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Affiliation |
Graduate School of Medicine Doctorial Course in Medicine Oncoregulatory Medicine Department of Hematology,Nephrology,and Rheumatology |
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Date of Birth |
1964 |
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Laboratory Address |
Dept. Hematology, Akita Univ. |
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Laboratory Phone number |
+81-18-884-6115 |
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Laboratory Fax number |
+81-18-836-2613 |
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Mail Address |
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TAKAHASHI Naoto
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Research Interests 【 display / non-display 】
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血液腫瘍学
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分子細胞遺伝学
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薬物動態
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薬物遺伝学
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血液学
Graduating School 【 display / non-display 】
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-1997
Akita University Graduated
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-1997
Akita University Graduated
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-1990.03
Akita University Faculty of Medicine Graduated
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-1990
Akita University Faculty of Medicine Graduated
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-1990
Akita University Faculty of Medicine School of Medicine Graduated
Graduate School 【 display / non-display 】
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-1997.03
Akita University Graduate School,Division of Medicine Doctor's Course Completed
Studying abroad experiences 【 display / non-display 】
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2003.05-2005.09
Saskatoon Cancer Centre, University of Saskatchewan Postdoctoral Research Fellowship
Campus Career 【 display / non-display 】
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2015.02-Now
Akita University Graduate School of Medicine Doctorial Course in Medicine Oncoregulatory Medicine Professor
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2006.04-2015.01
Akita University School of Medicine School of Medicine Lecturer
External Career 【 display / non-display 】
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2015.02
Akita University Graduate School of Medicine Professor
Research Areas 【 display / non-display 】
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Life Science / Hematology and medical oncology
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Life Science / Hematology and medical oncology
Research Achievements 【 display / non-display 】
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Ponatinib Improved the Prognosis of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Japanese Single-Center Cohort Study.
Nagi Tozawa, Takaya Yamashita, Miho Nara, Yuki Fujioka, Sho Ikeda, Takahiro Kobayashi, Isuzu Kobayashi, Akihiro Kitadate, Yoshihiro Kameoka, Naoto Takahashi
Cureus 15 ( 12 ) e50416 2023.12
Research paper (journal)
Introduction The overall survival (OS) of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has improved with the combination of tyrosine kinase inhibitor (TKI) with intensive chemotherapy. In recent years, there has been increased interest in the possibility of long-term survival without allogeneic hematopoietic stem cell transplantation (HSCT) or maintenance therapy. The aim of this study was to determine the effectiveness of treatment and the resultant outcomes in Ph+ALL patients using real-world data. Methods We performed a single-center retrospective analysis utilizing Akita University Hospital data (Akita, Japan) from November 2000 to June 2023 to evaluate the outcomes of TKI with intensive chemotherapy for Ph+ALL. Results Twenty-three patients with Ph+ALL were treated with intensive chemotherapy combined with TKI, including six imatinib, four dasatinib, and 13 ponatinib. The median patient age was 53 years (range; 28-67). Eighteen patients (78%) achieved complete molecular remission (CMR) within three months. HSCT was performed in 16 patients (70%), all of whom did not receive post-transplant TKI maintenance therapy. Six of the seven patients who did not undergo HSCT received maintenance therapy with ponatinib after intensive chemotherapy. The three-year OS was 81%. Ponatinib treatment resulted in a much higher OS rate than imatinib/dasatinib (100% vs. 60%; P=0.011). CMR within three months was identified as a prognostic factor for molecular relapse-free survival (hazard ratio (HR)=0.22; P=0.027). CD20 positivity was identified as a risk factor for hematological relapse (HR=5.2, P=0.032). Conclusion Even in a single-center cohort study, ponatinib, as a combination TKI with intensive chemotherapy or maintenance therapy, may improve the prognosis of Ph+ALL. Patients with CMR within three months might not necessarily need to receive HSCT, but a subsequent treatment-free status could have been achieved only by HSCT. Furthermore, CD20 positivity may be a useful biomarker for future treatment decisions in patients with Ph+ALL.
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Abumiya M.
Journal of Clinical Pharmacy and Therapeutics ( Journal of Clinical Pharmacy and Therapeutics ) 46 ( 2 ) 382 - 387 2021.04 [Refereed]
Research paper (journal) Domestic Co-author
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Abumiya M.
Journal of Clinical Pharmacy and Therapeutics ( Journal of Clinical Pharmacy and Therapeutics ) 46 ( 1 ) 219 - 222 2021.02 [Refereed]
Research paper (journal) Domestic Co-author
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Ito F.
International Journal of Hematology ( International Journal of Hematology ) 113 ( 1 ) 100 - 105 2021.01 [Refereed]
Research paper (journal) Domestic Co-author
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Teshima Kazuaki, Kume Masaaki, Kondo Rui, Shibata Kenichi, Abe Ko, Aono Hiroaki, Fushimi Susumu, Takahashi Satoshi, Takahashi Satsuki, Saito Masahiro, Takahashi Naoto
Internal Medicine ( 一般社団法人 日本内科学会 ) 2021 [Refereed]
Research paper (journal) Domestic Co-author
<p>A 17-year-old girl was diagnosed with acute lymphoblastic leukemia (ALL). After the administration of high-dose methotrexate (MTX) or intrathecal MTX, the patient experienced transient hemiparesis and motor aphasia. Diffusion-weighted magnetic resonance imaging showed a high-intensity lesion in the bilateral centrum semiovale, and a vasospasm was detected in the proximal segment of bilateral A1 on magnetic resonance angiography. Edaravone was administered, and leucovorin rescue treatment was continued; eventually, the patient's neurological symptoms completely resolved. This finding suggested that vasospasm might be a mechanism underlying MTX-induced transient encephalopathy in adolescent and young adult patients with ALL. </p>
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Successful cord blood transplantation for refractory gamma-delta hepatosplenic T-cell lymphoma developed during treatment of Crohn's disease
SAITO Akihito, NARA Miho, FUJISHIMA Takashi, KUROKI Wataru, YAMASHITA Takaya, KOBAYASHI Takahiro, IKEDA Sho, KITADATE Akihiro, KAMEOKA Yoshihiro, TAKAHASHI Naoto
Rinsho Ketsueki ( The Japanese Society of Hematology ) 65 ( 1 ) 41 - 46 2024
<p>The patient was a 21-year-old man who had been diagnosed with Crohn's disease and received infliximab and azathioprine six years earlier. He was admitted with fever and fatigue. Peripheral blood examination showed LDH 2,473 U/<i>l</i> and thrombocytopenia, and contrast-enhanced computed tomography (CT) showed hepatosplenomegaly. Bone marrow biopsy and liver biopsy showed CD4+CD56+TCR<i>γδ</i>+CD8<sup>−</sup> atypical cells, leading to a diagnosis of hepatosplenic T-cell lymphoma (HSTCL). The patient was refractory to CHOP and DA-EPOCH, and therefore received cord blood transplantation with myeloablative conditioning. CT showed reduced in hepatosplenomegaly and peripheral blood examination showed LDH 165 U/<i>l</i> and plt 180,000/µ<i>l</i>, so the patient was discharged on day117. HSTCL is a tumor of immature <i>γδ</i>T cells with a V<i>δ</i>1 mutation in the spleen, and immunodeficiency has been implicated in its pathogenesis. Patients with inflammatory bowel disease treated with azathioprine are known to have an increased risk of lymphoproliferative disease. In this case, use of immunosuppressive drugs for Crohn's disease may have caused malignant transformation of <i>γδ</i> cells in the intestinal epithelium. Although the patient was refractory to chemotherapy, he was able to achieve remission with early cord blood transplantation and long-term survival is expected.</p>
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Refractory esophageal stricture of esophageal mucous membrane pemphigoid after allogeneic hematopoietic stem cell transplantation
FUJITA Nanako, YAMASHITA Takaya, ABE Fumito, NARA Miho, YOSHIOKA Tomoko, KOGA Hiroshi, ISHII Norito, TAKAHASHI Naoto
Rinsho Ketsueki ( The Japanese Society of Hematology ) 64 ( 2 ) 107 - 112 2023
<p>Haploidentical allogeneic hematopoietic stem cell transplantation from her brother was performed on a 41-year-old lady with no prior history of pemphigoid to treat recurrent AML. On day 59 following transplantation, she experienced esophageal stenosis. During immunosuppressive therapy for graft vs. host disease, this condition was controlled with periodic esophageal dilatation (GVHD). Her esophageal stricture, which required periodic dilatation, grew worse after she stopped immunosuppressive therapy because of recurrent AML. The esophageal mucosa was easily hemorrhagic and desquamative. Histologic analysis revealed that the squamous cell layers had been divided. Indirect immunofluorescence was negative for IgG and positive for IgA on the epidermal layers, while direct immunofluorescence showed a linear deposition of IgG on the basement membrane zone. It was determined through immunoblotting utilizing recombinant protein of BP180 C-terminal domain that both IgG and IgA antibodies were present, supporting the diagnosis of mucous membrane pemphigoid with anti-BP180. After allogeneic transplantation, basal epidermal cell destruction by GVHD may result in autoimmune blistering disorders, which expose basement membrane proteins and antigen presentation. A similar mechanism could apply to our situation. For rare GVHD cases, a thorough histological diagnosis is required.</p>
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KUROKI Wataru, KOBAYASHI Takahiro, UMAKOSHI Michinobu, KITADATE Akihiro, IMAIZUMI Chihiro, SAITO Masaya, KOBAYASHI Isuzu, FUJISHIMA Masumi, FUJISHIMA Naohito, YOSHIOKA Tomoko, GOTO Akiteru, TAKAHASHI Naoto
Rinsho Ketsueki ( The Japanese Society of Hematology ) 63 ( 6 ) 523 - 529 2022
<p>Atraumatic splenic rupture (ASR) is a rare but fatal complication of malignant lymphoma. However, only one case of intravascular large B-cell lymphoma (IVLBCL)-related ASR (IVLBCL-ASR) has previously been reported, and the mechanism of IVLBCL-ASR is unknown. We present the case of a 78-year-old man who died unexpectedly and was diagnosed with IVLBCL-ASR pathologically by autopsy. A massive intraperitoneal hemorrhage and four lacerations on the splenic surface were discovered during the autopsy. CD20-positive lymphoma cells that infiltrated into small vessels were highly concentrated in the center of the spleen and were only slightly distributed in the lacerations on the splenic surface. Therefore, increased intrasplenic pressure due to lymphoma cell proliferation was identified as the cause of ASR. The patient had undergone <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography (<sup>18</sup>F-FDG PET/CT) for tongue cancer evaluation 3 months earlier, and positive uptake was found in the right adrenal gland, where lymphoma cell infiltration was confirmed by the autopsy. Our findings suggest that clinicians should be aware that the advanced stage of IVLBCL can cause fatal ASR via increased intrasplenic pressure. Therefore, early diagnosis and early treatment intervention are desirable to prevent the onset of IVLBCL-ASR, and <sup>18</sup>F-FDG PET/CT is useful for the early diagnosis of IVLBCL.</p>
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Long-term complete remission of HIV-negative primary testicular plasmablastic lymphoma treated with bortezomib in combination with EPOCH
FUJISHIMA Takashi, KAWABATA Yoshinari, MICHISHITA Yoshihiro, KITABAYASHI Atushi, TAKAHASHI Naoto
Rinsho Ketsueki ( The Japanese Society of Hematology ) 63 ( 10 ) 1386 - 1391 2022
<p>Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B-cell lymphoma that is frequently associated with HIV infection or other immunodeficiencies. We present a case of HIV-negative primary testicular PBL with long-term complete remission (CR) and successful treatment with bortezomib in combination with EPOCH (V-EPOCH). Because of rapidly increasing right testicular swelling, an 86-year-old man without immunodeficiencies was admitted to our hospital. Following that, a right high orchiectomy was performed. Histopathological and immunohistochemical analyses revealed diffuse infiltration of plasmablastic lymphocytes, which were positive for CD38, CD138, CD56, MUM1, lambda, EBER, and MYC respectively, but negative for CD20. The MIB-1 index was 90%. FDG abnormal uptake was discovered on PET/CT at systemic lymph nodes. There was no abnormal cell infiltration in either the bone marrow or cerebral spinal fluid. He was diagnosed with PBL, clinical-stage IIIE-A, IPI high-intermediate risk. He achieved durable CR more than 30 months after the diagnosis after six courses of V-EPOCH, followed by intrathecal prophylaxis (IT) and adjuvant radiation therapy (total 30 Gy). Although PBL shows an aggressive clinical course and poor prognosis, adequate therapeutic approaches for PBL have not been established due to the rarity of this disease. According to our findings, V-EPOCH combined with IT and adjuvant radiotherapy appeared to be feasible and effective as a frontline treatment for elderly patients with primary testicular PBL.</p>
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Kobayashi T.
International Journal of Hematology ( International Journal of Hematology ) 2021
Domestic Co-author
◆Original paper【 display / non-display 】
◆Other【 display / non-display 】
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Grant-in-Aid for Scientific Research(C)
Project Year： 2018.04 - 2022.03
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The mechanism of organelle relocation in human erythroblasts.
Grant-in-Aid for Scientific Research(C)
Project Year： 2018.04 - 2022.03 Investigator(s): Ubukawa Kumi
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Grant-in-Aid for Scientific Research(C)
Project Year： 2014.04 - 2018.03
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Do patients taking tacrolimus need to undergo CYP3A5 genotyping along with blood concentration monitoring?
Grant-in-Aid for Scientific Research(C)
Project Year： 2014.04 - 2018.03 Investigator(s): Niioka Takenori, MIURA Masatomo, SATOH Shigeru, TAKAHASHI Naoto, KAGAYA Hideaki
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Development of a new treatment strategy using TDM for next generation anticancer drug
Grant-in-Aid for Scientific Research(C)
Project Year： 2014.04 - 2017.03 Investigator(s): Miura Masatomo, Takahashi Naoto, Shibata Hiroyuki, Tsuchiya Norihiko, Kagaya Hideaki, Abumiya Maiko
Acceptance of contract business 【 display / non-display 】
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Contract period： 2020.04.01 - 2021.03.31
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Contract period： 2020.04.01 - 2021.03.31
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Contract period： 2020.04.01 - 2021.03.31