Sakurai, Masatoshi

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Hematology) （Shinanomachi）

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)
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Research Areas 【 Display / hide 】

  • Life Science / Hematology and medical oncology

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Research Keywords 【 Display / hide 】

  • hematological malignancies

  • hematopoietic stem cell

  • hematopoietic stem cell transplantation

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Papers 【 Display / hide 】

  • Chemically defined cytokine-free expansion of human haematopoietic stem cells

    Sakurai M., Ishitsuka K., Ito R., Wilkinson A.C., Kimura T., Mizutani E., Nishikii H., Sudo K., Becker H.J., Takemoto H., Sano T., Kataoka K., Takahashi S., Nakamura Y., Kent D.G., Iwama A., Chiba S., Okamoto S., Nakauchi H., Yamazaki S.

    Nature （Nature)  615 （ 7950 ） 127 - 133 2023.03

    ISSN  00280836

    　View Summary

    Haematopoietic stem cells (HSCs) are a rare cell type that reconstitute the entire blood and immune systems after transplantation and can be used as a curative cell therapy for a variety of haematological diseases1,2. However, the low number of HSCs in the body makes both biological analyses and clinical application difficult, and the limited extent to which human HSCs can be expanded ex vivo remains a substantial barrier to the wider and safer therapeutic use of HSC transplantation3. Although various reagents have been tested in attempts to stimulate the expansion of human HSCs, cytokines have long been thought to be essential for supporting HSCs ex vivo4. Here we report the establishment of a culture system that allows the long-term ex vivo expansion of human HSCs, achieved through the complete replacement of exogenous cytokines and albumin with chemical agonists and a caprolactam-based polymer. A phosphoinositide 3-kinase activator, in combination with a thrombopoietin-receptor agonist and the pyrimidoindole derivative UM171, were sufficient to stimulate the expansion of umbilical cord blood HSCs that are capable of serial engraftment in xenotransplantation assays. Ex vivo HSC expansion was further supported by split-clone transplantation assays and single-cell RNA-sequencing analysis. Our chemically defined expansion culture system will help to advance clinical HSC therapies.

  • Clinical characteristics of steroid-responsive but dependent chronic graft-versus-host disease: a multicenter retrospective analysis

    Oyama T., Matsuda K., Honda A., Maki H., Masamoto Y., Murakami D., Toya T., Sakurai M., Kataoka K., Doki N., Kurokawa M.

    International Journal of Hematology （International Journal of Hematology)  117 （ 2 ） 260 - 268 2023.02

    ISSN  09255710

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    Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation. The clinical importance of long-term corticosteroid dependency in steroid-responsive cGVHD is undetermined. We retrospectively reviewed the data of 120 consecutive patients who received systemic steroid therapy for cGVHD between January 2007 and December 2018 at three institutions. Among patients with steroid-responsive cGVHD, those who successfully tapered off corticosteroids within 1 year were defined as the early withdrawal group (EW-cGVHD) and others were defined as the dependent group (Dp-cGVHD). Twenty-six patients were classified as EW-cGVHD and 55 as Dp-cGVHD. The proportion of men was significantly higher and performance status was significantly better in EW-cGVHD. The 5-year overall survival and cGVHD recurrence-free survival rates were significantly higher in EW-cGVHD than Dp-cGVHD (96% vs. 68%, p = 0.017 and 84% vs. 41%, p = 0.002, respectively). While the relapse-free survival rate did not differ significantly (84% vs. 65%, p = 0.15), the proportion of patients requiring readmission, mainly due to cGVHD recurrence or infection, was significantly increased in Dp-cGVHD (38% vs. 84%, p < 0.001). In summary, steroid dependency in cGVHD for more than 1 year was significantly associated with poor transplant outcomes.

  • Concurrent de novo Thymoma-associated Paraneoplastic Type 1 Autoimmune Hepatitis and Pure Red Cell Aplasia after Thymectomy: A Case Report and Literature Review

    Sakata R., Chu P.S., Kawaida M., Emoto K., Sakurai M., Nishida R., Asakura K., Morikawa R., Taniki N., Kataoka K., Kanai T., Nakamoto N.

    Internal Medicine （Internal Medicine)  62 （ 2 ） 243 - 249 2023

    ISSN  09182918

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    The precise manipulation of immune tolerance is the holy grail of immunotherapies for both autoimmunity and cancer immunity. Thymomas are well known to be associated with autoimmune diseases. The exact mechanism by which autoreactivity is induced after thymectomy remains to be elucidated. We herein present the case of a 50-year-old lady with concurrent de novo type 1 autoimmune hepatitis (AIH) and pure red cell aplasia (PRCA), 1 month after undergoing a successful total thymectomy for combined squamous cell carcinoma and thymoma (Masaoka stage II). Corticosteroids yielded short-term effects for both AIH and PRCA. Literature on thymoma-associated AIH, an extremely rare immune-related comorbidity, was also reviewed.

  • Improved survival after single-unit cord blood transplantation using fludarabine and melphalan-based reduced-intensity conditioning for malignant lymphoma: impact of melphalan dose and graft-versus-host disease prophylaxis with mycophenolate mofetil

    Sakatoku K., Kim S.W., Okamura H., Kanaya M., Kato K., Yamasaki S., Uchida N., Kobayashi H., Fukuda T., Takayama N., Ishikawa J., Nakazawa H., Sakurai M., Ikeda T., Kondo T., Yoshioka S., Miyamoto T., Kimura T., Ichinohe T., Atsuta Y., Kondo E.

    Annals of Hematology （Annals of Hematology)  101 （ 12 ） 2743 - 2757 2022.12

    ISSN  09395555

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    We evaluated 413 adult patients with lymphoma who underwent unrelated cord blood transplantation (UCBT) with fludarabine and melphalan (FM)-based reduced-intensity conditioning between 2002 and 2017 to investigate longitudinal changes in outcomes and the optimal melphalan dose and graft-versus-host disease (GVHD) prophylaxis regimen. Outcomes were compared between FM80/100 (melphalan dose: 80 or 100 mg/m2) and FM140 (melphalan dose: 140 mg/m2), as well as between calcineurin inhibitor (CNI) plus methotrexate (MTX), CNI plus mycophenolate mofetil (MMF), and CNI alone. The 3-year overall survival (OS) and non-relapse mortality (NRM) rates improved over time (OS: 27% in 2000s vs. 42% in 2010s, p < 0.001; NRM: 43% in 2000s vs. 26% in 2010s, p < 0.001). Multivariable analysis showed that in the 2000s, melphalan dose and GVHD prophylaxis regimen did not affect any outcomes. In the 2010s, FM80/100 (vs. FM140) related to better OS (hazard ratio [HR] 0.62, p = 0.01) and NRM (HR 0.52, p = 0.016). MTX + CNI and CNI alone (vs. CNI + MMF) related to worse OS (CNI + MTX, HR 2.01, p < 0.001; CNI alone, HR 2.65, p < 0.001) and relapse/progression (CNI + MTX, HR 2.40, p < 0.001; CNI alone, HR 2.13, p = 0.023). In recent years, the use of FM80/100 and CNI + MMF significantly reduced the risk of NRM and relapse/progression, respectively, and resulted in better OS after UCBT for lymphoma.

  • Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation

    Mizuno K., Sakurai M., Kato J., Yamaguchi K., Abe R., Koda Y., Kataoka K., Mori T.

    Transplant Infectious Disease （Transplant Infectious Disease)  24 （ 6 ）  2022.12

    ISSN  13982273

    　View Summary

    Background: Letermovir has been approved as a novel cytomegalovirus (CMV) prophylactic agent after allogeneic hematopoietic stem cell transplantation (HSCT). However, there are still insufficient data to properly evaluate the real-world role of letermovir, and the risk factors for CMV reactivation under letermovir prophylaxis have not been clarified. Methods: We performed a single-institution retrospective analysis of patients under prophylaxis with or without letermovir who underwent allogeneic HSCT between March 2012 and December 2019. In August 2018, letermovir was added to the clinical practice at our institution for the prophylaxis of CMV reactivation in allogeneic HSCT recipients. Patients who underwent HSCT without prophylactic letermovir from March 2012 until September 2018 served as a historical control. Results: The cumulative incidence of clinically significant CMV infection (CS-CMVi) was significantly lower in the letermovir group than in the historical control group not receiving letermovir (30.2% vs. 71.6%, p <.05, at 100 days). In addition, the cumulative incidence of non-relapse mortality (NRM) at day 500 was significantly lower in the letermovir group (4.7% vs. 19.8%, p <.05). We then performed a risk factor analysis for developing CS-CMVi in the letermovir group. The only significant factor identified by this multivariable analysis was transplantation from a CMV seronegative donor to a seropositive recipient (Hazard ratio = 2.76, 95% confidence interval 1.14–6.68, p <.05). Conclusion: Our study showed that letermovir prophylaxis significantly reduced the incidence of CS-CMVi and NRM in a real-world setting and that the CMV serostatus of the donor remained as a risk factor for CS-CMVi even under letermovir prophylaxis.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • Impaired hematopoietic differentiation of iPSCs derived from a patient with FPD/AML.

    櫻井政寿、國本博義、渡邊直英、福地由美、定平健、湯浅慎介、福田恵一、山崎聡、中内啓光、海老原康博、辻浩一郎、伊藤悦朗、原田結花、原田浩徳、岡本真一郎、中島秀明

    第17回造血器腫瘍研究会 (宮崎) , 

    2013
    , 

    Oral presentation (general)

  • 大量 melphalan 療法に伴う嘔気・嘔吐に対する aprepitant の有効性の検討。

    櫻井 政寿、森 毅彦、加藤 淳、山根 明子、小橋 澄子、清水 隆之、岡本 真一郎

    第35回日本造血細胞移植学会 (金沢) , 

    2013
    , 

    Poster presentation

  • 若年者慢性骨髄性白血病患者におけるチロシンキナーゼ阻害薬の治療成績の検討

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    第75回日本血液学会学術集会 (大阪) , 

    2013
    , 

    Oral presentation (general)

  • 国際PNHレジストリにおける日本人患者の特徴

    櫻井政寿、岡本真一郎、臼杵憲祐、西村純一、川口辰哉、二宮治彦、七島勉、岡田昌也、中熊秀喜、中尾眞二、金倉譲

    第75回日本血液学会学術集会 (大阪) , 

    2013

  • 家族性血小板異常症(FPD/AML)における血小板機能異常

    櫻井政寿、渡邊直英、國本博義、福地由美、定平健、阿部大地、相馬俊介、伊藤悦朗、原田結花、原田浩徳、岡本真一郎、中島秀明

    第75回日本血液学会学術集会 (大阪) , 

    2013
    , 

    Oral presentation (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 新たな生体外造血幹細胞培養技術を用いたヒトRUNX1遺伝子の機能解析

    2020.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, INTERNAL MEDICINE (HEMATOLOGY)

    2023

  • INTEGRATION OF BASIC SCIENCE AND CLINICAL MEDICINE

    2023

  • CASE STUDY

    2023

  • LECTURE SERIES, INTERNAL MEDICINE (HEMATOLOGY)

    2022

  • LECTURE SERIES, INTERNAL MEDICINE (HEMATOLOGY)

    2021

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