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)

 

Research Areas 【 Display / hide

  • Hematology

Research Keywords 【 Display / hide

  • hematological malignancies

  • hematopoietic stem cell

  • hematopoietic stem cell transplantation

 

Papers 【 Display / hide

  • Adoptive cell therapy using tumor-infiltrating lymphocytes for melanoma refractory to immune-checkpoint inhibitors

    Hirai I., Funakoshi T., Kamijuku H., Fukuda K., Mori M., Sakurai M., Koda Y., Kato J., Mori T., Watanabe N., Noji S., Yaguchi T., Iwata T., Ohta S., Fujita T., Tanosaki R., Handa M., Okamoto S., Amagai M., Kawakami Y.

    Cancer Science (Cancer Science)  112 ( 8 ) 3163 - 3172 2021.08

    ISSN  13479032

     View Summary

    To evaluate the feasibility of adoptive cell therapy (ACT) using ex vivo-expanded tumor-infiltrating lymphocytes (TILs) in Japanese patients with melanoma who failed immune-checkpoint inhibitor therapy, an open-label, single-arm, pilot study was conducted. We investigated the immunological and genetic factors of the pretreatment tumor and expanded TILs that may be associated with the clinical response. The treatment protocol comprised preparation of TIL culture, lympho-depleting non-myeloablative preconditioning with cyclophosphamide and fludarabine, TIL infusion, and intravenous administration of low-dose IL-2. Three patients of clinical subtypes mucosal, superficial spreading, and acral melanoma underwent TIL-ACT. Most severe adverse events, including fever and leukopenia, were manageable with the supportive regimen specified in the protocol, suggesting that the TIL-ACT regimen is suitable for Japanese patients with melanoma. One patient showed a short-term partial response, one relatively long-stable disease, and one experienced disease progression. Whole-exome and transcriptional sequencing of isolated tumor cells and immunohistochemical analyses before TIL-ACT revealed various immunostimulatory factors, including a high tumor mutation burden and immune cell-recruiting chemokines, as well as various immunosuppressive factors including TGF-β, VEGF, Wnt/β-catenin, and MAPK signaling and epithelial-to-mesenchymal transition, which might influence the efficacy of TIL-ACT. Our results imply mechanisms for the antitumor effect of and resistance to TIL-ACT. Further studies of immune-resistant mechanisms of TIL-ACT are warranted. This study is registered with the UMIN Clinical Trial Registry (UMIN 000011431).

  • Cytomegalovirus retinitis after allogeneic hematopoietic stem cell transplantation under cytomegalovirus antigenemia-guided active screening

    Mori T., Kikuchi T., Koh M., Koda Y., Yamazaki R., Sakurai M., Tomita Y., Ozawa Y., Kohashi S., Abe R., Saburi M., Kato J.

    Bone Marrow Transplantation (Bone Marrow Transplantation)  56 ( 6 ) 1266 - 1271 2021.06

    ISSN  02683369

     View Summary

    Although cytomegalovirus (CMV) remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), the incidence of CMV retinitis is considered to be lower than the incidence of CMV infection in other organs following allogeneic HSCT. In this study, the incidence and characteristics of CMV retinitis were retrospectively evaluated in recipients of allogeneic HSCT. Ophthalmological screening was performed at the development of ocular symptoms or positive CMV infection using peripheral blood evaluated by pp65 antigenemia or polymerase chain reaction. Of the 514 patients, 13 patients developed CMV retinitis. The median onset of CMV retinitis was day 34 (range, 21–118) post transplant, and the cumulative incidence was 2.5% (95% CI, 1.6–4.2) at 6 months after transplantation. Five patients presented ocular symptoms at the onset. In the remaining eight asymptomatic patients, the diagnosis of CMV retinitis was made by the screening guided by positive CMV infection. All evaluable patients responded to antiviral treatment but three showed incomplete improvement with ocular sequela. Our results suggest that the incidence of CMV retinitis after allogeneic HSCT is not negligible and active ophthalmological screening based not only on symptoms but also positive CMV infection monitoring contributes to the early diagnosis of CMV retinitis.

  • Phase 1 study of plerixafor in combination with total body irradiation-based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation

    Mori T., Kikuchi T., Yamazaki R., Koda Y., Saburi M., Sakurai M., Shigematsu N., Okamoto S., Kato J.

    International Journal of Hematology (International Journal of Hematology)  113 ( 6 ) 877 - 883 2021.06

    ISSN  09255710

     View Summary

    Plerixafor, a CXCR4 inhibitor, has the potential to mobilize leukemic cells, which may contribute to their chemosensitization. This phase 1 study evaluated the safety of myeloablative conditioning combined with plerixafor for allogeneic hematopoietic stem cell transplantation (HSCT). Patients with high-risk leukemia undergoing allogeneic HSCT after total body irradiation (TBI, 12 Gy)-based myeloablative conditioning were eligible; 9 patients were enrolled. The study was performed using a 3 + 3 design with an escalating total dose of plerixafor. Plerixafor was given subcutaneously 8 h before TBI and chemotherapeutic agents. Plerixafor was successfully escalated to the maximum dose (0.72 mg/kg) without dose-limiting toxicities. Underlying diseases were acute myelogenous and lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. As adverse events, plerixafor administration was associated with transient Grades 2–3 diarrhea (n = 7) and abdominal pain (n = 4). In 6 patients, leukemic cell mobilization into the peripheral blood by plerixafor was confirmed by a morphological or molecular method. All patients achieved neutrophil engraftment and 5 were alive in remission at a follow-up after 30–40 months. Plerixafor-combined myeloablative conditioning for allogeneic HSCT was well tolerated. Leukemic-cell mobilization into peripheral blood was observed in half of the patients. Further study is required to evaluate the efficacy and safety of this concept.

  • Toxoplasmosis after allogeneic hematopoietic stem cell transplantation: Impact of serostatus-based management

    Amikura T., Kikuchi T., Kato J., Koda Y., Sakurai M., Yamazaki R., Mikita K., Saburi M., Nakazato T., Mori T.

    Transplant Infectious Disease (Transplant Infectious Disease)  23 ( 3 )  2021.06

    ISSN  13982273

     View Summary

    Toxoplasmosis caused by Toxoplasma gondii (T. gondii) is a serious infectious complication after allogeneic hematopoietic stem cell transplantation (HSCT). The incidence of toxoplasmosis varies widely because of the variabilities of seroprevalence among patient populations. The incidence and the optimal management of toxoplasmosis after allogeneic HSCT in a patient population with a low seroprevalence have not been fully evaluated. We conducted a single-center retrospective study evaluating toxoplasmosis in Japanese patients who underwent allogeneic HSCT. Of the 728 evaluable patients, only 5 developed toxoplasmosis with a median onset of day 60 post-transplant (range, day 55-393). The cumulative incidence was 0.7% (95% CI: 0.3%-1.5%) at day 500 post-transplant. Four of the five patients succumbed due to toxoplasmosis. The more recently treated 220 patients (not the earlier 508 patients) were screened for the T. gondii serostatus, and prophylactic treatment with trimethoprim/sulfamethoxazole was applied. All five patients with toxoplasmosis were in the unscreened group, and there was no case of toxoplasmosis after the introduction of the screening and prophylactic treatment. Our results suggest that toxoplasmosis after allogeneic HST is rare but can develop as a life-threatening complication even in the populations with low seroprevalence, and that prophylactic treatment for seropositive patients could effectively prevent toxoplasmosis.

  • Impact of Specific Antibody Level on Human Herpesvirus 6 Reactivation after Allogeneic Stem Cell Transplantation: H. Nakayama et al

    Nakayama H., Yamazaki R., Kato J., Koda Y., Sakurai M., Mori T.

    Transplantation and Cellular Therapy (Transplantation and Cellular Therapy)  27 ( 2 ) 174.e1 - 174.e5 2021.02

    ISSN  26666367

     View Summary

    The majority of adults are seropositive for human herpesvirus 6 (HHV-6). HHV-6 reactivation can occur after allogeneic hematopoietic stem cell transplantation (HSCT) and lead to life-threatening central nervous system disorders. In this prospective study, we evaluated the relationship between HHV-6 reactivation and anti-HHV-6 IgG antibody levels in recipients of allogeneic HSCT. The HHV-6 viral load in the plasma was quantitatively measured weekly after allogeneic HSCT by real-time polymerase chain reaction. The level of anti-HHV-6 IgG antibody was measured by enzyme‐linked immunosorbent assay before and serially after transplantation. In 28 of the 56 evaluated patients (50%), HHV-6 reactivation was detected after transplantation. In a multivariate analysis, cord blood as the stem cell source was the only significant factor associated with HHV-6 reactivation (odds ratio, 8.6; 95% confidence interval, 2.3 to 32.6; P < .01). When evaluated in the recipients of cord blood transplantation (CBT), the anti-HHV-6 antibody level before transplantation was significantly lower in the patients with HHV-6 reactivation compared with those without (sample positivity index: median, 2.04 [range, 0.95 to 5.98] versus 4.15 [range, 3.93 to 5.65]; P < .05). The anti-HHV-6 antibody level was significantly decreased at 3 months post-transplantation compared with before transplantation (P < .01). Such differences were not observed in other stem cell sources. Our results demonstrate that the low anti-HHV-6 antibody level before transplantation was associated with the reactivation of HHV-6 after CBT, and that the anti-HHV-6 antibody level was significantly decreased specifically after CBT. These results suggest that HHV-6-specific humoral immunity plays a role in HHV-6 reactivation after CBT.

display all >>

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

Reviews, Commentaries, etc. 【 Display / hide

display all >>

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 (general)

  • 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

    >

    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)

display all >>

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, 櫻井 政寿, Grant-in-Aid for Early-Career Scientists , Principal Investigator

 

Courses Taught 【 Display / hide

  • LECTURE SERIES, INTERNAL MEDICINE (HEMATOLOGY)

    2021