Research Achievements - Other -

Cutaneous Squamous Cell Carcinoma Producing Granulocyte Colony-stimulating Factor and Parathyroid Hormone-related Protein: A Case Report and Literature Review

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 )   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>

DOI PubMed CiNii Research

Successful Salvage Therapy with Pomalidomide, Cyclophosphamide, and Dexamethasone for IgM Myeloma with t(11;14) and Dim CD38 Expression Refractory to Daratumumab, Lenalidomide, and Dexamethasone

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 )   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^L265P 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>

DOI CiNii Research

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

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

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

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

DOI CiNii Research

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⁻ 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>

DOI PubMed CiNii Research

Overexposure to venetoclax is associated with prolonged-duration of neutropenia during venetoclax and azacitidine therapy in Japanese patients with acute myeloid leukemia

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

CiNii Research

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

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.

DOI PubMed

c-FOSはIKZF1転写活性化複合体の重要な構成要素であり、多発性骨髄腫におけるレナリドマイド耐性を誘導する(c-FOS is an integral component of the IKZF1 transactivator complex and mediates lenalidomide resistance in multiple myeloma)

長田 直希, 菊池 次郎, 安井 寛, 池田 翔, 松岡 紗恵, 高橋 直人, 古川 雄祐

International Journal of Myeloma ( (一社)日本骨髄腫学会 )  13 ( 3 ) 136 - 136   2023.05

Refractory esophageal stricture of esophageal mucous membrane pemphigoid after allogeneic hematopoietic stem cell transplantation

FUJITA Nanako, YAMASHITA Takaya, ABE Fumito, NARA Miho, YOSHIOKA Tomoko, KOGA Hiroshi, ISHII Norito, TAKAHASHI Naoto

Rinsho Ketsueki ( The Japanese Society of Hematology )  64 ( 2 ) 107 - 112   2023

<p>Haploidentical allogeneic hematopoietic stem cell transplantation from her brother was performed on a 41-year-old lady with no prior history of pemphigoid to treat recurrent AML. On day 59 following transplantation, she experienced esophageal stenosis. During immunosuppressive therapy for graft vs. host disease, this condition was controlled with periodic esophageal dilatation (GVHD). Her esophageal stricture, which required periodic dilatation, grew worse after she stopped immunosuppressive therapy because of recurrent AML. The esophageal mucosa was easily hemorrhagic and desquamative. Histologic analysis revealed that the squamous cell layers had been divided. Indirect immunofluorescence was negative for IgG and positive for IgA on the epidermal layers, while direct immunofluorescence showed a linear deposition of IgG on the basement membrane zone. It was determined through immunoblotting utilizing recombinant protein of BP180 C-terminal domain that both IgG and IgA antibodies were present, supporting the diagnosis of mucous membrane pemphigoid with anti-BP180. After allogeneic transplantation, basal epidermal cell destruction by GVHD may result in autoimmune blistering disorders, which expose basement membrane proteins and antigen presentation. A similar mechanism could apply to our situation. For rare GVHD cases, a thorough histological diagnosis is required.</p>

DOI CiNii Research

Postmortem diagnosis of intravascular large B-cell lymphoma after atraumatic splenic rupture due to splenic infiltration

KUROKI Wataru, KOBAYASHI Takahiro, UMAKOSHI Michinobu, KITADATE Akihiro, IMAIZUMI Chihiro, SAITO Masaya, KOBAYASHI Isuzu, FUJISHIMA Masumi, FUJISHIMA Naohito, YOSHIOKA Tomoko, GOTO Akiteru, TAKAHASHI Naoto

Rinsho Ketsueki ( The Japanese Society of Hematology )  63 ( 6 ) 523 - 529   2022

<p>Atraumatic splenic rupture (ASR) is a rare but fatal complication of malignant lymphoma. However, only one case of intravascular large B-cell lymphoma (IVLBCL)-related ASR (IVLBCL-ASR) has previously been reported, and the mechanism of IVLBCL-ASR is unknown. We present the case of a 78-year-old man who died unexpectedly and was diagnosed with IVLBCL-ASR pathologically by autopsy. A massive intraperitoneal hemorrhage and four lacerations on the splenic surface were discovered during the autopsy. CD20-positive lymphoma cells that infiltrated into small vessels were highly concentrated in the center of the spleen and were only slightly distributed in the lacerations on the splenic surface. Therefore, increased intrasplenic pressure due to lymphoma cell proliferation was identified as the cause of ASR. The patient had undergone ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for tongue cancer evaluation 3 months earlier, and positive uptake was found in the right adrenal gland, where lymphoma cell infiltration was confirmed by the autopsy. Our findings suggest that clinicians should be aware that the advanced stage of IVLBCL can cause fatal ASR via increased intrasplenic pressure. Therefore, early diagnosis and early treatment intervention are desirable to prevent the onset of IVLBCL-ASR, and ¹⁸F-FDG PET/CT is useful for the early diagnosis of IVLBCL.</p>

DOI PubMed CiNii Research

Long-term complete remission of HIV-negative primary testicular plasmablastic lymphoma treated with bortezomib in combination with EPOCH

FUJISHIMA Takashi, KAWABATA Yoshinari, MICHISHITA Yoshihiro, KITABAYASHI Atushi, TAKAHASHI Naoto

Rinsho Ketsueki ( The Japanese Society of Hematology )  63 ( 10 ) 1386 - 1391   2022

<p>Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B-cell lymphoma that is frequently associated with HIV infection or other immunodeficiencies. We present a case of HIV-negative primary testicular PBL with long-term complete remission (CR) and successful treatment with bortezomib in combination with EPOCH (V-EPOCH). Because of rapidly increasing right testicular swelling, an 86-year-old man without immunodeficiencies was admitted to our hospital. Following that, a right high orchiectomy was performed. Histopathological and immunohistochemical analyses revealed diffuse infiltration of plasmablastic lymphocytes, which were positive for CD38, CD138, CD56, MUM1, lambda, EBER, and MYC respectively, but negative for CD20. The MIB-1 index was 90%. FDG abnormal uptake was discovered on PET/CT at systemic lymph nodes. There was no abnormal cell infiltration in either the bone marrow or cerebral spinal fluid. He was diagnosed with PBL, clinical-stage IIIE-A, IPI high-intermediate risk. He achieved durable CR more than 30 months after the diagnosis after six courses of V-EPOCH, followed by intrathecal prophylaxis (IT) and adjuvant radiation therapy (total 30 Gy). Although PBL shows an aggressive clinical course and poor prognosis, adequate therapeutic approaches for PBL have not been established due to the rarity of this disease. According to our findings, V-EPOCH combined with IT and adjuvant radiotherapy appeared to be feasible and effective as a frontline treatment for elderly patients with primary testicular PBL.</p>

DOI PubMed CiNii Research

再発難治性ホジキンリンパ腫に対する免疫チェックポイント阻害薬治療の後方視的解析(Retrospective analysis of ICI therapy for relapsed or refractory classical Hodgkin's lymphoma: THF26)

前田 峻大, 小宅 達郎, 久保 恒明, 高畑 武功, 玉井 佳子, 亀岡 吉弘, 高橋 直人, 宮入 泰郎, 村井 一範, 下瀬川 健二, 吉田 こず恵, 菅原 健, 猪倉 恭子, 福原 規子, 張替 秀郎, 佐藤 諒, 石澤 賢一, 田嶋 克史, 齊藤 宗一, 深津 真彦, 池添 隆之, 角田 三郎, 神林 裕行, 三田 正行, 森 甚一, 古和田 周吾, 伊藤 薫樹

日本血液学会学術集会 ( (一社)日本血液学会 )  83回   OS2 - 2   2021.09

成人初期前駆T細胞性急性リンパ性白血病の臨床的特徴と予後に関する後方視的研究 THF-24(Clinical features and prognosis of adult early T-cell precursor acute lymphoblastic leukemia: THF-24)

古川 瑛次郎, 大西 康, 遠宮 靖雄, 原崎 頼子, 深津 真彦, 池添 隆之, 亀岡 吉弘, 高橋 直人, 八田 俊介, 勝岡 優奈, 濱田 宏之, 村井 一範, 小宅 達郎, 伊藤 薫樹, 甲斐 龍幸, 助川 真純, 中嶌 真治, 柳谷 稜, 石澤 賢一, 山口 公平, 高橋 太郎, 張替 秀郎

日本血液学会学術集会 ( (一社)日本血液学会 )  83回   OS3 - 5   2021.09

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

Domestic Co-author

DOI

Primary breast diffuse large B-cell lymphoma in an elderly man maintaining long-term complete response

NOGUCHI Shinsuke, SAITOH Hirobumi, SASAKI Hideto, KAMATA Shuichi, ENOMOTO Katsuhiko, TAKAHASHI Naoto

Rinsho Ketsueki ( The Japanese Society of Hematology )  62 ( 5 ) 341 - 345   2021

<p>Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare non-Hodgkin's lymphoma that mostly affects women. Here, we report a case of primary breast DLBCL that affected an older man without any autoimmune disease or drug-related female hormones. The patient was a 65-year-old man whose chief complaints were gradually-increasing lump in the right chest and swelling of the right axillary lymph nodes. He was diagnosed with malignant lymphoma through a needle biopsy on suspicion of right breast cancer with right axillary lymph node metastasis. Since the histological type could not be confirmed, right breast mass resection was performed. The patient was referred to our department for treatment because of the diagnoses of primary breast DLBCL, germinal center B-cell type (Hans classification), and clinical stage IIA. In addition to the six courses of R-CHOP therapy, intrathecal injections were used in combination to prevent CNS infiltration. He has been in complete remission for 5 years. Although rare, breast lymphoma can also occur in men; therefore, early histological diagnosis and response to CNS recurrence prevention are important.</p>

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   2020.07  [Refereed]

Domestic Co-author

DOI

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

Ko T.K.

Blood ( Blood )  135 ( 26 ) 2337 - 2353   2020.06  [Refereed]

International Co-author

DOI