Research Achievements - Other -
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The challenge of achieving treatment-free remission for chronic myeloid leukemia
TAKAHASHI Naoto
Rinsho Ketsueki ( The Japanese Society of Hematology ) 67 ( 2 ) 158 - 164 2026
<p>While tyrosine kinase inhibitors (TKIs) have dramatically improved the prognosis for patients with chronic myeloid leukemia (CML), lifelong therapy presents challenges such as long-term toxicities and financial burden. Consequently, treatment-free remission (TFR) has become a primary therapeutic goal, with the aim of safely discontinuing TKIs while maintaining remission and enhancing patient quality of life (QoL). The feasibility and safety of TFR have been established through numerous clinical trials worldwide. The large-scale J-SKI observational study confirmed a 5-year TFR rate of 65.2% and demonstrated its safety in clinical practice. A sustained period of deep molecular response (DMR) is the most critical predictive factor for a successful TFR attempt. Current challenges include TKI withdrawal syndrome, the success of second TFR attempts, and the rare risk of blast crisis during TFR. Future strategies aim to increase TFR eligibility by achieving higher DMR rates with newer agents.</p>
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The impact of NR1I2 gene polymorphism and body weight on asciminib pharmacokinetics in patients with chronic myeloid leukemia
Naoto Takahashi, Yumiko Akamine, Masatomo Miura
BLOOD 146 2025.11
Summary of the papers read (international conference)
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Kumagai Takuya, Saito Masaya, Sato Takahiko, Inoue Junichi, Ishikawa Norihisa, Ono Tsuyoshi, Kono Michihiro, Takahashi Naoto
Internal Medicine ( 一般社団法人 日本内科学会 ) advpub ( 0 ) 1933 - 1940 2025
<p>We herein report a case of cutaneous squamous cell carcinoma (SCC) characterized by paraneoplastic hypercalcemia-leukocytosis syndrome. The patient presented with systemic symptoms, including anorexia, a fever, and a tumoral lesion on the upper arm. Laboratory test results revealed hypercalcemia and leukocytosis. A tissue biopsy confirmed SCC, and further investigation revealed elevated parathyroid hormone-related protein (PTHrP) and granulocyte-colony stimulating factor (G-CSF) levels. Immunostaining demonstrated G-CSF production by the tumor cells. Radiation therapy was administered, which improved leukocytosis and decreased G-CSF and PTHrP levels. Through a case report and literature review, we explored the clinical characteristics of tumors that produce G-CSF and PTHrP. </p>
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Fujishima Takashi, Kobayashi Takahiro, Kobayashi Isuzu, Kitadate Akihiro, Kameoka Yoshihiro, Takahashi Naoto
Internal Medicine ( 一般社団法人 日本内科学会 ) advpub ( 0 ) 3020 - 3026 2025
<p>We herein present the case of a 73-year-old man with IgM multiple myeloma (IgM-MM) and t(11;14). The tumor cells showed a small lymphoplasmacytic morphology and dim expression of CD38 and CD138. The MYD 88<sup>L265P</sup> mutation was found to be negative. After plasma exchange, bortezomib and dexamethasone treatments were refractory. Subsequent daratumumab, lenalidomide, and dexamethasone therapy failed to respond despite the standard therapy for non-IgM MM. Subsequently, pomalidomide, cyclophosphamide, and dexamethasone therapies demonstrated a good response, and a stringent complete response was therefore achieved. This case highlights the need for different treatment strategies for IgM-MM compared with non-IgM-MM because the biological features of IgM-MM and non-IgM-MM are different. </p>
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Ikeda Sho, Kobayashi Takahiro, Kitadate Akihiro, Yamashita Takaya, Watanabe Atsushi, Fujishima Naohito, Yoshioka Tomoko, Kume Masaaki, Kameoka Yoshihiro, Kitabayashi Atsushi, Kuroki Jun, Takahashi Naoto
Internal Medicine ( 一般社団法人 日本内科学会 ) advpub ( 0 ) 2025
<p><b>Objective </b>In the real-world clinical setting of transplant-eligible patients with multiple myeloma (MM), a certain proportion of patients switch from induction therapy to other regimens because of insufficient response or adverse events. However, the prognostic benefits of these changes remain unclear. This retrospective study investigated the impact of pre-transplant induction therapy switches on the prognosis. </p><p><b>Methods </b>We analyzed the treatment course, patient background, risk classification, and post-transplantation event-free survival (EFS) of 35 patients who achieved partial response (PR) or better with triplet therapy and underwent autologous stem cell transplantation (ASCT) at our institution between January 2017 and July 2023. </p><p><b>Results </b>Induction therapy included VRd therapy in 11 patients and switching therapy in 20 patients (7 due to intolerance and 13 due to insufficient treatment effects). Among the 13 patients who switched treatment due to insufficient treatment effects, 10 showed an improved response, leading to a trend towards a better EFS. Nevertheless, high-risk chromosomal abnormalities, particularly t(4;14), were associated with a significantly poorer EFS, regardless of the treatment received. </p><p><b>Conclusion </b>Even with a response-guided induction treatment switch, maintaining long-term remission after ASCT in high-risk patients remains challenging. A careful risk assessment using fluorescence <i>in situ</i> hybridization or a genomic analysis may improve the prognosis of patients with MM in the future. </p>
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Outpatient treatment of CML using TDM in collaboration with physicians and pharmacists
ABUMIYA Maiko, TAKAHASHI Naoto, MIURA Masatomo
日本血液学会学術集会抄録(Web) 87th 2025
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Pharmacokinetics of asciminib in patients with chronic myeloid leukemia
TAKAHASHI Naoto, MIURA Masatomo
日本血液学会学術集会抄録(Web) 87th 2025
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LINC00887はHDAC3との結合を介して多発性骨髄腫細胞の薬剤耐性を誘導する
長田 直希, 松岡 紗恵, 池田 翔, 高橋 直人, 安井 寛, 古川 雄祐, 菊池 次郎, 仲宗根 秀樹
日本血液学会学術集会 ( (一社)日本血液学会 ) 86回 O1 - 1 2024.10
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SETD7はt(11;14)陽性多発性骨髄腫に対する新たな治療標的分子となる
松岡 紗恵, 長田 直希, 池田 翔, 高橋 直人, 安井 寛, 古川 雄祐, 菊池 次郎, 仲宗根 秀樹
日本血液学会学術集会 ( (一社)日本血液学会 ) 86回 O1 - 4 2024.10
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LINC00887はHDAC3との結合を介して多発性骨髄腫細胞の薬剤耐性を誘導する
長田 直希, 松岡 紗恵, 池田 翔, 高橋 直人, 安井 寛, 古川 雄祐, 菊池 次郎, 仲宗根 秀樹
日本血液学会学術集会 ( (一社)日本血液学会 ) 86回 O1 - 1 2024.10
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SETD7はt(11;14)陽性多発性骨髄腫に対する新たな治療標的分子となる
松岡 紗恵, 長田 直希, 池田 翔, 高橋 直人, 安井 寛, 古川 雄祐, 菊池 次郎, 仲宗根 秀樹
日本血液学会学術集会 ( (一社)日本血液学会 ) 86回 O1 - 4 2024.10
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TFR後の晩期再発は免疫の調節不全を背景にしている
藤岡 優樹, 植木 重治, 高橋 直人
日本血液学会学術集会 ( (一社)日本血液学会 ) 86回 O1 - 5 2024.10
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小児白血病におけるチロシンキナーゼ阻害剤の薬物血中濃度モニタリング
田村 真一, 内藤 優樹, 友安 千紘, 矢野 未央, 三浦 昌朋, 高橋 直人, 石田 宏之
日本血液学会学術集会 ( (一社)日本血液学会 ) 86回 P1 - 6 2024.10
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7. Progress in the Treatment of CML
Takahashi Naoto
Nihon Naika Gakkai Zasshi ( The Japanese Society of Internal Medicine ) 113 ( 9 ) 1732 - 1737 2024.09
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7. Progress in the Treatment of CML
Takahashi Naoto
Nihon Naika Gakkai Zasshi ( The Japanese Society of Internal Medicine ) 113 ( Suppl ) 120a - 120a 2024.02
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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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Kobayashi Takahiro, Honami Sato, Miura Masatomo, Fukushi Yayoi, Kuroki Wataru, Ito Fumiko, Teshima Kazuaki, Watanabe Atsushi, Fujishima Naohito, Kobayashi Isuzu, Kameoka Yoshihiro, Takahashi Naoto
Cancer Chemotherapy and Pharmacology ( Springer Nature ) 2024
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t(4;14)陽性多発性骨髄腫に対するMMSET阻害剤
松岡 紗恵, 菊池 次郎, 長田 直希, 窪田 浩一, 喜久里 貢, 小山 裕雄, 菊地 正樹, 安井 寛, 池田 翔, 高橋 直人, 梅原 崇史, 仲宗根 秀樹, 古川 雄祐
日本血液学会学術集会 ( (一社)日本血液学会 ) 85回 44 - 44 2023.10
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AMLのVEN/AZA治療におけるベネトクラクスの血中濃度と好中球減少症との関連
小林 敬宏, 佐藤 保奈実, 三浦 昌朋, 福司 弥生, 藤田 菜々子, 黒木 航, 伊藤 史子, 手島 和暁, 渡部 敦, 藤島 直仁, 高橋 直人
日本血液学会学術集会 ( (一社)日本血液学会 ) 85回 377 - 377 2023.10
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Acute Myeloid Leukemia Harboring the t(16;21)(p11;q22) Translocation Treated With Venetoclax Plus Azacitidine After Cord Blood Transplantation.
Kazuaki Teshima, Sho Ikeda, Ko Abe, Masahiro Yamada, Naoto Takahashi
Cureus 15 ( 7 ) e42215 2023.07
A 62-year-old female was diagnosed with acute myeloid leukemia (AML) with t(16;21)(p11;q22). She achieved complete hematological remission after induction therapy and underwent umbilical cord blood stem cell transplantation (CBT). At 150 days after the CBT, a bone marrow examination revealed relapse. We treated the patient with venetoclax plus azacitidine as salvage therapy. After five cycles of venetoclax and azacitidine therapy, the patient died due to disease progression. The prognosis of AML with t(16;21)(p11;q22) is very poor owing to the high rate of early relapse even after hematopoietic stem cell transplantation. Therefore, a novel therapeutic approach is required to improve patient outcomes.