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Effects of tucidinostat in adult T-cell leukemia/lymphoma in clinical practice 査読あり
Kamiunten A., Kameda T., Sekine M., Kawano H., Toyama T., Akizuki K., Kawano N., Maeda K., Sato S., Takeuchi M., Ishizaki J., Nagamine K., Kuroki A., Ikeda R., Matsumoto K., Karasawa M., Tahira Y., Uchida T., Shimoda H., Hidaka T., Yamashita K., Yamaguchi H., Kubuki Y., Shimoda K., Shide K.
International Journal of Hematology 2025年
担当区分：筆頭著者 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy with a poor prognosis. We conducted a retrospective study across six institutions in Miyazaki Prefecture, Japan, to assess the efficacy of tucidinostat in patients with relapsed/refractory ATL who had not undergone transplantation. Between October 2021 and July 2023, 24 patients aged 41 to 88 years (median, 73.4 years) who had undergone prior therapies, including intensive chemotherapy (79.2%) and mogamulizumab immunotherapy (79.2%), received tucidinostat. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated as key outcomes. ORR and DCR reached 54.2% and 91.7%, respectively. The median PFS was 3.95 months, and OS was 8.04 months, which were not inferior to the results of a phase IIb study. The influential factors for PFS were age ≥ 75 years and high soluble IL-2 receptor (sIL-2R) levels above 5000 U/mL at the start of treatment. Favorable patients without these factors achieved a PFS of 11.4 months. Treatment-related adverse events were mainly hematologic but were managed over the course of treatment. Our findings indicate that tucidinostat provides survival benefits in patients with relapsed/refractory ATL in clinical practice and highlight key clinical factors for better outcomes.
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Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers 査読あり
Kameda T., Utsunomiya A., Otsuka N., Kubuki Y., Uchida T., Shide K., Kamiunten A., Nakano N., Tokunaga M., Miyazono T., Ito Y., Yonekura K., Kawakita T., Akizuki K., Tahira Y., Karasawa M., Hidaka T., Konagata A., Taniguchi N., Nagatomo Y., Kogo F., Shimizu K., Ueno H., Ishizaki J., Takahashi N., Ikei Y., Hidaka M., Yamaguchi H., Shimoda K.
BMC Infectious Diseases 24 ( 1 ) 2024年12月
掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Infectious Diseases
Background: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown. Methods: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors. Results: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers. Conclusions: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
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Kitamura A., Yanagi S., Shide K., Sato Y., Kamiunten A., Yamanari Y., Kitamura A., Sumiyoshi M., Oda Y., Tsubouchi H., Shimoda K., Miyazaki T.
American Journal of Case Reports 25 2024年
掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Case Reports
Patient: Male, 32-year-old Final Diagnosis: B-acute lymphoblastic leukemia Symptoms: Dyspnea • face swelling Clinical Procedure: — Specialty: Oncology Objective: Unknown etiology Background: Fibrosing mediastinitis (FM) is a rare, fibroproliferative disorder within the mediastinum. It is extremely rare for hematologic malignancies to develop as FM. Case Report: A 32-year-old Japanese man with a 1-month history of headache and 2-week history of facial swelling underwent chest computed tomography (CT); a diffuse mass-like lesion was revealed in the anterior mediastinum with severe stenosis of vital mediastinal organs. After a surgical biopsy, an initial diagnosis of idiopathic FM was made. The FM lesions responded mildly to corticosteroids but recurred repeatedly. Sixteen months after the treatment initiation, blasts appeared in the peripheral blood (PB), and the patient was diagnosed with B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL). Chemotherapy led to complete remission of the B-ALL/LBL and almost complete disappearance of FM-like lesions. Immunohistochemistry of the mediastinal biopsy specimen taken before the blasts’ appearance in PB demonstrated a CD34/CD7/terminal deoxynucleotidyl transferase-positive population, an identical pattern of expression common to the blasts in the patient’s PB and bone marrow. Conclusions: This is the first case report of B-ALL/LBL presenting as FM. This case underscores the importance of considering the possibility of latent hematologic malignancy even in the absence of new symptoms other than those caused by FM lesions for a long period of time. This is the first demonstration that leukemia cells may be present in the FM lesions from the initial stage of disease onset. Even if a diagnosis of idiopathic FM is confirmed, continued suspicion of the presence of hematologic malignancy is vital for improving patient outcomes.
DOI： 10.12659/AJCR.945804
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Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma
Kameda T., Kataoka K., Kamiunten A., Hidaka M., Miyoshi H., Nakano N., Nosaka K., Yoshimitsu M., Yasunaga J.I., Kogure Y., Shide K., Miyahara M., Sakamoto T., Akizuki K., Hidaka T., Kubuki Y., Koya J., Kawano N., Yamashita K., Kawano H., Toyama T., Maeda K., Marutsuka K., Imaizumi Y., Kato K., Sugio T., Tokunaga M., Tashiro Y., Takaori-Kondo A., Miyazaki Y., Akashi K., Ishitsuka K., Matsuoka M., Ohshima K., Watanabe T., Kitanaka A., Utsunomiya A., Ogawa S., Shimoda K.
Haematologica 108 ( 8 ) 2178 - 2191 2023年8月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Haematologica
The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment. In order to identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] =5.46; P<0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR=2.33; P=0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATLPI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3).
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Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma
亀田 拓郎, 片岡 圭亮, 上運天 綾子, 日高 道弘, 三好 寛明, 中野 伸亮, 野坂 生郷, 吉満 誠, 安永 純一朗, 木暮 泰寛, 幣 光太郎, 宮原 正晴, 阪本 貴士, 秋月 渓一, 日髙 智徳, 久冨木 庸子, 古屋 淳史, 河野 徳明, 山下 清, 河野 浩, 外山 孝典, 前田 宏一, 丸塚 浩助, 今泉 芳孝, 加藤 光次, 杉尾 健志, 徳永 雅仁, 田代 幸恵, 髙折 晃史, 宮﨑 泰司, 赤司 浩一, 石塚 賢治, 松岡 雅雄, 大島 孝一, 渡邊 俊樹, 北中 明, 宇都宮 與, 小川 誠司, 下田 和哉
Haematologica 108 ( 8 ) 2178 - 2191 2023年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Ferrata Storti Foundation (Haematologica)
The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. To identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] 5.46, p < 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR 2.33, p = 0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATL-PI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3).
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宮崎県における再発/難治性ATLに対するValemetostat療法の治療効果
上運天 綾子
第10回HTLV1学会学術集会 2024年11月10日
開催年月日： 2024年11月8日 - 2024年11月10日
記述言語：日本語 会議種別：口頭発表（一般）
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Retrospective analysis of hematopoietic stem cell transplantation for ATL in University of Miyazaki
上運天 綾子
第86回日本血液学会学術集会 2024年10月13日
開催年月日： 2024年10月11日 - 2024年10月13日
記述言語：日本語 会議種別：ポスター発表
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日常診療における再発/難治性ATLに対するTucidinostat療法の治療効果
上運天 綾子
第9回HTLV1学会学術集会 2023年11月12日
開催年月日： 2023年11月10日 - 2023年11月12日
記述言語：日本語 会議種別：口頭発表（一般）
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Loss of EZH2 does not affect the severity of murine myeloproliferative neoplasms with CALR mutation
上運天 綾子
第83回日本血液学会学術集会 2021年9月24日
開催年月日： 2021年9月23日 - 2021年9月25日
記述言語：日本語 会議種別：口頭発表（一般）
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Development of MALT1 inhibitor and its effect on ATL
上運天 綾子
第82回日本血液学会学術集会 2020年10月10日
開催年月日： 2020年10月10日 - 2020年11月8日
記述言語：日本語 会議種別：口頭発表（一般）
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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骨髄増殖性腫瘍におけるエピゲノム異常の役割
研究課題/領域番号：19K17834 2019年04月 - 2022年03月
科学研究費補助金 若手研究
担当区分：研究代表者