後、血小板は増加し7×10^4/μl前後となりその後も再発無く、寛解を維持している。(著者抄録)

Kinetics of pDCs, mDCs, γδT cells and regulatory T cells in association with graft versus host disease after hematopoietic stem cell transplantation. 査読

Watanabe N, Narita M, Furukawa T, Nakamura T, Yamahira A, Masuko M, Toba K, Fuse I, Aizawa Y, Takahashi M

Int J Lab Hematol. 33 ( 4 ) 378 - 390 2011年8月

WT1 peptide vaccination in a CML patient: induction of effective cytotoxic T lymphocytes and significance of peptide administration interval 査読

Anri Saitoh, Miwako Narita, Norihiro Watanabe, Nozomi Tochiki, Akie Yamahira, Takeshi Nakamura, Masami Kaji, Masayoshi Masuko, Tatsuo Furukawa, Ken Toba, Ichiro Fuse, Yoshifusa Aizawa, Masuhiro Takahashi

MEDICAL ONCOLOGY 28 ( 1 ) 219 - 230 2011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：HUMANA PRESS INC

Although antigen-specific immune responses including cytotoxic T cells (CTLs) against antigen peptide could be enhanced after tumor antigen peptide vaccinations, the immune responses do not necessarily result in a decrease or eradication of tumor cells in the vaccination trials. We focused on whether antigen-specific CTLs could be damaged by the repeated stimulation of antigenic peptide and whether regulatory T (Treg) cells would be increased by the administration of WT1 peptide. We administered WT1 peptide 22 times over 18 months in a CML patient who was being treated with imatinib. Although WT1 peptide administration every 2 weeks did not show any beneficial effects on the minimal residual disease (copies of bcr-abl transcripts), the transcripts remarkably decreased to the level of major molecular response after changing the administration interval of WT1 peptide from 2 to 4 weeks. An ex vivo study demonstrated that re-stimulation with WT1 peptide made WT1-specific T cells less reactive to WT1 tetramers and the impaired reactivity of CTLs lasted at least for 1 week. In addition, the cytotoxicity of the T cells was hampered by re-stimulation. Treg cells increased up to more than fivefold at the end of the WT1 administration period. The present findings suggested that the administration of the peptide every 4 weeks is superior to every 2 weeks. In addition, the findings that Treg cells increased gradually in accordance with the duration of WT1 peptide administration revealed the significance of manipulating Treg cells for establishing an efficient tumor antigen peptide vaccination.

DOI： 10.1007/s12032-010-9425-3

Clinical value of assessing the response to imatinib monitored by interphase FISH and RQ-PCR for BCR-ABL in peripheral blood for long-term survival of chronic phase CML patients: results of the Niigata CML-multi-institutional co-operative clinical study 査読

Tatsuo Furukawa, Miwako Narita, Tadashi Koike, Kazue Takai, Koichi Nagai, Masashi Kobayashi, Satoru Koyama, Yoshinobu Seki, Hoyu Takahashi, Masahiro Fujiwara, Kenji Kishi, Koji Nikkuni, Noriatsu Isahai, Wataru Higuchi, Nobuhiko Nomoto, Souichi Maruyama, Masayoshi Masuko, Takashi Kuroha, Takashi Abe, Ken Toba, Masuhiro Takahashi, Yoshifusa Aizawa, Akira Shibata

INTERNATIONAL JOURNAL OF HEMATOLOGY 93 ( 3 ) 336 - 343 2011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：SPRINGER TOKYO

This retrospective analysis investigated the prognostic value of monitoring the response to imatinib using peripheral blood (PB) samples and the impact of the response on outcome in 133 patients with chronic myeloid leukemia (CML). We divided the response into 3 categories according to the results of neutrophil (N)-FISH and BCR-ABL transcript levels in PB; more than a 3-log reduction [major molecular response (MMR)], between a 2-log and 3-log reduction or negative with N-FISH [complete cytogenetic response equivalent (CCyRe)], N-FISH positive or less than a 2-log reduction (non-CCyRe). The median follow-up was 5.46 years. At 5 years, the overall survival (OS) rate and progression-free survival (PFS) rate were 94.4 and 92.0%, respectively. The estimated rate of the CCyRe and MMR were 81.7 and 67.1%, respectively. 106 patients achieving the CCyRe had significantly better OS and PFS than 27 patients without achieving the CCyRe. Patients with MMR had significantly better survival free from death, progression, imatinib withdrawal and a loss of the CCyRe, than patients whose response level remained in the CCyRe without achieving MMR until 18 months. Our observation suggests that the response level of the CCyRe on PB serve as a prognostic indicator, and achieving MMR provides stable long-term survival.

DOI： 10.1007/s12185-011-0774-2