研究等業績 - その他 - 髙橋　直人

Successful Pregnancies in a Patient with Childhood-onset Steroid-dependent Nephrotic Syndrome during Rituximab Maintenance Therapy.

Mizuho Nara, Hajime Kaga, Masaya Saito, Fumito Abe, Ayano Saito, Chihiro Imaizumi, Atsushi Komatsuda, Hideki Wakui, Naoto Takahashi

Internal medicine (Tokyo, Japan) ( 一般社団法人 日本内科学会 )    2021年03月

There are an increasing number of reports on the safe use of rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, in pregnant women with hematological malignancies or refractory autoimmune diseases. In 2014, the use of RTX for patients with complicated steroid-dependent nephrotic syndrome (SDNS) was approved in Japan. We herein report a woman with childhood-onset complicated SDNS due to focal and segmental glomerulosclerosis, who had two successful pregnancies while receiving RTX maintenance therapy. No adverse complications were observed during the pregnancies, and she delivered healthy newborns. This case suggested that RTX may be used safely in pregnant women complicated with SDNS.

DOI PubMed CiNii Research

脾臓破裂をきたし急速な転帰をとった悪性リンパ腫の1例

馬越 通信, 黒木 航, 小山 慧, 宮部 賢, 浅部 幸紹, 伊藤 行信, 吉田 誠, 高橋 直人, 後藤 明輝

日本病理学会会誌 ( (一社)日本病理学会 )  110 ( 1 ) 353 - 353   2021年03月

Tocilizumab治療中に健常児を得た妊娠中期発症成人Still病

今泉 ちひろ, 阿部 史人, 加賀 一, 齋藤 綾乃, 齋藤 雅也, 奈良 瑞穂, 高橋 直人

日本リウマチ学会北海道・東北支部学術集会抄録集 ( (一社)日本リウマチ学会-北海道・東北支部 )  30回   54 - 54   2021年02月

Correlation between increased immune checkpoint molecule expression and refractoriness to blinatumomab evaluated by longitudinal T cell analysis

Kobayashi T.

International Journal of Hematology ( International Journal of Hematology )    2021年

国内共著

DOI

Long-term treatment-free remission in patients with chronic myeloid leukemia after second-line nilotinib: ENESTop 5-year update

Hughes T.P.

Leukemia ( Leukemia )  35 ( 6 ) 1631 - 1642   2021年

The ENESTop study evaluated treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) in chronic phase who had received ≥3 years of tyrosine kinase inhibitor therapy and achieved sustained deep molecular response only after switching from imatinib to nilotinib. After 1-year nilotinib consolidation, 126 patients attempted TFR. At 48 weeks (primary analysis), 57.9% (73/126) were in TFR. In the present analysis at 5 years, 42.9% (54/126) were in TFR. Since the 48-week analysis, among patients who left the TFR phase, 58% (11/19) did not have a loss of molecular response and discontinued for other reasons. Of the 59 patients who reinitiated nilotinib upon loss of major molecular response (MMR) or confirmed loss of MR4, 98.3% regained MMR, 94.9% regained MR4, and 93.2% regained MR4.5. Overall adverse event rates decreased over the 5 years of TFR. In patients reinitiating nilotinib, there was a cumulative increase in cardiovascular events with longer nilotinib exposure. No disease progression or CML-related deaths were reported. Overall, these results confirm the durability and safety of TFR for patients receiving second-line nilotinib. Cardiovascular risk should be carefully managed, particularly when reinitiating treatment after TFR.

DOI PubMed

Efficacy and safety of ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a case series from a single institute

Kidoguchi K.

International Journal of Hematology ( International Journal of Hematology )    2021年

DOI

長期間完全奏効を維持している高齢男性乳腺原発びまん性大細胞型B細胞リンパ腫

野口 晋佐, 斎藤 宏文, 佐々木 英人, 鎌田 収一, 榎本 克彦, 高橋 直人

臨床血液 ( 一般社団法人 日本血液学会 )  62 ( 5 ) 341 - 345   2021年

<p>乳腺原発びまん性大細胞型B細胞リンパ腫（DLBCL）は稀な非ホジキンリンパ腫であり，殆どは女性に発症する。今回，自己免疫疾患や女性ホルモンの関与がない高齢男性に発症し，長期寛解が得られている胚中心B細胞型乳腺原発DLBCLを経験したので報告する。症例は65歳，男性。徐々に増大する右胸のしこりと右腋窩リンパ節腫脹を主訴として近医を受診した。右乳がんおよび右腋窩リンパ節転移疑いで針生検を行い悪性リンパ腫の診断となった。組織型確定に至らなかったため右乳腺腫瘤摘出術を施行され，乳腺原発DLBCL，胚中心B細胞型（Hans分類），臨床病期IIAの診断となり治療目的で当科紹介となった。R-CHOP療法6コースに加えCNS浸潤予防のため髄腔内注射を併用した。5年間完全寛解を維持している。稀ではあるが男性にも乳腺リンパ腫が生じ得るため組織学的早期診断とCNS再発予防への対応が重要である。</p>

DOI CiNii Research

VEGF-VEGFR2 inhibitor-associated hyaline occlusive glomerular microangiopathy: a Japanese single-center experience

Ozawa M.

Clinical and Experimental Nephrology ( Clinical and Experimental Nephrology )  25 ( 11 ) 1193 - 1202   2021年

Background: Inhibitors of vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling, such as bevacizumab (Bmab), are used for the treatment of various advanced cancers. However, these inhibitors induce renal thrombotic microangiopathy (TMA). Recently, two European cohort studies showed a distinctive histopathological pseudothrombotic pattern different from TMA in Bmab-treated patients. Methods: We analyzed 9 renal biopsies from proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors in our Japanese cohort. Clinical and laboratory features were also assessed in these patients. Results: All 9 patients had moderate to heavy proteinuria with normal or slightly elevated serum creatinine levels. On light microscopy, a patchy pattern of hemispherical/spherical lesions along glomerular capillary walls was a characteristic finding. On immunofluorescence microscopy, staining for immunoglobulins (IgM dominant) at varying intensities was observed mainly along glomerular capillary walls. Especially, hemispherical/spherical positive staining for immunoglobulins was a characteristic pattern. Immunohistochemical studies showed positive staining for immunoglobulins and negative staining for CD61-positive platelets in capillary hemispherical/spherical lesions and positive VEGF staining in podocytes. On electron microscopy, variably electron-dense material in dilated glomerular capillaries and partial effacement of podocyte foot processes were observed. After the withdrawal of VEGF-VEGFR2 inhibitors, proteinuria improved without any specific treatment in 8 patients. Conclusions: Histopathological findings in our patients treated with VEGF-VEGFR2 inhibitors were consistent with those observed in the recently described new form of Bmab-associated hyaline occlusive glomerular microangiopathy. This form should be considered in proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors. Discontinuing VEGF-VEGFR2 inhibitors may lead to improvement of glomerular microangiopathy induced by these drugs.

DOI PubMed

The Combination of Interferon-Alpha and Ponatinib Enables Faster and Deeper Molecular Responses in Patient with De Novo Blast Crisis of CML: Interferon-Alpha May Return as a CML Treatment.

Kunio Hayashi, Kazuhiro Ikegame, Naoto Takahashi

Case reports in hematology   2021   5518727 - 5518727   2021年

In the era of tyrosine kinase inhibitor (TKI) treatment, its effectiveness in treating chronic myelogenous leukemia (CML) has been improved, ensuring the same prognosis as that of healthy people of the same age. However, there are some patients with de novo blast crisis that undergoes acute conversion from the time of diagnosis and does not respond to TKI treatment, especially in the older patients. Here, we present a case of an older patient with de novo lymphoid crisis who was first treated with a combination of TKI and chemotherapy, but it was difficult to maintain a durable deep molecular response (DMR). After he achieved major molecular response (MMR) or less, it was possible to suppress IS% to DMR by performing a combined treatment with interferon-α (IFN-α) and ponatinib. It is considered that DMR can be maintained by the combination of the two-way action of IFN-α, that is, the transfer of dormant CML stem cells to the cellcycle and the activation of a specific immune response to CML cells. This clinical result suggests the possibility of the re-emergence of IFN-α, which has been used a therapeutic drug in the past.

DOI PubMed

Successful salvage therapy of D-PACE combined with pomalidomide in a patient with triple-class refractory secondary plasma cell leukemia(和訳中)

Kobayashi Takahiro, Kuroki Jun, Kobayashi Isuzu, Saito Masaya, Fujishima Masumi, Ubukawa Kumi, Fujishima Naohito, Kameoka Yoshihiro, Nanjo Hiroshi, Takahashi Naoto

International Journal of Myeloma ( (一社)日本骨髄腫学会 )  11 ( 4 ) 27 - 31   2021年

Successful salvage therapy of D-PACE combined with pomalidomide in a patient with triple-class refractory secondary plasma cell leukemia

KOBAYASHI Takahiro, KUROKI Jun, KOBAYASHI Isuzu, SAITO Masaya, FUJISHIMA Masumi, UBUKAWA Kumi, FUJISHIMA Naohito, KAMEOKA Yoshihiro, NANJO Hiroshi, TAKAHASHI Naoto

International Journal of Myeloma ( 一般社団法人 日本骨髄腫学会 )  11 ( 4 ) 27 - 31   2021年

<p>Novel agents have dramatically improved the prognosis of multiple myeloma (MM). However, the prognosis of MM resistant to several classes of novel agents and secondary plasma cell leukemia (sPCL) is poor. In such cases, cisplatin, doxorubicin, cyclophosphamide, and etoposide (PACE)-based regimens are considered in combination with dexamethasone, thalidomide, and bortezomib. Herein, we report the case of a 47-year-old patient with Bence Jones Protein (BJP)-λ-type MM, primary refractory to bortezomib, lenalidomide, and dexamethasone (VRd) therapy, which subsequently progressed to sPCL accompanied with the acquired 17p deletion. Although the patient was also refractory to daratumumab-based therapy (triple-class refractory MM), he was successfully treated with dexamethasone and pomalidomide with PACE (DP-PACE) therapy, and after three cycles, he achieved complete remission (CR) and bridged to allogeneic stem cell transplantation (SCT). To the best of our knowledge, this is the first report of DP-PACE regimen, which may be considered for patients with relapsed refractory MM as a bridge to SCT.</p>

DOI CiNii Research

有毛細胞白血病を疑うリンパ球増多症で発症し,細胞表面解析から診断に至った慢性NK細胞増多症の一例

齊藤由紀子, 小林敬宏, 小林敬宏, 鎌田幸子, 亀岡吉弘, 菊地優子, 永沼綾子, 富谷陽子, 高橋直人, 嵯峨知生, 嵯峨知生, 植木重治, 植木重治

日本検査血液学会雑誌   22   2021年

J-GLOBAL

髄外疾患はヒアルロナン誘導同種親和性骨髄腫細胞-細胞相互作用に由来する【JST・京大機械翻訳】|||

菊池次郎, 小玉信之, 小玉信之, 竹下昌孝, 竹下昌孝, 比島智子, 比島智子, 池田翔, 小林敬宏, 黒田芳明, 内山倫宏, 長田直希, 小山大輔, BOGEN Bjarne, 安井寛, 高橋直人, 三輪哲義, 三輪哲義

日本血液学会学術集会抄録(Web) ( (一社)日本血液学会 )  83rd ( 2 ) OS2 - 1   2021年

J-GLOBAL

腎生検が治療の契機となった慢性リンパ球性白血病

今泉 ちひろ, 齋藤 綾乃, 北舘 明宏, 加賀 一, 齋藤 雅也, 奈良 瑞穂, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  62 ( 6 ) 580 - 580   2020年09月

Pharmacokinetics of dasatinib in a hemodialysis patient with chronic myeloid leukemia and chronic kidney disease

Mori J.

International Journal of Hematology ( International Journal of Hematology )  112 ( 1 ) 115 - 117   2020年07月

国内共著

DOI

Phase 2 study of bosutinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia

Hino M.

International Journal of Hematology ( International Journal of Hematology )  112 ( 1 ) 24 - 32   2020年07月  [査読有り]

国内共著

DOI

Hypereosinophilic syndrome with abundant Charcot-Leyden crystals in spleen and lymph nodes.

Masahide Takeda, Shigeharu Ueki, Yohei Yamamoto, Miho Nara, Mineyo Fukuchi, Katsutoshi Nakayama, Yasufumi Omori, Naoto Takahashi, Makoto Hirokawa

Asia Pacific allergy   10 ( 3 ) e24   2020年07月

Hypereosinophilic syndrome, which is characterized by eosinophilia in the peripheral blood, often causes various organ disorders. Charcot-Leyden crystals are recognized features of various diseases, such as parasite infection and asthma, and are known to be classic hallmarks of eosinophilic inflammation. Our recent study revealed the mechanism of Charcot-Leyden crystal formation (i.e., galectin-10 crystallization), namely the involvement of eosinophil extracellular trap cell death, a nonapoptotic cell death. Here we report an autopsy case of a 57-year-old man who had died of hypereosinophilic syndrome. We found numerous eosinophil extracellular trap cell death-associated Charcot-Leyden crystals in the spleen and lymph nodes. Observation of abdominal lymph nodes by electron microscopy revealed eosinophil extracellular traps and free extracellular granules, which are characteristic of typical eosinophil extracellular trap cell death. In this case, we observed various sizes of Charcot-Leyden crystals that were stained with anti-galectin-10 immunofluorescent staining. Further studies are required to understand the pathophysiological roles of Charcot-Leyden crystals and these may lead to the development of novel therapeutic modalities for severe eosinophilic inflammation.

DOI PubMed

ループス腎炎V型におけるexostosin1(EXT1)/exostosin2(EXT2)の検討

今泉 ちひろ, 阿部 史人, 齋藤 綾乃, 齋藤 雅也, 奈良 瑞穂, 小澤 政豊, 小松田 敦, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  62 ( 4 ) 268 - 268   2020年07月

ループス腎炎V型におけるextosin1(EXT1)/extosin2(EXT2)の検討

今泉 ちひろ, 阿部 史人, 齋藤 綾乃, 齋藤 雅也, 奈良 瑞穂, 小澤 政豊, 小松田 敦, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  62 ( 4 ) 268 - 268   2020年07月

An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia

Ko T.K.

Blood ( Blood )  135 ( 26 ) 2337 - 2353   2020年06月  [査読有り]

国際共著

DOI