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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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Kazuaki Kameda, Ryo Yanagiya, Yuji Miyatake, Joaquim Carreras, Hiroshi Higuchi, Hiromichi Murayama, Takashi Ishida, Asahi Ito, Shinsuke Iida, Noriko Fukuhara, Hideo Harigae, Yuki Fujioka, Naoto Takahashi, Hidenori Wada, Fumihiro Ishida, Hideyuki Nakazawa, Rei Ishihara, Yuki Murakami, Hiroyuki Tagawa, Tadashi Matsuura, So Nakagawa, Sadahiro Iwabuchi, Shinichi Hashimoto, Ken-Ichi Imadome, Naoya Nakamura, Kenichi Ishizawa, Yoshinobu Kanda, Kiyoshi Ando, Ai Kotani
Blood ( Blood ) 142 ( 4 ) 352 - 364 2023年07月 [査読有り]
研究論文（学術雑誌）
Aggressive natural killer cell leukemia (ANKL) is a rare lymphoid neoplasm frequently associated with Epstein-Barr virus, with a disastrously poor prognosis. Owing to the lack of samples from patients with ANKL and relevant murine models, comprehensive investigation of its pathogenesis including the tumor microenvironment (TME) has been hindered. Here we established three ANKL-patient-derived xenograft mice (PDXs), which enabled extensive analysis of tumor cells and their TME. ANKL cells primarily engrafted and proliferated in the hepatic sinusoid. Hepatic ANKL cells were characterized by an enriched Myc-pathway and proliferated faster than those in other organs. Interactome analyses and in vivo CRISPR-Cas9 analyses revealed transferrin (Tf)-transferrin receptor 1 (TfR1) axis as a potential molecular interaction between the liver and ANKL. ANKL cells were rather vulnerable to iron deprivation. PPMX-T003, a humanized anti-TfR1 monoclonal antibody, showed remarkable therapeutic efficacy in a preclinical setting using ANKL-PDXs. These findings indicate that the liver, a non-canonical hematopoietic organ in adults, serves as a principal niche for ANKL, and that inhibition of the Tf-TfR1 axis is a promising therapeutic strategy for ANKL.
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Nozaki K, Fujioka Y, Sugiyama D, Ishikawa J, Iida M, Shibata M, Kosugi S, Nishikawa H, Shibayama H.
International Journal of Hematology ( Springer Science and Business Media LLC ) 113 ( 5 ) 772 - 774 2021年05月 [査読有り]
研究論文（学術雑誌）
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Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut.
Kakihana K, Fujioka Y, Suda W, Najima Y, Kuwata G, Sasajima S, Mimura I, Morita H, Sugiyama D, Nishikawa H, Hattori M, Hino Y, Ikegawa S, Yamamoto K, Toya T, Doki N, Koizumi K, Honda K, Ohashi K.
Blood 2016年10月 [査読有り]
研究論文（学術雑誌）
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Transcription factor Gata-3 is essential for lens development
Maeda A, Moriguchi T, Hamada M, Kusakabe M, Fujioka Y, Nakano T, Yoh K, Lim KC, Engel JD, Takahashi S.
Developmentl Dynamics 2009年09月 [査読有り]
研究論文（学術雑誌）
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今月の!検査室への質問に答えます・5 アレルゲン検査で特異的IgE抗体検査と皮膚テストの比較,使い分け,注意点などを教えてください
藤岡 優樹, 嵯峨 亜希子, 植木 重治
臨床検査 ( 株式会社医学書院 ) 67 ( 6 ) 662 - 667 2023年06月
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Endovascular Retrieval of a Fractured Tunneled Hemodialysis Central Venous Catheter Using the Loop Snare Technique.
Tomoko Sasaki, Yuki Fujioka, Haruka Hikichi, Daisuke Yokota, Shigeharu Ueki
Cureus 15 ( 2 ) e35617 2023年02月
The tunneled cuffed hemodialysis catheter is a valuable vascular access option for patients with end-stage renal disease (ESRD). Healthcare providers have become more familiar with the insertion of medical devices, including central venous catheters, in their daily practice. The occurrence of foreign body fragmentation is rare with these catheters. This article presents a case in which a fracture of the distal portion of the hemodialysis catheter was inadvertently identified during a coronary angiography. Percutaneous removal of the fractured venous catheter was performed successfully using a loop snare catheter, which prevented the patient from experiencing further complications.
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免疫応答に着目したCMLにおけるTKI中止後の寛解維持機構の解明とバイオマーカー探索
藤岡優樹, 守時由起, 植木重治, 高橋直人
日本臨床検査医学会誌 ( (一社)日本臨床検査医学会 ) 70 ( 12 ) 944 - 948 2022年12月
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大学検査部の研究紹介 免疫応答に着目したCMLにおけるTKI中止後の寛解維持機構の解明とバイオマーカー探索
藤岡 優樹, 高橋 直人, 守時 由起, 植木 重治
日本臨床検査医学会誌 ( (一社)日本臨床検査医学会 ) 70 ( 11 ) 899 - 899 2022年11月
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単純型血漿交換とリツキシマブが有効であったIgM・IgG型温式抗体を有するEvans症候群
藤田 菜々子, 亀岡 吉弘, 齋藤 綾乃, 齋藤 雅也, 藤岡 優樹, 鵜生川 久美, 奈良 美保, 高橋 直人
臨床血液 ( (一社)日本血液学会-東京事務局 ) 63 ( 11 ) 1590 - 1590 2022年11月
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Galectin-10の測定に関する基礎的検討
藤岡優樹, 山本梨絵, 達子瑠美, 富谷陽子, 守時由起, 植木重治
第70回日本臨床検査医学会学術集会 2023年12月 - 2023年12月
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RCPC1（意識消失のために救急車にて来院した20歳代女性）
常川勝彦, 森本麻衣, 藤岡優樹, 松本剛 [招待有り]
第70回日本臨床検査医学会学術集会 2023年12月 - 2023年12月
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Mechanism of Late Recurrences of Chronic Myeloid Leukemia after Discontinuation of TKI Therapy: BCR::ABL1Ins35bp Loss-of-Function Splicing Mutation and Regulatory T cells
Yuki Fujioka, Junichiro Yuda, Naoto Takahashi
65th ASH Annual Meeting & Exposition 2023年12月 - 2023年12月
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Transient Elevation of Regulatory T cells as a predictive marker of successful TFR after Bostinib Discontinuation
Yuki Fujioka, Takaaki Ono, Naoto Takahashi
24th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy 2023年10月 - 2023年10月
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Kinetics of Treg after TKI discontinuation as a TFR biomarker
Yuki Fujioka, Takaaki Ono, Hiroyoshi Nishikawa, Shigeki Ohtake, Yoshiko Atsuta, Yosuke Minami, Yoshinori Iriyama, Hitoshi Kiyoi, Yasushi Miyazaki, Itaru Matsumura, Naoto Takahashi
第85回日本血液学会 2023年10月 - 2023年10月