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附属病院 第三内科 |
職務経歴（学内） 【 表示 ／ 非表示 】
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2024年04月-継続中
秋田大学 附属病院 第三内科 講師
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2022年04月-2024年03月
秋田大学 附属病院 第三内科 助教
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2020年10月-2022年03月
秋田大学 附属病院 中央検査部 助教
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2020年10月-継続中
秋田大学医学部 血液・腎臓・膠原病内科 医学部附属病院 中央検査部 助教
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2020年04月-2020年09月
市立秋田総合病院 血液内科 医長
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2016年12月-2020年03月
秋田大学医学部 血液・腎臓・膠原病内科 医員
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Phase II clinical trial of lenalidomide and dexamethasone therapy in Japanese elderly patients with newly diagnosed multiple myeloma to determine optimal plasma concentration of lenalidomide
小林 敬宏
Therapeutic Drug Monitoring 2018年09月 [査読有り]
国内共著
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Kogure Y.
Blood ( Blood ) 143 ( 23 ) 2401 - 2413 2024年06月
研究論文（学術雑誌）
It remains elusive how driver mutations, including those detected in circulating tumor DNA (ctDNA), affect prognosis in relapsed/refractory multiple myeloma (RRMM). Here we performed targeted-capture sequencing using bone marrow plasma cells (BMPC) and ctDNA of 261 RRMM cases uniformly treated with ixazomib, lenalidomide, and dexamethasone in a multicenter, prospective, observational study. We detected 24 and 47 recurrently mutated genes in BMPC and ctDNA, respectively. In addition to clonal hematopoiesis-associated mutations, varying proportion of driver mutations, particularly TP53 mutations (59.2% of mutated cases), were present in only ctDNA, suggesting their subclonal origin. In univariable analyses, ctDNA mutations of KRAS, TP53, DIS3, BRAF, NRAS, and ATM were associated with worse progression-free survival (PFS). BMPC mutations of TP53 and KRAS were associated with inferior PFS, while KRAS mutations were prognostically relevant only when detected in both BMPC and ctDNA. A total number of ctDNA mutations in the six relevant genes was a strong prognostic predictor (2-year PFS rates: 57.3%, 22.7%, and 0% for 0, 1, and ≥ 2 mutations, respectively) and independent of clinical factors and plasma DNA concentration. Using the number of ctDNA mutations, plasma DNA concentration, and clinical factors, we developed a prognostic index (ctRRMM-PI), classifying patients into three categories with 2-year PFS rates of 57.9%, 28.6%, and 0%. Serial analysis of ctDNA mutations in 94 cases revealed that TP53 and KRAS mutations frequently emerge after therapy. Thus, we clarify the genetic characteristics and clonal architecture of ctDNA mutations and demonstrate their superiority over BMPC mutations for prognostic prediction in RRMM.
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[Successful cord blood transplantation for refractory gamma-delta hepatosplenic T-cell lymphoma developed during treatment of Crohn's disease].
Akihito Saito, Miho Nara, Takashi Fujishima, Wataru Kuroki, Takaya Yamashita, Takahiro Kobayashi, Sho Ikeda, Akihiro Kitadate, Yoshihiro Kameoka, Naoto Takahashi
[Rinsho ketsueki] The Japanese journal of clinical hematology ( 一般社団法人 日本血液学会 ) 65 ( 1 ) 41 - 46 2024年
研究論文（学術雑誌）
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/l and thrombocytopenia, and contrast-enhanced computed tomography (CT) showed hepatosplenomegaly. Bone marrow biopsy and liver biopsy showed CD4+CD56+TCRγδ＋CD8- 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/l and plt 180,000/µl, so the patient was discharged on day117. HSTCL is a tumor of immature γδT cells with a Vδ1 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 γδ 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.
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Kobayashi T.
Xenobiotica ( Xenobiotica ) 55 ( 1 ) 1 - 6 2024年
研究論文（学術雑誌）
The aim of this study was to investigate the effects of renal function and CYP3A5 polymorphism on the drug interaction between venetoclax and fluconazole in thirty acute myeloid leukaemia patients.The area under the plasma concentration-time curve (AUC) and trough concentration (C0) of venetoclax and the fluconazole C0 were obtained from plasma samples on day 7 later after initiation of venetoclax 200 mg/day combined with fluconazole.The fluconazole C0 values in patients with moderate and severe renal impairment were significantly higher than those in patients with normal or mild impairment (median values 7037, 6234, and 4813 ng/mL, respectively, P = 0.026).In patients with CYP3A5*3/*3 genotype, the AUC0-24 and C0 of venetoclax were not associated with fluconazole C0; however, in patients with a CYP3A5*1 allele, a significant positive correlation was observed between venetoclax C0 and fluconazole C0 (r = 0.782, P = 0.004).The metabolism of venetoclax by CYP3A4 is inhibited even at low fluconazole C0. In patients with a CYP3A5*1 allele, CYP3A5 is inhibited when high fluconazole C0 is induced by renal impairment.The dose of fluconazole for prophylaxis may be 100 mg in patients with severe renal impairment receiving venetoclax therapy.
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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年12月
研究論文（学術雑誌）
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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Iyama S.
Annals of Hematology ( Annals of Hematology ) 104 ( 1 ) 275 - 284 2025年
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Kobayashi T.
Cancer Chemotherapy and Pharmacology ( Cancer Chemotherapy and Pharmacology ) 94 ( 2 ) 285 - 296 2024年08月
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Sato H.
International Journal of Clinical Oncology ( International Journal of Clinical Oncology ) 29 ( 4 ) 481 - 492 2024年04月
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Horigome Y.
Annals of Hematology ( Annals of Hematology ) 103 ( 2 ) 475 - 488 2024年02月
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Fukuda N.
Journal of Chromatographic Science ( Journal of Chromatographic Science ) 62 ( 1 ) 58 - 64 2024年01月
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科研費（文科省・学振）獲得実績 【 表示 ／ 非表示 】
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多発性骨髄腫におけるレナリドミドのNK細胞感受性を決定する要因の探索
若手研究
研究期間: 2020年04月 - 2023年03月 代表者: 小林敬宏
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多発性骨髄腫におけるレナリドミドのNK細胞感受性を決定する要因の探索
若手研究
研究期間: 2020年04月 - 2023年03月 代表者: 小林 敬宏