櫻井　政寿 （サクライ　マサトシ）

Sakurai, Masatoshi

写真a

所属（所属キャンパス）

医学部 内科学教室（血液） （信濃町）

職名

専任講師
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研究分野 【 表示 ／ 非表示 】

  • ライフサイエンス / 血液、腫瘍内科学

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  • 造血器腫瘍

  • 造血幹細胞

  • 造血幹細胞移植

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  • 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年03月

    ISSN  00280836

    　概要を見る

    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年02月

    ISSN  09255710

    　概要を見る

    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年

    ISSN  09182918

    　概要を見る

    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.

  • 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年12月

    ISSN  13982273

    　概要を見る

    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.

  • 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年12月

    ISSN  09395555

    　概要を見る

    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.

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  • Progress in survival following three decades of allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: A real-world registry study in Japan

    Konuma T., Itonaga H., Ishiyama K., Hamamura A., Uchida N., Ozawa Y., Katayama Y., Sakurai M., Ueda Y., Matsuoka K.i., Kawakita T., Eto T., Ara T., Kanda J., Onizuka M., Fukuda T., Atsuta Y.

    American Journal of Hematology （American Journal of Hematology）  98 （ 4 ） E68 - E71 2023年04月

    ISSN  03618609

  • Impact of standard-dose dipeptidyl peptidase-4 inhibitors on the incidence of graft-versus-host disease after allogeneic hematopoietic cell transplantation

    Kimura S.i., Shimizu H., Miyazaki T., Sakurai M., Tanoue S., Kayamori K., Ohwada C., Yoshimura K., Nakasone H., Ohashi T., Shono K., Tachibana T., Hatano K., Okada K., Kimura Y., Seo S., Doki N., Tanaka M., Hatta Y., Takahashi S., Kanda Y.

    Bone Marrow Transplantation （Bone Marrow Transplantation）  58 （ 4 ） 452 - 455 2023年04月

    ISSN  02683369

  • Usefulness of the FilmArray Meningitis/Encephalitis Panel in diagnosis of central nervous system infection after allogeneic hematopoietic stem cell transplantation

    Mori T., Koda Y., Kato J., Sakurai M., Uwamino Y., Hasegawa N.

    Supportive Care in Cancer （Supportive Care in Cancer）  30 （ 1 ） 5 - 8 2021年

    ISSN  09414355

    　概要を見る

    Purpose: The BioFire FilmArray® Meningitis/Encephalitis Panel (FAMEP) is designed to rapidly and accurately detect common multiple pathogens that cause central nervous system (CNS) infection, including viruses, bacteria, and yeast. The FAMEP’s usefulness in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) has not been fully evaluated. This retrospective study evaluated the usefulness of the FAMEP in the screening for CNS infection after allogeneic HSCT. Methods: Cerebrospinal fluid (CSF) was obtained from 12 patients to evaluate the causes of CNS disorders after allogeneic HSCT, and the FAMEP was applied. Results: The median day of the FAMEP evaluations was 27 days post-transplant (range, 0–390). Human herpesvirus 6 (HHV-6) was detected in three patients and cytomegalovirus was detected in one patient, leading to the diagnosis of encephalitis/myelitis. In three patients (HHV-6, n = 2; CMV, n = 1), the presence of the viruses was confirmed by conventional real-time polymerase chain reaction (PCR). However, in the remaining patient with HHV-6 detected by the AMEP, HHV-6 was not detected by real-time PCR at the onset but was detected 7 days later. The treatments for the detected viruses improved the clinical conditions in the four patients. Conclusions: Our results suggest that the FAMEP can be a useful sensitive assay in the screening and diagnosis of CNS viral infections after allogeneic HSCT.

  • Germline RUNX1 translocation in familial platelet disorder with propensity to myeloid malignancies

    Sakurai M., Nannya Y., Yamazaki R., Yamaguchi K., Koda Y., Abe R., Yokoyama K., Ogawa S., Mori T.

    Annals of Hematology （Annals of Hematology）  101 （ 1 ） 237 - 239 2021年

    ISSN  09395555

  • Outcome of allogeneic hematopoietic stem cell transplantation for follicular lymphoma relapsing after autologous transplantation: analysis of the Japan Society for Hematopoietic Cell Transplantation

    Sakurai M., Mori T., Kato K., Kanaya M., Mizuno S., Shiratori S., Wakayama T., Uchida N., Kobayashi H., Kubo K., Amano I., Ohta T., Miyazaki Y., Kanda J., Fukuda T., Atsuta Y., Kondo E., Usui Y., Kato H., Taji H., Mizuno S., Hayashi K., Nawa Y., Hashida R., Hashimoto D., Goto H., Kawata T., Ozeki K., Kuriyama K., Ohbiki M., Imada K., Kako S., Sakamoto K., Kameda K., Yoshimura K., Nitta H., Sekiguchi Y., Takahashi H., Sakai R., Mizuta S., Takamatsu H., Shimizu-Koresawa R., Kataoka K., Hiramoto N., Kamijo K., Nishikubo M., Wada F., Suzumiya J., Aoki K., Watanabe M., Jo T., Toda Y., Shimazu Y., Ago H., Miyazaki K., Aoki T., Kunou S., Izutsu K., Suzuki T., Kim S.W., Yamasaki S., Iida H., Yoshida I., Yokoyama A., Asakura Y., Sakatoku K., Ogawa H., Mitsuhashi K., Okada T., Takahashi T., Suzuki R., Fujimoto A., Ishida F., Ikeda T., Yoshitsugu K., Shiki I., Yano S., Kamiyama Y., Chihara D., Nagata A., Ebihara M., Akihito S., Kaji D., Yamamoto G., Morishima S., Tamura S.

    Bone Marrow Transplantation （Bone Marrow Transplantation）  56 （ 6 ） 1462 - 1466 2021年

    ISSN  02683369

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  • 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年
    , 

    口頭発表（一般）

  • 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年
    , 

    ポスター発表

  • 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

    櫻井政寿、雁金大樹、松木絵里、菊池拓、橋本典諭、小橋澄子、外山高朗、甲田祐也、相馬俊介、阿部大地、笠原秀範、戸澤圭一、加藤淳、清水隆之、森毅彦、宮川義隆、横山健次、中島秀明、岡本真一郎

    第75回日本血液学会学術集会 （大阪） , 

    2013年
    , 

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  • 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年

  • 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年
    , 

    口頭発表（一般）

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 生体外増幅造血幹細胞の定量的評価法の開発

    2024年04月
    -
    2028年03月

    櫻井 政寿, 基盤研究(C), 補助金,  研究代表者

  • 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年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 櫻井 政寿, 若手研究, 補助金,  研究代表者

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  • 慢性期病態学各論

    2024年度

  • 内科学（血液）講義

    2024年度

  • 内科学（血液）講義

    2023年度

  • 基礎臨床統合医学

    2023年度

  • 症例検討

    2023年度

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