研究等業績 - その他 - 髙橋　直人

Asciminib demonstrates superior efficacy and safety in newly diagnosed chronic myeloid leukemia in the ASC4FIRST trial

Cortes J.E.

Blood ( Blood )  147 ( 13 ) 1433 - 1446   2026年03月

DOI

Five-year interim analysis of J-SKI: an observational study of TKI discontinuation in patients with CML in Japan

Takahashi N.

International Journal of Hematology ( International Journal of Hematology )    2026年

DOI

慢性骨髄性白血病におけるtreatment-free remissionへの挑戦

髙橋 直人

臨床血液 ( 一般社団法人 日本血液学会 )  67 ( 2 ) 158 - 164   2026年

<p>チロシンキナーゼ阻害薬（TKI）は慢性骨髄性白血病（CML）の予後を著しく改善したが，生涯にわたる内服は晩期の血管事象や経済的毒性といった課題を伴う。このため，TKIを安全に中止し寛解を維持する無治療寛解（treatment-free remission, TFR）は，患者のQoLを改善する重要な治療ゴールとして位置づけられている。国内外の多くの臨床試験によりTFRの安全性と有効性が確立されており，大規模観察研究J-SKIの中間解析では5年TFR率65.2％と良好で，TKI中止前の深い分子遺伝学的寛解（DMR）の期間が成功の鍵であることが示された。課題としては，TKI離脱症候群や，2回目のTFRの挑戦，ごく稀な急性転化リスクが挙げられる。今後，新規薬剤を用いてより多くの患者がDMRを達成し，TFRに挑戦できる機会を増やすことが期待される。</p>

DOI PubMed CiNii Research

Progression of diabetic nephropathy and adverse renal outcomes: possible involvement of Toll-like receptor 4 expression

Saito A.

Clinical and Experimental Nephrology ( Clinical and Experimental Nephrology )    2026年

DOI

Comparative analysis of necrotizing enterocolitis in preterm infants born in Japan and born to mothers of Japanese ethnicity in California

Kusuda S.

Scientific Reports ( Scientific Reports )  15 ( 1 )   2025年12月

DOI

Distal renal tubular acidosis triggered by clozapine in a patient with a heterozygous ATP6V0A4 c.1029 + 5G > A variant: a case report and literature review

Kumagai T.

BMC Nephrology ( BMC Nephrology )  26 ( 1 )   2025年12月

DOI

Development and Validation of a Novel High-Performance Liquid Chromatography Assay with Ultraviolet Detection for Determination of Asciminib in Human Plasma

Miura M.

Journal of Chromatographic Science ( Journal of Chromatographic Science )  63 ( 10 )   2025年11月

A rapid, simple and highly sensitive stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated for the estimation of asciminib in human plasma. Plasma samples (100 μL) were processed by solid-phase extraction. Chromatographic separation was performed using a CAPCELL PAK C18 MGII column (4.6 × 250 mm, 5 μm); the mobile phase consisted of 0.5% potassium dihydrogen phosphate (KH2PO4, pH 3.5): acetonitrile: methanol (50:45:5, v/v/v) at a flow rate of 0.5 mL/min. Detection was carried out at a wavelength of 250 nm. The developed method showed good linearity over the concentration range of 10-5000 ng/mL (correlation coefficient: 0.9999). The method was then validated according to guidelines published by the US Food and Drug Administration. The coefficients of variation for intra- and interday assays for asciminib were less than 13.9%, whereas accuracies for intra- and interday assays were within 8.9%. The limit of quantification was 10 ng/mL. The mean (minimum - maximum) plasma trough concentration of asciminib in 29 Japanese patients with chronic myeloid leukemia who received repeated administration of 40 mg twice daily was 367 (101-807) ng/mL. The validated method can be used as a routine method to support pharmacokinetic studies of asciminib.

DOI PubMed

Emotion Recognition Using Temporal Facial Skin Temperature and Eye-Opening Degree During Digital Content Viewing for Japanese Older Adults

Tanabe R.

Sensors ( Sensors )  25 ( 21 )   2025年11月

DOI

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年11月

研究発表要旨（国際会議）  

DOI

ESTIMATION OF EMOTIONAL AROUSAL IN OLDER ADULTS DURING ESPORTS: A MACHINE LEARNING APPROACH FOCUSED ON FACIAL SKIN TEMPERATURE AND BODY MOVEMENT CHANGES

Kikuchi R.

International Journal of Innovative Computing Information and Control ( International Journal of Innovative Computing Information and Control )  21 ( 5 ) 1167 - 1185   2025年10月

DOI

Feature Analysis of Facial Color Information During Emotional Arousal in Japanese Older Adults Playing eSports

Kikuchi R.

Sensors ( Sensors )  25 ( 18 )   2025年09月

DOI

Improving chronic myeloid leukemia management and quality of life: Patient and physician survey on unmet needs from the CML SUN survey

Lang F.

Haematologica ( Haematologica )  111 ( 2 ) 597 - 608   2025年07月

DOI

Bosutinib for Successful Treatment-Free Remission in Chronic Myeloid Leukemia

Fujioka Y.

Cancer Medicine ( Cancer Medicine )  14 ( 9 )   2025年05月

DOI

症例からひもとく疾患 慢性骨髄性白血病

藤岡 優樹, 永沼 綾子, 齊藤 由紀子, 植木 重治, 高橋 直人

検査と技術 ( (株)医学書院 )  53 ( 4 ) 446 - 452   2025年04月

c-FOS Confers Stem Cell-like Features to Multiple Myeloma Cells in a Bone Marrow Microenvironment

Osada N.

Cells ( Cells )  14 ( 7 ) 474 - 474   2025年04月

Multiple myeloma (MM) is the second most common hematologic malignancy and has a poor prognosis. Although the outcomes of MM have markedly improved with the approval of novel agents, the high incidence of relapse means that MM remains incurable. The bone marrow microenvironment (BMME) contributes to drug resistance and minimal residual disease (MRD), which is a major source of relapse in patients with MM. However, the underlying molecular mechanisms are not fully understood. We have previously shown that the upregulation of the AP-1 transcription factor c-FOS confers lenalidomide resistance by maintaining IRF4 expression in MM cells. In this study, we show that upregulated expression of c-FOS confers a poor prognosis and cancer stem cell-like features, including drug resistance, within BMME, both in vitro and in vivo, via IRF4 upregulation; and that inhibition of c-FOS by the AP-1 inhibitor, T-5224, prevents regeneration of MM cells via IRF4 downregulation in a murine serial transplantation assay. These results suggest a functional role for c-FOS in conferring cancer stem cell-like features to MM cells in the BMME for the first time. Therefore, c-FOS inhibition may be an effective treatment strategy for improving the outcomes of patients with MM by eliminating drug-resistant cancer stem cell-like MM cells in MRD.

DOI

症例からひもとく疾患 慢性骨髄性白血病

藤岡 優樹, 永沼 綾子, 齊藤 由紀子, 植木 重治, 髙橋 直人

検査と技術 ( 株式会社医学書院 )  53 ( 4 ) 446 - 452   2025年04月

DOI CiNii Research

Abstract Versus Concrete Risk Identification in Clinical Research in Japan: Randomized and Prospective Pilot Research on the Effect of Risk Reduction Activities in a Risk-Based Approach

Kondo H.

Therapeutic Innovation and Regulatory Science ( Therapeutic Innovation and Regulatory Science )  59 ( 1 ) 71 - 79   2025年01月

DOI

Outcomes of pregnancy in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitors

Kondo T.

Cancer ( Cancer )  131 ( 1 ) e35611   2025年01月

BACKGROUND: Young female patients with chronic myeloid leukemia (CML) often face challenges becoming pregnant due to the teratogenicity of tyrosine kinase inhibitors (TKIs). METHODS: The authors conducted a nationwide survey of female patients with CML who experienced pregnancy between 2002 and 2020. RESULTS: Information for 70 pregnancies in 49 patients was obtained. There were three types of pregnancies: CML onset during pregnancy (n = 9), unplanned pregnancy mostly during treatment with a TKI (n = 25), and planned pregnancy during treatment-free remission (TFR) or treatment with interferon-alpha (IFN-α) (n = 36). The median duration from CML diagnosis to pregnancy in patients with planned pregnancy was significantly longer than that in patients with unplanned pregnancy (10.6 years vs. 4.1 years, p < .001). In 48 pregnancies that resulted in childbirth, TFR and treatment with IFN-α were chosen in 26 and 17 pregnancies, respectively. Sustained major or deeper molecular response was observed in 18 of 26 pregnancies with TFR. The patients who fulfilled the requirements for TKI therapy discontinuation by European LeukemiaNet recommendations achieved a TFR rate of 77% in pregnancy. Treatment with IFN-α might be effective for patients who are in complete cytogenetic response or deeper response (response rate, 76%). CONCLUSION: Pregnancy by TFR or treatment with IFN-α could be a safe and feasible way for patients with CML. However, a substantial duration of treatment with a TKI before conception may be needed for planned pregnancy. Planning and evaluation for pregnancy should be considered at the time of CML onset for female patients with childbearing potential.

DOI PubMed

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 ) 1933 - 1940   2025年

<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

Asciminib in patients with newly diagnosed chronic myeloid leukemia: results from the Japanese subgroup of ASC4FIRST

Takahashi N.

International Journal of Hematology ( International Journal of Hematology )  122 ( 5 ) 647 - 659   2025年

INTRODUCTION: The phase III ASC4FIRST study (NCT04971226) demonstrated superior efficacy and favorable safety and tolerability for asciminib against investigator-selected tyrosine kinase inhibitors (IS-TKI) in newly diagnosed chronic myeloid leukemia (CML). Results of a subgroup analysis in Japanese patients are presented here. METHODS: Adult patients were randomized 1:1 to asciminib or IS-TKI following stratification by European Treatment and Outcome Study long-term survival risk score and prerandomization-selected TKI (imatinib and second-generation [2G] TKI strata). At week 48, major molecular response (MMR) rate in all patients and imatinib stratum (primary endpoints) were assessed along with MR4.0, MR4.5, and safety (cutoff: November 28, 2023). RESULTS: In Japanese patients (asciminib, n = 21; IS-TKI, n = 17 [imatinib/2G TKI, n = 8/9]), the MMR rate was higher with asciminib (81.0%) than IS-TKI (47.1%), and versus imatinib (asciminib: 100%; imatinib: 25.0% [imatinib stratum]). More patients on asciminib than IS-TKI achieved MR4.0 (57.1% vs. 11.8%) and MR4.5 (28.6% vs. 5.9%). Fewer grade ≥ 3 adverse events (AEs; 42.9%, 50.0%, and 55.6%) and AEs leading to treatment discontinuation (0%, 37.5%, and 11.1%) occurred with asciminib than imatinib or 2G TKI. CONCLUSION: Outcomes in Japanese patients were consistent with the ASC4FIRST overall population. Asciminib may be a therapy of choice for Japanese patients with CML.

DOI PubMed

Multiple myeloma with 1q gain/amplification exhibits reduced CD38 expression via interleukin-6 receptor overexpression

Kuroki W.

British Journal of Haematology ( British Journal of Haematology )  206 ( 6 ) 1615 - 1626   2025年

Multiple myeloma (MM) with chromosome 1q21 gain/amplification (1q+) has been reported to respond poorly to daratumumab. We aimed to explore the mechanism of daratumumab resistance in 1q+ MM. Our findings revealed significantly lower CD38 expression in patients with 1q+ MM than in those with 1q wild type (WT) MM. Next, we focused on the interleukin-6 receptor (IL6R) located in the 1q21 region because a previous report shows that interleukin-6 (IL-6) reduces CD38 expression via the IL-6/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway activation in MM. Indeed, IL6R expression was significantly higher in 1q+ MM than in 1q WT MM. We verified that the 1q+ human myeloma cell lines (HMCLs) expressed higher IL6R levels than the 1q WT HMCLs. IL-6 treatment induced CD38 downregulation in both the 1q+ HMCLs and primary bone marrow (BM) samples but not in their 1q WT HMCLs and BM samples. IL-6 also resulted in the upregulation of phosphorylated STAT3 in 1q+ HMCLs but not in the 1q WT HMCLs. Furthermore, inhibition of the IL-6/JAK/STAT pathway by treatment with ruxolitinib or tocilizumab restored CD38 expression in the 1q+ HMCLs and BM samples. These findings elucidate the mechanisms underlying daratumumab resistance in 1q+ MM and provide insights for future therapeutic strategies.

DOI PubMed

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 ) 3020 - 3026   2025年

<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 PubMed CiNii Research

Clinical Practice of Treatment Switch in Transplant-eligible Patients with Multiple Myeloma: An Exploratory Retrospective Analysis

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 ) 1106 - 1114   2025年

<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>

DOI PubMed CiNii Research

Dismal Outcome of EBV-Positive Nodal T/NK-Cell Lymphoma: A Multicenter Retrospective Study

Ichikawa S.

Clinical Lymphoma Myeloma and Leukemia ( Clinical Lymphoma Myeloma and Leukemia )  26 ( 3 ) e376 - e384   2025年

DOI

NF-κB Is a Potential Therapeutic Target for Histone Deacetylase Inhibitor-Resistant Cutaneous T-Cell Lymphoma

Takahashi Y.

Cancer Science ( Cancer Science )  117 ( 2 ) 407 - 417   2025年

Histone deacetylase inhibitors, such as vorinostat, show promise as treatment for T-cell lymphomas including cutaneous T-cell lymphoma. However, the emergence of resistance ultimately leads to disease relapse. To elucidate the underlying mechanisms and identify potential countermeasures, we established histone deacetylase inhibitor-resistant cutaneous T-cell lymphoma cell lines by prolonged exposure to vorinostat. We then comprehensively profiled gene expression in these cell lines by using microarrays and in silico analytical approaches. We identified 83 genes that were significantly upregulated in the resistant cell lines. Subsequent enrichment analyses using ChIP-Atlas and Enrichr revealed that these genes are regulated by particular transcription factors, including RELA/p65, GATA3, and EP300, of which RELA (p65) exhibited the highest composite score. RELA is a key subunit of the NF-κB complex, which is involved in inflammation, cell survival, and proliferation. We demonstrated marked upregulation and nuclear enrichment of p65 and pronounced NF-κB pathway activation in the histone deacetylase inhibitor-resistant cells. The mechanism involved acetylation-mediated inhibition of p65 ubiquitination, which resulted in protein stabilization and enhanced transcriptional activity. Histone deacetylase inhibitor-resistant cell lines displayed heightened sensitivity to inhibition of the NF-κB pathway by bortezomib and dimethyl fumarate. These findings implicate aberrant NF-κB activation as a central driver of the emergence of histone deacetylase inhibitor resistance in cutaneous T-cell lymphoma. Ultimately, our results provide a strong rationale for exploring NF-κB inhibition as a therapeutic strategy to restore or enhance the efficacy of histone deacetylase inhibitor-based therapies, overcome histone deacetylase inhibitor resistance, and improve outcomes for patients with cutaneous T-cell lymphoma.

DOI PubMed

医師と薬剤師との連携によるTDMを用いたCMLの外来治療【JST機械翻訳】|||

ABUMIYA Maiko, TAKAHASHI Naoto, MIURA Masatomo

日本血液学会学術集会抄録(Web)   87th   2025年

J-GLOBAL

慢性骨髄性白血病患者におけるアシミニブの薬物動態【JST機械翻訳】|||

TAKAHASHI Naoto, MIURA Masatomo

日本血液学会学術集会抄録(Web)   87th   2025年

J-GLOBAL

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年10月

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年10月

Protocol for a phase 2 study of bosutinib for amyotrophic lateral sclerosis using real-world data: Induced pluripotent stem cell-based drug repurposing for amyotrophic lateral sclerosis medicine (iDReAM) study

Imamura K.

BMJ Open ( BMJ Open )  14 ( 10 )   2024年10月

DOI

膜性腎症を合併し多彩な自己抗体陽性を認めた全身性強皮症

橋本 眞子, 阿部 史人, 齋藤 綾乃, 坂口 舞, 金澤 達郎, 齋藤 雅也, 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 )  34回   84 - 84   2024年10月

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年10月

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年10月

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年10月

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年10月

Asciminib in Patients With CML-CP Previously Treated With ≥ 2 Tyrosine Kinase Inhibitors: 96-Week Results From the Japanese Subgroup Analysis of the ASCEMBL Study

Minami Y.

International Journal of Hematology ( International Journal of Hematology )  120 ( 3 ) 305 - 313   2024年09月

Asciminib is a first-in-class BCR::ABL1 inhibitor that Specifically Targets the ABL1 Myristoyl Pocket (STAMP). It is approved worldwide and in Japan for chronic myeloid leukemia in chronic phase (CML-CP) with resistance or intolerance to previous tyrosine kinase inhibitor (TKI) therapy. In the Phase 3 ASCEMBL study, patients with CML-CP who received ≥ 2 prior ATP-competitive TKIs were randomized (2:1) to asciminib 40 mg twice-daily or bosutinib 500 mg once-daily. Here, we report the 96-week results of the subgroup analysis of Japanese patients (asciminib, n = 13; bosutinib, n = 3) in the ASCEMBL study. The MMR rate at Week 96 was 46.2% in asciminib-treated patients, increasing from Weeks 24 and 48. Patients who achieved MMR at Week 24 remained in MMR up to the Week 96 cutoff. While a high proportion of patients treated with asciminib remained on treatment at cutoff, none randomized to bosutinib were on treatment at Week 96. Despite the longer duration of exposure to asciminib, its safety and tolerability continued to be favorable with no new or worsening safety findings. Overall, the efficacy and safety outcomes in the Japanese subgroup were comparable with the ASCEMBL global study population, which supports the use of asciminib in Japanese patients with previously treated CML-CP.

DOI PubMed

ネフローゼ症候群を呈する巣状分節性糸球体硬化症を併発した糖原病Ia型の一例

坂口 舞, 齋藤 雅也, 橋本 眞子, 齋藤 綾乃, 阿部 史人, 野口 篤子, 金澤 達郎, 熊谷 拓哉, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  66 ( 6-E ) 953 - 953   2024年09月

7）慢性骨髄性白血病の治療の進歩

髙橋 直人

日本内科学会雑誌 ( 一般社団法人 日本内科学会 )  113 ( 9 ) 1732 - 1737   2024年09月

DOI CiNii Research

Real-world outcomes of ponatinib treatment in 724 patients with CML and Ph⁺ ALL: a post-marketing surveillance study with a special interest in arterial occlusive events in Japan

Takahashi N.

Japanese Journal of Clinical Oncology ( Japanese Journal of Clinical Oncology )  54 ( 8 ) 930 - 938   2024年08月

DOI

保存期CKDにおける赤血球分布幅とESA初期治療抵抗性の関連

金澤 達郎, 齋藤 雅也, 齋藤 綾乃, 阿部 史人, 橋本 眞子, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  66 ( 4 ) 630 - 630   2024年06月

糖尿病性腎病腎組織におけるToll-like receptor 4発現と腎予後の検討

齋藤 綾乃, 阿部 史人, 齋藤 雅也, 金澤 達郎, 橋本 眞子, 坂口 舞, 中山 隆弘, 大谷 浩, 澤村 昌人, 奥山 慎, 政井 理恵, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  66 ( 4 ) 673 - 673   2024年06月

Development and evaluation of a rapid one-step high sensitivity real-time quantitative PCR system for minor BCR-ABL (e1a2) test in Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)

Hidaka M.

Japanese Journal of Clinical Oncology ( Japanese Journal of Clinical Oncology )  54 ( 2 ) 153 - 159   2024年02月

OBJECTIVE: Minimal residual disease assessment of BCR-ABL messenger ribonucleic acid levels is crucial in Philadelphia chromosome-positive acute lymphoblastic leukemia for prognosis and treatment planning. However, accurately quantifying minor BCR-ABL transcripts, which comprise 70% of Philadelphia chromosome-positive acute lymphoblastic leukemia cases, lacks a national-approved method. METHODS: We developed the "Otsuka" minor BCR-ABLmessenger ribonucleic acid assay kit with exceptional precision (0.00151%). Minor BCR-ABL messenger ribonucleic acid levels were analyzed in 175 adults, 36 children with acute lymphoblastic leukemia and 25 healthy individuals to evaluate the kit's performance. RESULTS: The "Otsuka" kit showed high concordance with a commonly used chimeric gene screening method, indicating reliable detection of positive cases. Quantitative results demonstrated a robust correlation with both a laboratory-developed test and a diagnostic research product. The "Otsuka" kit performs comparably or even surpass to conventional products, providing valuable insights into Philadelphia chromosome-positive acute lymphoblastic leukemia pathology. CONCLUSIONS: The 'Otsuka" minor BCR-ABL messenger ribonucleic acid assay kit exhibits excellent performance in quantifying minor BCR-ABL transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia patients. Our results align well with established screening methods and show a strong correlation with laboratory-developed tests and diagnostic research products. The "Otsuka" kit holds great promise as a valuable tool for understanding Philadelphia chromosome-positive acute lymphoblastic leukemia pathology and guiding effective treatment strategies.

DOI PubMed

7．慢性骨髄性白血病の治療の進歩

髙橋 直人

日本内科学会雑誌 ( 一般社団法人 日本内科学会 )  113 ( Suppl ) 120a - 120a   2024年02月

DOI CiNii Research

Prognostic impact of peripheral blood WT1 mRNA dynamics in patients with acute myeloid leukemia treated with venetoclax combination therapy

Sato H.

International Journal of Clinical Oncology ( International Journal of Clinical Oncology )  29 ( 4 ) 481 - 492   2024年

DOI

クローン病の治療中に発症し臍帯血移植が奏効した化学療法抵抗性<i>γδ</i>型肝脾T細胞リンパ腫

齊藤 暉人, 奈良 美保, 藤島 崇嗣, 黒木 航, 山下 鷹也, 小林 敬宏, 池田 翔, 北舘 明宏, 亀岡 吉弘, 高橋 直人

臨床血液 ( 一般社団法人 日本血液学会 )  65 ( 1 ) 41 - 46   2024年

<p>症例21歳男性。Crohn病のためinfliximab，azathioprineによる治療を受けていたが6年後，発熱，LDH 2,473 U/<i>l</i>，血小板低下，肝脾腫を認めた。骨髄生検と肝生検でCD4，CD56，TCR<i>γδ</i>陽性，CD8陰性の異型細胞を認め，肝脾T細胞リンパ腫（hepatosplenic T-cell lymphoma, HSTCL）と診断した。CHOP療法，dose-adjusted-EPOCH療法後に非寛解状態で骨髄破壊的前処置による臍帯血移植を行った。退院前造影CTで肝脾腫縮小，LDH 165 U/<i>l</i>，血小板18万/µ<i>l</i>と正常化を認めday117に退院した。HSTCLは脾臓内のV<i>δ</i>1遺伝子変異を伴う未熟な<i>γδ</i>T細胞をカウンターパートとする腫瘍であり，発症には免疫不全状態の関与が示唆されており予後は不良である。Azathioprineで治療された炎症性腸疾患患者はリンパ増殖性疾患リスクが増加することが知られており，本症例もCrohn病に対する免疫抑制剤の使用により腸管上皮に存在する<i>γδ</i>細胞が悪性化した可能性がある。化学療法抵抗性であったが早期の臍帯血移植で寛解を達成し，長期予後を期待している。</p>

DOI PubMed CiNii Research

A practice-oriented genome-profiling study for acute myeloid leukemia using the novel HANDLE system: HM-screen-JAPAN02

Arai H.

International Journal of Hematology ( International Journal of Hematology )  121 ( 3 ) 378 - 387   2024年

DOI

JSH practical guidelines for hematological malignancies, 2023: leukemia-4. Chronic myeloid leukemia (CML)/myeloproliferative neoplasms (MPN)

Takahashi N.

International Journal of Hematology ( International Journal of Hematology )  121 ( 1 ) 5 - 38   2024年

DOI

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年

CiNii Research

Case report: Three characteristics of tyrosine kinase inhibitor-associated cerebrovascular stenosis. High threshold for infarction, atypical infarct area, and vascular recoverability under the use of ponatinib

Hanazono A.

Frontiers in Stroke ( Frontiers in Stroke )  3   2024年

DOI

チロシンキナーゼ阻害剤の薬物血中濃度モニタリングを施行した小児白血病

田村真一, 飛鳥暉晶, 内藤優樹, 友安千紘, 矢野未央, 石田宏之, 岡野創造, 三浦昌朋, 高橋直人, 黒田啓史

近畿小児科学会プログラム・抄録集   37th   2024年

J-GLOBAL

Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial

Cortes J.E.

Future Oncology ( Future Oncology )  18 ( 38 ) 4161 - 4170   2023年12月

DOI

経口薬で白血病を治す－CMLに対する分子標的療法の挑戦

高橋 直人

日本医療薬学会年会講演要旨集 ( 一般社団法人 日本医療薬学会 )  33 ( 0 ) 4 - 4   2023年11月

DOI 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年10月

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年10月

Clinical Course of a Rare Epstein-Barr Virus-Associated Smooth Muscle Tumor and Its Genomic Analysis

Miyahara J.

Case Reports in Oncology ( Case Reports in Oncology )  16 ( 1 ) 577 - 584   2023年08月

Epstein-Barr virus (EBV) can rarely induce smooth muscle tumors (SMTs). A 20-year-old female patient underwent kidney transplantation for renal failure. Since then, she has been treated with immunosuppressants, including a calcineurin inhibitor, tacrolimus, and prednisolone, owing to the immunological rejection. Three years later, she developed large liver tumors (diameter >5 cm) and multiple small lung tumors that were identified as EBV-SMTs based on the results of liver biopsy/histopathology. No intervention was performed except for the addition of a mammalian target of the rapamycin inhibitor, everolimus, which inhibits both immune reaction and SMT growth. Finally, after 8 years, the transplanted kidney became nonfunctional, and immunosuppressant administration became unnecessary as urinary dialysis was started. Under these circumstances, SMT growth was observed despite the absence of immunosuppressant administration. Three months after the cessation of the immunosuppressants, EBV-SMTs in the liver and lungs shrank slightly. To the best of our knowledge, this is the first report on the genomic profile of this rare tumor. The clinical course of our patient indicates that EBV can induce SMTs, and immunological suppression of EBV may inhibit the activity of these tumors.

DOI PubMed

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年07月

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

保存期CKDにおけるESA初期治療抵抗性と予後に関する検討

金澤 達郎, 齋藤 雅也, 齋藤 綾乃, 阿部 史人, 加賀 一, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  65 ( 3 ) 294 - 294   2023年05月

糖尿病性腎臓病腎組織におけるToll-like receptor 4発現と病理学的検討

齋藤 綾乃, 阿部 史人, 齋藤 雅也, 加賀 一, 金澤 達郎, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  65 ( 3 ) 317 - 317   2023年05月

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年05月

Outcomes of adult patients with early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) and non-ETP T-ALL

Onishi Y.

International Journal of Hematology ( International Journal of Hematology )  117 ( 5 ) 738 - 747   2023年

DOI

Clinical utility of genomic profiling of AML using paraffin-embedded bone marrow clots: HM-SCREEN-Japan 01

Hosono N.

Cancer Science ( Cancer Science )  114 ( 5 ) 2098 - 2108   2023年

DOI

難治性食道狭窄を来した同種造血幹細胞移植後の食道粘膜類天疱瘡

藤田 菜々子, 山下 鷹也, 阿部 史人, 奈良 美保, 吉岡 智子, 古賀 浩嗣, 石井 文人, 高橋 直人

臨床血液 ( 一般社団法人 日本血液学会 )  64 ( 2 ) 107 - 112   2023年

<p>40代女性。AML再発に対し血縁者間HLA半合致移植を施行。移植後day59に食道狭窄症を発症した。GVHDと診断し免疫抑制療法中は定期的な食道拡張術で安定していたが，AML再々発に伴い免疫抑制剤を中止すると食道狭窄の増悪を認めた。食道粘膜は易出血性・易剥離性であり，生検組織で剥脱した重層扁平上皮と上皮下の肉芽組織との離開を認めた。蛍光抗体直接法で基底膜部へのIgGとIgAの線状沈着を認め，蛍光抗体間接法ではIgG陰性，IgAが表皮側で陽性，BP180のC末端部位リコンビナント蛋白を用いた免疫ブロット法ではIgG，IgAが陽性であり，抗BP180型粘膜類天疱瘡と診断した。同種移植後の類天疱瘡はGVHDにより表皮の基底細胞が傷害され基底膜部蛋白が露出し，抗原提示されることにより生じると考えられている。本症例も同様の機序と考えられ，典型的なGVHDと異なる症例では詳細な組織診断が重要である。</p>

DOI CiNii Research

c-FOS転写因子はIKZF1標的遺伝子の転写活性化を介して免疫調節薬耐性を誘導する

長田直希, 菊池次郎, 松岡紗恵, 安井寛, 池田翔, 高橋直人, 仲宗根秀樹, 古川雄祐

日本癌学会学術総会抄録集(Web)   82nd   2023年

J-GLOBAL

Bosutinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia: final 3-year follow-up results of a phase 2 study

Ono T.

International Journal of Hematology ( International Journal of Hematology )  116 ( 6 ) 871 - 882   2022年12月

Bosutinib has been evaluated for treatment of chronic-phase chronic myeloid leukemia (CP-CML) in several clinical studies, including in Japan. This open-label, single-arm, phase 2 study evaluated the efficacy and safety of bosutinib at a starting dose of 400 mg once daily in Japanese patients (n = 60) with newly diagnosed CP-CML. The minimum follow-up period was 3 years and median duration of treatment was 35.9 months. At study completion, 60% of patients were still on treatment. Cumulative rates of major molecular response (MMR), molecular response4 (MR4), and MR4.5 at any time were 70.0%, 53.3%, and 48.3%, respectively. No patient who achieved MMR or MR4 had a confirmed loss of response. No patient experienced on-treatment transformation to accelerated/blast phase or died within 28 days of the last bosutinib dose. Any-grade treatment-emergent adverse events (TEAEs) occurred in 100% (grade ≥ 3: 81.7%) of patients. The most common TEAEs were diarrhea (86.7%), increased alanine aminotransferase (55.0%), and increased aspartate aminotransferase (46.7%). No new safety signals emerged during the follow-up period. Bosutinib continues to demonstrate a favorable benefit/risk profile and is an important treatment option for Japanese patients with newly diagnosed CP-CML. Optimal management of TEAEs during initial treatment with bosutinib should be prioritized.Trial Registration: ClinicalTrials.gov ID: NCT03128411.

DOI PubMed

Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy

Kaga H.

Clinical Proteomics ( Clinical Proteomics )  19 ( 1 )   2022年12月

DOI

Evaluation of protein production in rice seedlings under dark conditions

Watanabe A.

Scientific Reports ( Scientific Reports )  12 ( 1 )   2022年12月

DOI

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

Imamura K.

eClinicalMedicine ( eClinicalMedicine )  53   2022年11月

DOI

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

今村 恵子, 和泉 唯信, 永井 真貴子, 西山 和利, 渡辺 保裕, 花島 律子, 江川 斉宏, 綾木 孝, 沖 良祐, 藤田 浩司, 魚住 龍史, 森永 明子, 廣橋 朋子, 藤井 陽介, 山本 拓也, 建部 陽嗣, 徳田 隆彦, 高橋 直人, 森田 智視, 髙橋 良輔, 井上 治久

eClinicalMedicine ( Elsevier BV )  53   2022年11月

[Background] Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. [Methods] An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1–3 points during the 12-week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. [Findings] Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg–400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. [Interpretation] This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required.

CiNii Research

High baseline total lesion glycolysis predicts early progression of disease within 24 months in patients with high-tumor-burden follicular lymphoma

Kuroki W.

International Journal of Hematology ( International Journal of Hematology )  116 ( 5 ) 712 - 722   2022年11月

Despite the introduction of rituximab-containing regimens, approximately 20% of patients with follicular lymphoma (FL) still experience progression of disease within 24 months (POD24) and have poor overall survival. Therefore, a more accurate risk assessment tool is required. We investigated the predictive value of two new volume-based parameters determined from baseline 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), baseline total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), in 45 patients with high-tumor-burden FL who underwent baseline PET/CT. We observed that high TMTV, high TLG, and poor initial treatment response (less than complete [metabolic] response [non-CR/CMR] at the end of induction therapy) independently predicted poor PFS. Notably, POD24-positive patients were more common in the high-TLG group than in the high-TMTV group, which suggests that TLG is a stronger predictor of outcomes than TMTV. Combining baseline TLG and initial treatment response showed that patients with both high TLG and non-CR/CMR experienced significantly poorer outcomes, with a 2 year PFS of 0% (hazard ratio 60.39, P = 0.000002). This combination had 56% sensitivity and 100% specificity for detecting patients who would experience POD24. Baseline TLG and initial treatment response can precisely identify patients at high risk of POD24.

DOI PubMed

膜性腎症・V型ループス腎炎におけるExostosin1/Exostosin2の検討

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

秋田腎不全研究会誌 ( 秋田腎不全研究会 )  25   33 - 37   2022年11月

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

膜性腎症・V型ループス腎炎におけるExostosin1/Exostosin2の検討

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

秋田腎不全研究会誌 ( 秋田腎不全研究会 )  25   33 - 37   2022年11月

当院と関連施設で1990～2020年に腎生検を施行された症例のうち、膜性腎症と診断された374例と、V型ループス腎炎と診断された66例を対象とし、Exostosin(EXT)1/2の検出率について調査した。結果、膜性腎症患者のうちPLA2R陽性例(98例)でEXT1/2が検出されたものは1例もなく、PLA2R陰性例(174例)ではEXT1/2が4例(2%)で検出された。ループス腎炎患者では19例(29%)でEXT1/2が検出された。ループス腎炎患者をEXT1/2陽性群と陰性群に分け、ネフローゼ症候群の合併率、細胞増殖性病変の合併率、腎障害の程度、抗ds-DNA抗体陽性率、低補体血症の合併率などについて群間比較した結果、いずれも有意差は認められなかった。

Quantitation of Venetoclax in Human Plasma by High-Performance Liquid Chromatography with Ultraviolet Detection

Natsuki Fukuda, Takahiro Kobayashi, Honami Sato, Yumiko Akamine, Naoto Takahashi, Masatomo Miura

Journal of Chromatographic Science ( Oxford University Press (OUP) )  62 ( 1 ) 58 - 64   2022年10月

Abstract

A simple, highly sensitive and specific method based on high-performance liquid chromatography (HPLC) with ultraviolet detection was developed for the measurement of venetoclax concentrations in plasma samples. The chromatographic method employed a mobile phase of acetonitrile: 0.5% KH2PO4 (pH 3.5) (80/20, v/v) on a CAPCELL PAK C18 UG120 column at a flow rate of 0.5 mL/min. The quantitative method was validated based on standards described in “Bioanalytical Method Validation: Guidance for Industry” published by the US Food and Drug Administration. The separation of venetoclax and the internal standard R051012 was satisfactory, and the chromatograms were free of interfering peaks from the biological matrix. The intra- and inter-day coefficients of variation for venetoclax assays were &amp;lt;12.9%, whereas intra- and inter-day accuracies were within 13.6%. Only 100 μL of human plasma was required to detect a lower limit of quantification of 10 ng/mL for venetoclax. The recoveries of venetoclax extracted with an Oasis HLB cartridge were between 81 and 85%. The developed HPLC method was successfully applied to the determination of venetoclax concentrations in plasma of acute myeloid leukemia patients taking venetoclax. The degree of drug interactions between venetoclax and CYP3A4 inhibitors can be determined by this HPLC assay.

DOI

コロナワクチン2回目接種直後にIgA血管炎を発症した一例

和田 邦宏, 澤村 昌人, 橋本 眞子, 阿部 史人, 加賀 一, 斉藤 綾乃, 斉藤 雅也, 小松田 敦, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  64 ( 6-E ) 545 - 545   2022年10月

CML-423 Trial in Progress: A Phase III Study of Asciminib vs an Investigator-Selected Tyrosine Kinase Inhibitor (TKI) in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

Hughes T.P.

Clinical Lymphoma, Myeloma and Leukemia ( Clinical Lymphoma, Myeloma and Leukemia )  22   S297 - S298   2022年10月

DOI

秋田県腎生検症例におけるExostosin1/Exostosin2の検討

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

日本臨床免疫学会総会プログラム・抄録集 ( (一社)日本臨床免疫学会 )  50回   103 - 103   2022年10月

Long-term prognosis of monoclonal immunoglobulin-associated glomerular diseases with non-organized deposits: A report of 38 cases from a Japanese single center

Nara M.

Clinical Nephrology ( Clinical Nephrology )  98 ( 3 ) 135 - 146   2022年09月

Monoclonal immunoglobulin (MIg)-associated glomerular diseases with non-organized deposits are rare disorders. They have recently been categorized into light chain deposit disease (LCDD), light and heavy chain deposit disease (LHCDD), heavy chain deposit disease (HCDD), proliferative glomerulonephritis with MIg deposits (PGNMID) and its light chain only variant (PGNMID-LC), and membranous glomerulopathy with light chain-restricted deposits (MG-LC). In our Japanese cohort of more than 9,500 patients who underwent renal biopsy (1979 - 2020), we evaluated clinicopathological features and long-term outcomes in 38 patients with MIg-associated glomerular diseases with non-organized deposits: LCDD (n = 9), LHCDD (n = 8), HCDD (n = 5), PGNMID-membranoproliferative glomerulonephritis (MPGN) (n = 7), PGNMID-LC (n = 2), and MG-LC (n = 7). In patients with LCDD, a low estimated glomerular filtration rate (eGFR) at biopsy, a high detection rate of urinary MIgs, a high incidence rate of multiple myeloma, and sever tubulointerstitial and vascular lesions were significant clinicopathological characteristics. Median duration of follow-up in each group was 42 - 114 months. Most patients were treated with steroid-based therapy. Patients with LCDD, LHCDD, HCDD, and MG-LC were recently treated with bortezomib-based therapy. Renal survival rate was significantly shorter for LCDD than of PGNMID and MG-LC. Patient survival rate was significantly longer for MG-LC than HCDD and PGNMID. Major causes of death were pulmonary and cardiovascular complications. Among disease groups, significant differences were observed in eGFR at biopsy, detection rates of urinary MIgs, incidence rates of multiple myeloma, severities of tubulointerstitial and vascular lesions, and long-term outcomes.

DOI PubMed

Safe administration and pharmacokinetic monitoring of crushed venetoclax tablets with posaconazole and clarithromycin via percutaneous endoscopic gastrostomy tube in a patient with acute myeloid leukemia

Sato H.

Cancer Chemotherapy and Pharmacology ( Cancer Chemotherapy and Pharmacology )  90 ( 3 ) 279 - 284   2022年09月

PURPOSE: Leukemic stem cells in acute myeloid leukemia (AML) express high B cell lymphoma 2 (BCL2) levels, which contribute to leukemic cell survival and resistance to therapy. Venetoclax-a BCL-2 inhibitor-is indicated for the treatment of AML, which may also target leukemic stem cells; however, it is only available as a tablet. There are no reports of venetoclax use in patients who cannot take oral drugs; therefore, the efficacy, safety, and pharmacokinetics (PK) of venetoclax administered through a gastrostomy tube is unknown. CASE PRESENTATION: We report, for the first time, a case of relapsed Japanese AML patient treated with crushed venetoclax tablets through a percutaneous endoscopic gastrostomy (PEG) tube because of esophageal stricture due to complications of stem cell transplantation. The patient was also taking posaconazole and clarithromycin concomitantly. We evaluated the plasma concentrations of venetoclax administered through a PEG tube. Time to maximum concentration, maximum plasma concentration, and the area under the plasma concentration-time curve were similar to the previously reported PK parameters after oral administration of intact venetoclax tablets in Japanese patients with AML. The clinical course passed safely without the occurrence of unexpected adverse events during the administration of crushed venetoclax tablets in combination with azacitidine. CONCLUSIONS: The PK parameters of the crushed administered venetoclax via PEG tube was similar to the previously reported PK parameters of the orally administered venetoclax. Therefore, administration of crushed venetoclax tablets through a PEG tube could be an alternate route for patients who have difficulty with oral administration.

DOI PubMed

EMD originates from hyaluronan-induced homophilic interactions of CD44 variant-expressing MM cells under shear stress

Jiro Kikuchi, Nobuyuki Kodama, Masataka Takeshita, Sho Ikeda, Takahiro Kobayashi, Yoshiaki Kuroda, Michihiro Uchiyama, Naoki Osada, Bjarne Bogen, Hiroshi Yasui, Naoto Takahashi, Akiyoshi Miwa, Yusuke Furukawa

Blood Advances ( American Society of Hematology )  7 ( 4 ) 508 - 524   2022年08月

Extramedullary disease (EMD) is known to be associated with chemoresistance and poor prognosis in multiple myeloma (MM); however, the mechanisms of its development are not fully understood. Elucidating the mechanism of EMD development and its therapeutic targeting would greatly contribute to further improvement of treatment outcome in MM patients. Here, we show that bone marrow stroma cell-derived hyaluronan elicits homophilic interactions of MM cells by binding to surface CD44, especially long-stretch variants, under physiological shear stress and generates cell clusters that might develop into EMD. We recapitulated the development of EMD via administration of hyaluronan in a syngeneic murine MM model in a CD44-dependent manner. Hyaluronan-induced MM cell clusters exhibited the specific resistance to proteasome inhibitors (PIs) in vitro and in murine models via γ-secretase-mediated cleavage of the intracellular domains of CD44, which in turn transactivated PI resistance-inducible genes. Treatment of hyaluronan-injected mice with anti-CD44 antibody or γ-secretase inhibitors readily suppressed the development of EMD from transplanted MM cells and significantly prolonged the survival of recipients by overcoming PI resistance. The hyaluronan-CD44 axis represents a novel pathway to trigger EMD development and could be a target of the prediction, prevention, and treatment of EMD in MM patients.

DOI

Evaluation of a newly proposed renal risk score for Japanese patients with ANCA-associated glomerulonephritis

Saito M.

Clinical and Experimental Nephrology ( Clinical and Experimental Nephrology )  26 ( 8 ) 760 - 769   2022年08月

BACKGROUND: We determined the usefulness and prognostic ability of the renal risk score (RRS), proposed in Europe, for Japanese patients with antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) and high myeloperoxidase (MPO)-ANCA positivity; these aspects remain to be verified. METHODS: This retrospective study was conducted on 86 Japanese patients with new, biopsy-confirmed AAGN. We calculated the RRS and analyzed the relationship between this classification, and clinicopathological features and prognosis. We also compared the predictive values between RRS for endpoints including renal death and conventional prognostic tools for patients with AAGN. RESULTS: There were 33, 37, and 16 patients in the low-, medium-, and high-risk groups, respectively. All patients were MPO-ANCA positive. The median follow-up period was 33 months; 16 (18.6%) patients progressed to end-stage renal disease (ESRD). In the high-risk group, 9/16 (56.3%) patients progressed to ESRD, and renal prognosis was significantly poorer than that in other groups (low-risk group, P < 0.001; medium-risk group, P = 0.004). In Cox multivariate regression analysis, RRS was an independent, poor renal prognostic factor (hazard ratio 5.22; 95% confidence interval 2.20-12.40; P < 0.001). The receiver-operating characteristic curves of the RRS for each endpoint were comparable with those of the 2010 histological classification and those of the severity classification of Japanese rapidly progressive glomerulonephritis. CONCLUSIONS: This is the first study to report the usefulness of the RRS for predicting renal outcomes among Japanese patients with AAGN. Our predictive value of the RRS was comparable with that of conventional prognostic tools.

DOI PubMed

Refractory IgG4-related disease complicated with organising pneumonia and hypertrophic pachymeningitis

Abe F.

Modern Rheumatology Case Reports ( Modern Rheumatology Case Reports )  6 ( 2 ) 278 - 281   2022年06月

IgG4-related disease (IgG4-RD) involves multiple organs, including the lungs and central nervous system. Lung lesions are frequently reported as mass lesions or non-specific interstitial pneumonia, whereas organizing pneumonia (OP) due to IgG4-RD is rare. Furthermore, limited information is currently available on hypertrophic pachymeningitis (HP). We herein report a case of IgG4-RD complicated with OP and HP. The diagnosis was confirmed based on the serum concentration of IgG4 and the results of salivary gland and transbronchial lung biopsies. HP did not respond to steroid monotherapy and was also resistant to rituximab and intravenous cyclophosphamide; however, the combination therapy of methotrexate and dexamethasone was effective.

DOI PubMed

脾臓浸潤による非外傷性脾破裂をきたし剖検で確定診断した血管内大細胞型B細胞リンパ腫

黒木 航, 小林 敬宏, 馬越 通信, 北舘 明宏, 今泉 ちひろ, 齋藤 雅也, 小林 五十鈴, 藤島 眞澄, 藤島 直仁, 吉岡 智子, 後藤 明輝, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  63 ( 6 ) 523 - 529   2022年06月

非外傷性脾破裂(ASR)は悪性リンパ腫の致死的合併症である。血管内大細胞型B細胞リンパ腫(IVLBCL)に伴うASR(IVLBCL-ASR)の報告は過去に1例のみで,その機序は不明な点が多い。今回我々は,剖検所見からIVLBCL-ASRと診断した1例を報告する。症例は78歳男性。IVLBCLの精査中に出血性ショックのため突然死し,剖検所見で大量の血性腹水と脾破裂を認めた。全身の小血管内にCD20陽性大型異型リンパ球の浸潤を認めIVLBCLと診断し,腫瘍細胞浸潤は裂創部位を含めた脾被膜部ではわずかで脾臓中心部で著明で,脾中心部での腫瘍増殖による脾内圧亢進がASRの原因と考えられIVLBCL-ASRと確定診断した。患者は入院3ヵ月前に舌がんの精査目的で施行された18F-FDGPET/CT検査で右副腎に異常集積を認めており,病理所見では同部位に一致して腫瘍浸潤を認めた。IVLBCLの早期診断における18F-FDG PET/CT検査の有用性を再認識し,IVLBCLの進行に伴いASRの発症リスクが上昇することが示唆され,早期の全身化学療法の実施が重要であると考えられた。(著者抄録)

Relationship between achievement of major molecular response or deep molecular response and nilotinib plasma concentration in patients with chronic myeloid leukemia receiving first-line nilotinib therapy

Fukuda N.

Cancer Chemotherapy and Pharmacology ( Cancer Chemotherapy and Pharmacology )  89 ( 5 ) 609 - 616   2022年05月

DOI

ネフローゼ症候群に対するリツキシマブ維持療法の有効性と安全性の検討

加賀 一, 橋本 眞子, 阿部 史人, 齋藤 綾乃, 齋藤 雅也, 奈良 瑞穂, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  64 ( 3 ) 266 - 266   2022年05月

同種造血幹細胞移植後に粘膜類天疱瘡による難治性食道狭窄症を来した1例

藤田 菜々子, 山下 鷹也, 阿部 史人, 斎藤 綾乃, 北舘 明宏, 奈良 美保, 吉岡 智子, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  63 ( 5 ) 490 - 490   2022年05月

薬物モニタリングにより胃瘻からのベネトクラクス粉砕投与が安全に施行できた再発急性骨髄性白血病

佐藤 保奈実, 小林 敬宏, 藤田 菜々子, 吉岡 智子, 奈良 美保, 三浦 昌朋, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  63 ( 5 ) 489 - 489   2022年05月

Successful rituximab treatment of an elderly Japanese patient with HHV8-positive, HIV-negative multicentric Castleman disease

Kaga H.

International Journal of Hematology ( International Journal of Hematology )  115 ( 1 ) 129 - 134   2022年01月

Human herpesvirus-8 (HHV8)-positive, human immunodeficiency virus (HIV)-negative multicentric Castleman disease (MCD) is a rare and age-related lymphoproliferative disorder caused by cytokine storm. Rituximab treatment is currently recommended because B-cell depletion eliminates the primary reservoir for HHV8. We report the first case of effective rituximab treatment of a Japanese patient (an 87-year-old woman) with this disorder. Her inflammatory symptoms and lymphadenopathy improved after medium-dose steroid therapy, but these symptoms recurred during steroid tapering. After one course of rituximab therapy, she achieved sustained remission. HHV8-associated MCD should be considered as a possible diagnosis in HIV-negative patients with inflammatory symptoms and lymphadenopathy.

DOI

Downregulation of miR-26 promotes invasion and metastasis via targeting interleukin-22 in cutaneous T-cell lymphoma

Matsuda Y.

Cancer Science ( Cancer Science )    2022年

DOI

Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia: a pooled analysis

Takahashi N.

International Journal of Hematology ( International Journal of Hematology )    2022年

DOI

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

Wataru Kuroki, Takahiro Kobayashi, Michinobu Umakoshi, Akihiro Kitadate, Chihiro Imaizumi, Masaya Saito, Isuzu Kobayashi, Masumi Fujishima, Naohito Fujishima, Tomoko Yoshioka, Akiteru Goto, Naoto Takahashi

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 一般社団法人 日本血液学会 )  63 ( 6 ) 523 - 529   2022年

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.

DOI PubMed CiNii Research

Adult-onset Still's Disease during Pregnancy Treated with Tocilizumab

Imaizumi C.

Internal Medicine ( Internal Medicine )  61 ( 20 ) 3137 - 3140   2022年

A 28-year-old woman exhibited a spiking fever, arthritis, and liver disfunction when she was 22 weeks pregnant. She was diagnosed with adult-onset Still's disease (AOSD). As her condition was resistant to corticosteroid therapy, tocilizumab (TCZ) was selected. The TCZ treatment was effective, and she delivered a healthy child while receiving TCZ treatment. Cases in which AOSD first arises during pregnancy are rare, and there have been no reports of TCZ treatment for AOSD being initiated during pregnancy. Although the safety of TCZ treatment during pregnancy has not been established, it may be effective against severe AOSD that develops during pregnancy.

DOI PubMed CiNii Research

Asciminib vs bosutinib in CML patients pretreated with ≥2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study

Yuda J.

Cancer Medicine ( Cancer Medicine )  12 ( 3 ) 2990 - 2998   2022年

Asciminib, a first-in-class, allosteric inhibitor of BCR-ABL1 that acts by STAMP (Specifically Targeting the ABL Myristoyl Pocket), is a novel therapeutic option for patients with chronic myeloid leukemia (CML). In the global, phase 3, open-label ASCEMBL study in patients with CML in chronic phase (CML-CP) pretreated with ≥2 tyrosine kinase inhibitors (TKIs) (NCT03106779), asciminib (40 mg twice-daily) demonstrated significant superiority over the ATP-competitive TKI bosutinib (500 mg once daily) for the primary endpoint of major molecular response (MMR; BCR::ABL1 transcript levels on the international scale [BCR::ABL1IS ] ≤0.1%) at week 24. Here, we report results from a descriptive subgroup analysis of Japanese patients enrolled in ASCEMBL study (data cut-off: May 25, 2020). Overall, 16 Japanese patients were randomized (asciminib, n = 13; bosutinib, n = 3). At week 24, the MMR rate with asciminib was 30.8% (4/13; 95% confidence interval [CI], 9.09-61.43). BCR::ABL1IS ≤1% and complete cytogenic response (CCyR) at week 24 were 61.5% (8/13 patients) and 50.0% (4/8 patients), respectively. In the bosutinib group, no patient achieved MMR, CCyR, or BCR::ABL1IS ≤1%, but results were limited by the low number of patients. The safety profile of asciminib was comparable to that previously observed in the overall study population. Findings from this Japanese subgroup analysis of the ASCEMBL study support the use of asciminib for the treatment of Japanese patients with CML-CP previously treated with ≥2 TKIs. ClinicalTrials.gov Identifier: NCT03106779.

DOI PubMed

Bortezomib-EPOCH併用療法により長期寛解が得られたHIV陰性精巣原発形質芽球性リンパ腫

藤島 崇嗣, 川端 良成, 道下 吉広, 北林 淳, 高橋 直人

臨床血液 ( 一般社団法人 日本血液学会 )  63 ( 10 ) 1386 - 1391   2022年

<p>形質芽球性リンパ腫（PBL）は，HIV感染や免疫不全を背景に発症する稀なB細胞性リンパ腫である。今回，我々はHIV陰性精巣原発PBLに対し，bortezomib併用-EPOCH療法が著効し長期寛解が得られた症例を経験したので報告する。症例は86歳男性。免疫不全を伴う基礎疾患なし。急速に増大する右精巣腫瘍を認め，右高位精巣摘除術を施行した。摘除標本で形質細胞様異型リンパ球のびまん性増殖を認め，免疫組織化学染色で，CD38，CD138，CD56，λ，MUM1，EBER，MYC陽性であるが，CD20陰性，MIB1 index 90％であった。PET/CTで全身リンパ節腫脹を認めたが，骨髄および髄液浸潤はなく，PBL，臨床病期IIIE-A，IPI高中間リスクと診断した。髄注併用V-EPOCH療法を6コース施行し完全寛解が得られた。左精巣に予防的照射（計30 Gy）施行後，診断から2年半以上経過したが完全寛解を維持している。PBLは急速進行性で予後不良な疾患であるが，その稀少性から標準的治療は未確立である。精巣原発PBLに対し，髄注および局所照射を併用したV-EPOCH療法は，高齢者にも寛解と長期予後を期待できる有効な初期治療法の一つと考えられた。</p>

DOI PubMed CiNii Research

Deep molecular response in patients with chronic phase chronic myeloid leukemia treated with the plasminogen activator inhibitor-1 inhibitor TM5614 combined with a tyrosine kinase inhibitor

Takahashi N.

Cancer Medicine ( Cancer Medicine )    2022年

DOI

Development of an automatic multiplanar reconstruction processing method for head computed tomography

Sato M.

Journal of X-Ray Science and Technology ( Journal of X-Ray Science and Technology )  30 ( 4 ) 777 - 788   2022年

DOI

Early Pulmonary Rehabilitation with Neuromuscular Electrical Stimulation in a Patient with Acute Exacerbation of Rheumatoid Arthritis-associated Interstitial Lung Disease: A Case Report

OKURA Kazuki, TAKAHASHI Yusuke, HASEGAWA Kakeru, HATAKEYAMA Kazutoshi, SAITO Kimio, IMAIZUMI Chihiro, KAGA Hajime, TAKAHASHI Naoto

Physical Therapy Research ( 一般社団法人日本理学療法学会連合 )  advpub ( 0 )   2022年

<p>Introduction: Early implementation of neuromuscular electrical stimulation (NMES) has been reported to prevent muscle atrophy and physical functional decline in patients requiring mechanical ventilation. However, its effect in patients with acute exacerbation of interstitial lung disease (ILD) remains unclear. We herein report our experience using the NMES combined with mobilization in a patient with an acute exacerbation of rheumatoid arthritis-associated ILD (RA-ILD) requiring mechanical ventilation. Case presentation: A 74-year-old man was admitted to the intensive care unit (ICU) and put on mechanical ventilation due to severe acute exacerbation of RA-ILD. Early mobilization and the NMES using a belt electrode skeletal muscle electrical stimulation system were started on day 7 of hospitalization (day 2 of ICU admission). The NMES duration was 20 min, performed once daily. The patient could perform mobility exercises on day 8 and could walk on day 16. We assessed his rectus femoris and quadriceps muscle thicknesses using ultrasound imaging, and found decreases of 4.5% and 8.4%, respectively, by day 14. On day 27, he could independently visit the lavatory, and the NMES was discontinued. He was instructed to start long-term oxygen therapy on day 49 and was discharged on day 63. His 6-minute walk distance was 308 m and his muscle thickness recovered to levels comparable to those at the initial evaluation at the time of discharge. Conclusion: Combining the NMES and mobilization started in the early phase and continued after ICU discharge was safe and effective in a patient with a severe acute exacerbation of RA-ILD.</p>

DOI CiNii Research

Improving performance and self-efficacy of novice nurses using hybrid simulation-based mastery learning

Takashiki R.

Japan Journal of Nursing Science ( Japan Journal of Nursing Science )    2022年

DOI

Ovarian Follicular Lymphoma Diagnosed due to Hydronephrosis

Noguchi Shinsuke, Kimura Yuiko, Shibano Sumire, Ariake Chika, Iwasawa Takuya, Oyama Noriaki, Sato Hirokazu, Enomoto Katsuhiko, Takahashi Naoto

Japanese Journal of Medicine ( 一般社団法人 日本内科学会 )  advpub ( 0 ) 293 - 298   2022年

<p>A 74-year-old woman presented with left lateral abdominal pain. Abdominal echography revealed left hydronephrosis and a pelvic mass. The patient underwent left adnexal resection of a suspected left ovarian tumor and was diagnosed with follicular lymphoma (FL) of clinical stage IIIA, grade 2. The patient was treated with rituximab-combined chemotherapy and achieved complete remission. The most common histological types of ovarian lymphoma are diffuse large B-cell lymphoma and Burkitt lymphoma, with FL being an extremely rare variant. We herein report a case of ovarian FL diagnosed as hydronephrosis. </p>

DOI PubMed CiNii Research

Clinical outcomes of second-generation tyrosine kinase inhibitors versus imatinib in older patients with CML

Ono T.

Cancer Science ( Cancer Science )  114 ( 3 ) 995 - 1006   2022年

DOI

Effects of ABCB1 polymorphisms on the transport of ponatinib into the cerebrospinal fluid in Japanese Philadelphia chromosome-positive acute lymphoblastic leukaemia patients

Fukushi Y.

British Journal of Clinical Pharmacology ( British Journal of Clinical Pharmacology )  89 ( 5 ) 1695 - 1700   2022年

The effects of polymorphisms of ABCB1 and ABCG2 on the dose-adjusted plasma trough concentrations and cerebrospinal fluid (CSF)-to-plasma ratios of ponatinib were evaluated. Blood (C4 ) and CSF (CSF4 ) concentrations at 4 h after administration were determined. The median (95% confidence interval) CSF4 -to-C4 ratio of ponatinib in subjects homozygous for ABCB1 variants 1236T/T, 2677T/T + T/A or 3435T/T were significantly higher than that in a group of subjects with other genotypes (P = .026, .012 and .015, respectively). The median (95% confidence interval) CSF4 -to-C4 ratio of ponatinib in 4 patients with the combination of ABCB1 variants 1236T/T-2677T/T + T/A-3435T/T was 2.62% (1.42-3.42%); this ratio was significantly higher than that in subjects with other genotypes (1.08% [0.89-1.47%]; P = .006). The brain distribution of ponatinib was affected by ABCB1 polymorphisms and therefore seems to be modulated by P-glycoprotein at the blood-brain and blood-CSF barriers.

DOI PubMed

Effects of SLC22A2 808G&gt;T polymorphism and bosutinib concentrations on serum creatinine in patients with chronic myeloid leukemia receiving bosutinib therapy

Abumiya M.

Scientific Reports ( Scientific Reports )  11 ( 1 ) 6362 - 6362   2021年12月

The purpose of this study was to investigate the effects of SLC22A2 808G>T polymorphism and trough concentrations (C0) of bosutinib on serum creatinine in 28 patients taking bosutinib. At 1, 3, 6, 12, 24, and 36 months after administration, analysis of bosutinib C0 and creatinine was performed at the same time of day. Significant correlations were observed between bosutinib C0 and the change rate of serum creatinine or the estimated glomerular filtration rate (eGFR; r = 0.328, P < 0.001 and r = - 0.315, P < 0.001, respectively). These correlations were particularly high in patients having the SLC22A2 808G/G genotype (r = 0.345 and r = - 0.329, respectively); however, in patients having the 808T allele, there were no significant differences. In multivariate analyses, the SLC22A2 808G/G genotype, patient age, bosutinib C0 and second-line or later bosutinib were independent factors influencing the change rate of creatinine. Bosutinib elevated serum creatinine through organic cation transporter 2 (OCT2). We observed a 20% increase in serum creatinine with a median bosutinib C0 of 63.4-73.2 ng/mL. Periodic measurement of serum creatinine after bosutinib therapy is necessary to avoid progression to severe renal dysfunction from simple elevation of creatinine mediated by OCT2 following bosutinib treatment.

DOI PubMed

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

Ochi Y.

Nature Communications ( Nature Communications )  12 ( 1 )   2021年12月

DOI

Regulatory t cell as a biomarker of treatment-free remission in patients with chronic myeloid leukemia

Fujioka Y.

Cancers ( Cancers )  13 ( 23 )   2021年12月

DOI

ANCA関連腎炎の臨床病理学的重症度と好中球細胞外トラップ

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

秋田腎不全研究会誌 ( 秋田腎不全研究会 )  24   19 - 27   2021年11月

Serial evaluation of the pharmacokinetics of ponatinib in patients with CML and Ph + ALL

Kawano N.

International Journal of Hematology ( International Journal of Hematology )  114 ( 4 ) 509 - 516   2021年10月

Although tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), intolerance and resistance to TKIs have been serious problems. Due to a lack of research, the importance of the pharmacokinetics (PK) of TKIs is currently unclear. We examined the PK of the third-generation TKI ponatinib to monitor side effects and efficacy during treatments for one patient with CML-chronic phase (CP-CML) and two who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), one for CML-blastic crisis (BC-CML) and one for Ph + ALL. The patient with CP-CML was intolerant to multiple TKIs (dasatinib, nilotinib, imatinib, and bosutinib) and thus was switched to ponatinib (15 mg/day). The patients who received allo-HSCT for BC-CML and Ph + ALL received ponatinib (15 mg/day) as maintenance therapy. Notably, serial evaluation of the PK of ponatinib showed that the median trough values (ng/ml) were 17.2 (12.2–34.5), 33.1 (21.2–40.3) and 27.7 (13.6–29.9) in patients 1, 2, and 3, respectively. These values were around the target concentration (23 ng/ml). All patients are maintaining complete remission without side effects. In conclusion, serial evaluation of PK of ponatinib may yield meaningful information about its safety and efficacy.

DOI PubMed

Multiple myeloma with t(11;14)-associated immature phenotype has lower CD38 expression and higher BCL2 dependence

Kitadate A.

Cancer Science ( Cancer Science )  112 ( 9 ) 3645 - 3654   2021年09月

DOI

IGL/MYC再構成を有し、かつCD138の発現を伴うB細胞性リンパ芽球性白血病(Precursor B-lymphoblastic leukemia with IGL/MYC rearrangement and CD138 expression)

倉橋 保奈実, 山下 鷹也, 北舘 明宏, 道下 吉広, 川端 良成, 北林 淳, 松本 奈津美, 齋藤 雅也, 小林 敬宏, 藤島 直仁, 亀岡 吉弘, 高橋 直人

日本血液学会学術集会 ( (一社)日本血液学会 )  83回   OS3 - 3   2021年09月

MYCの転座相手が非IgHと考えられるdouble hit lymphoma

安田 拓人, 亀岡 吉弘, 橋本 眞子, 藤岡 優樹, 斎藤 雅也, 鵜生川 久美, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  62 ( 9 ) 1417 - 1418   2021年09月

慢性リンパ性白血病に合併したmonoclonal immunotactoid glomerulopathy

齋藤 綾乃, 亀岡 吉弘, 小松田 敦, 鵜生川 久美, 今泉 ちひろ, 齋藤 雅也, 阿部 史人, 加賀 一, 奈良 瑞穂, 大谷 浩, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  63 ( 6-E ) 685 - 685   2021年09月

原発性マクログロブリン血症の経過観察中にMYD88陽性のびまん性大細胞型B細胞リンパ腫を発症した1例

高橋 照子, 倉橋 保奈実, 山下 鷹也, 齋藤 雅也, 小林 敬宏, 藤島 直人, 亀岡 吉弘, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  62 ( 9 ) 1418 - 1418   2021年09月

皮膚T細胞性リンパ腫においてmiR-26aの抑制はIL-22の過剰発現を介して転移に寄与する

松田 悠佳, 池田 翔, 北舘 明宏, 高橋 祐斗, 阿部 滉, 阿部 史人, 高橋 直人, 涌井 秀樹, 田川 博之

日本癌学会総会記事 ( (一社)日本癌学会 )  80回   [J14 - 5]   2021年09月

高腫瘍量濾胞性リンパ腫における治療前PET/CTを用いたTLGの予後予測因子としての有用性(Prognostic value of baseline total lesion glycolysis in high-tumor-burden follicular lymphoma)

黒木 航, 北舘 明宏, 山下 鷹也, 小林 敬宏, 池田 翔, 奈良 美保, 鵜生川 久美, 藤島 直仁, 吉岡 智子, 石山 公一, 亀岡 吉弘, 高橋 直人

日本血液学会学術集会 ( (一社)日本血液学会 )  83回   OS1 - 1   2021年09月

R-MPV療法を施行した中枢神経原発悪性リンパ腫の有効性と安全性の解析(The safety and efficacy of R-MPV therapy for untreated primary CNS lymphoma(PCNSL))

亀岡 吉弘, 阿部 滉, 山田 雅浩, 渡部 敦, 茂木 睦仁, 久米 正晃, 波多野 善明, 小笠原 仁, 高橋 直人

日本血液学会学術集会 ( (一社)日本血液学会 )  83回   OS1 - 4   2021年09月

ボスチニブ治療における血清クレアチニン値はボスチニブ血中トラフ濃度とSLC22A2遺伝子多型に影響される(Effect of SLC22A2 SNP and bosutinib concentrations on serum creatinine in patients taking bosutinib)

鐙屋 舞子, 高橋 直人, 高橋 さおり, 吉岡 智子, 亀岡 吉弘, 三浦 昌朋

日本血液学会学術集会 ( (一社)日本血液学会 )  83回   OS2 - 5   2021年09月

慢性骨髄性白血病急性転化におけるクローン進化および遺伝子異常と予後の解析(Clonal evolution and clinical impact of genetic lesions in blast crisis of chronic myeloid leukemia)

越智 陽太郎, 吉田 健一, 南谷 泰仁, 佐々木 光, 三谷 絹子, 細谷 紀子, 平本 展大, 石川 隆之, 大屋敷 一馬, 高橋 直人, 高久 智生, 土屋 俊, 兼村 信宏, 中村 信彦, 上田 恭典, 吉原 哲, 塩澤 裕介, 趙 蘭英, 竹田 淳恵, 綿谷 陽作, 奥田 瑠璃花, 牧島 秀樹, 白石 友一, 千葉 健一, 田中 洋子, 真田 昌, 高折 晃史, 宮野 悟, Shih Lee-Yung, 小川 誠司

日本血液学会学術集会 ( (一社)日本血液学会 )  83回   OS1 - 1   2021年09月

慢性骨髄性白血病急性転化のクローン進化および遺伝子異常と予後

越智 陽太郎, 吉田 健一, 南谷 泰仁, 佐々木 光, 三谷 絹子, 細谷 紀子, 石川 隆之, 大屋敷 一馬, 高橋 直人, 塩澤 裕介, 牧島 秀樹, 白石 友一, 真田 昌, 高折 晃史, 宮野 悟, 小川 誠司

日本癌学会総会記事 ( (一社)日本癌学会 )  80回   [E14 - 1]   2021年09月

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年09月

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年09月

濾胞性リンパ腫におけるリツキシマブ維持療法の長期生存 東北血液フォーラム前向き多施設共同研究結果(Long-term survival in patients with follicular lymphoma following Rituximab maintenance in THF-19)

大本 英次郎, 妻沼 りこ, 熊谷 裕昭, 相澤 桂子, 吉田 こず恵, 池田 和彦, 亀岡 吉弘, 石澤 賢一, 張替 秀郎, 高橋 直人

日本血液学会学術集会 ( (一社)日本血液学会 )  83回   BPA - 6   2021年09月

Il-6 generated from human hematopoietic stem and progenitor cells through tlr4 signaling promotes emergency granulopoiesis by regulating transcription factor expression

Sasaki Y.

Journal of Immunology ( Journal of Immunology )  207 ( 4 ) 1078 - 1086   2021年08月

Emergency granulopoiesis, also known as demand-adapted granulopoiesis, is defined as the response of an organism to systemic bacterial infections, and it results in neutrophil mobilization from reservoir pools and increased myelopoiesis in the bone marrow. Indirect and direct initiating mechanisms of emergency granulopoiesis have been hypothesized. However, the detailed mechanism of hyperactive myelopoiesis in the bone marrow, which leads to granulocyte left shift, remains unknown. In this study, we report that TLR4 is expressed on granulo-monocytic progenitors, as well as mobilized human peripheral blood CD34+ cells, which account for 0.2% of monocytes in peripheral blood, and ∼ 10% in bone marrow. LPS, a component of Gram-negative bacteria that results in a systemic bacterial infection, induces the differentiation of peripheral blood CD34+ cells into myelocytes and monocytes in vitro via the TLR4 signaling pathway. Moreover, CD34+ cells directly responded to LPS stimulation by activating the MAPK and NF-κB signaling pathways, and they produced IL-6 that promotes emergency granulopoiesis by phosphorylating C/EBPα and C/EBPβ, and this effect was suppressed by the action of an IL-6 receptor inhibitor. This work supports the finding that TLR is expressed on human hematopoietic stem and progenitor cells, and it provides evidence that human hematopoietic stem and progenitor cells can directly sense pathogens and produce cytokines exerting autocrine and/or paracrine effects, thereby promoting differentiation.

DOI PubMed

血液形態診断のためのケースカンファレンス Cryptic translocationを認めたPML-RARA陽性微細顆粒型急性前骨髄球性白血病

菊地 優子, 山下 鷹也, 小林 敬宏, 永沼 綾子, 齊藤 由紀子, 安保 綾奈, 荒井 杏子, 富谷 陽子, 高橋 直人, 植木 重治

日本検査血液学会雑誌 ( (一社)日本検査血液学会 )  22 ( 2 ) 263 - 269   2021年07月

症例は50歳代男性。職場の健診にて白血球増多を指摘され当院紹介となった。受診の2日前より発熱、頭痛あり、また最近誘因無く四肢に紫斑が出現することを自覚していた。受診時の血液検査所見として、白血球著増、貧血、血小板減少、線溶亢進型播種性血管内凝固症候群を認めた。末梢血液像は、核網繊細で核形不整が顕著な単球様細胞で占められており、僅かにアズール顆粒が豊富な細胞やファゴット細胞を認めた。骨髄像は末梢血と同様の異常細胞で占められており、細胞表面マーカーでは、CD2、CD13、CD33、CD117、MPOが陽性、CD34、CD56、HLA-DRが陰性であった。染色体検査は正常核型であったが、遺伝子検査ではPML-RARA融合遺伝子を認めたことから、cryptic translocationを認めたPML-RARA陽性微細顆粒型急性前骨髄球性白血病の診断に至った。本症例のように線溶亢進型播種性血管内凝固症候群と白血病細胞の増多を認めるが、典型的な急性前骨髄球性白血病細胞をほとんど認めない場合は、微細顆粒型急性前骨髄球性白血病を鑑別に挙げ、全トランス型レチノイン酸による治療を遅滞なく行うことが重要である。(著者抄録)

抗がん剤起因性の肝類洞閉塞症候群に対し、デフィブロチドが著効したB細胞性リンパ腫

倉橋 保奈実, 山下 鷹也, 齋藤 雅也, 藤島 直仁, 亀岡 吉弘, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  62 ( 4 ) 323 - 323   2021年04月

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

PCd療法により維持透析を離脱し完全寛解を達成したpenta-refractory IgD-λ型多発性骨髄腫

池田 翔, 山田 雅浩, 黒木 航, 齋藤 綾乃, 藤岡 優樹, 鵜生川 久美, 亀岡 吉弘, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  61 ( 4 ) 420 - 420   2020年04月

R-CHOP療法に奏効しているGCB typeのdouble expressor lymphoma(DEL)

山田 雅浩, 亀岡 吉弘, 鵜生川 久美, 齋藤 綾乃, 藤岡 優樹, 池田 翔, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  61 ( 4 ) 419 - 419   2020年04月

CD7-Positive Diffuse Large B-Cell Lymphoma Presenting as an Intranasal Tumor.

Kazuaki Teshima, Masaaki Kume, Yasushi Kawaharada, Takashi Saito, Ko Abe, Sho Ikeda, Hideaki Ohyagi, Megumi Zuguchi, Masashi Zuguchi, Yosuke Kubota, Yoshitaka Enomoto, Masahito Miura, Satsuki Takahashi, Masahiro Saito, Ken Saito, Naoto Takahashi

Case reports in hematology   2020   1514729 - 1514729   2020年

We report a case of a 74-year-old man with a cluster of differentiation (CD) 7-positive diffuse large B-cell lymphoma (DLBCL) in the right nasal cavity. Flow cytometry analyses showed CD7 and CD20 positivity in tumor cells. The patient received 6 cycles of R-CHOP plus local radiation therapy because positron emission tomography-computed tomography after R-CHOP revealed an intranasal lesion. The patient achieved complete remission (CR) after radiation therapy. The frequency of CD7-positive DLBCL is rare, and only 11 cases with follow-up of clinical course have been reported thus far. CR or partial response was noted in 8 of 11 cases after receiving rituximab combined with chemotherapy. In total, 9 of 12 cases involved the development of extranodal lesions, which occurred as an intranasal tumor in 3 cases. It is important to examine the clinical features by accumulation of further cases.

DOI PubMed

多発性骨髄腫においてCD38低発現はt(11;14)転座及びBCL2依存性に関連する

北舘明宏, 北舘明宏, 池田翔, 成田健太郎, 三浦大典, 寺尾俊紀, 津島隆史, 竹内正美, 高橋直人, 末永孝生

日本血液学会学術集会抄録(Web)   82nd   2020年

J-GLOBAL

コントロール不良な高齢発症関節リウマチに後天性血友病を合併した一例

今泉 ちひろ, 阿部 史人, 齋藤 綾乃, 齋藤 雅也, 藤岡 優樹, 奈良 瑞穂, 郭 永梅, 奈良 美保, 小澤 政豊, 吉岡 智子, 小松田 敦, 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 )  29回   86 - 86   2019年11月

B-ALL移植後再発症例におけるblinatumomabの治療反応性と免疫プロファイル

小林 敬宏, 鵜生川 久美, 藤島 眞澄, 亀岡 吉弘, 藤島 直仁, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  60 ( 11 ) 1596 - 1597   2019年11月

器質化肺炎と肥厚性硬膜炎にて発症した難治性IgG4関連疾患

阿部 史人, 斎藤 綾乃, 斎藤 雅也, 奈良 瑞穂, 郭 永梅, 奈良 美保, 吉岡 智子, 小松田 敦, 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 )  29回   89 - 89   2019年11月

Effect of low platelet HLA-C expression on donor-specific antibody depletion following platelet transfusion from a corresponding HLA donor

Yamashita T.

Bone Marrow Transplantation ( Bone Marrow Transplantation )  54 ( 10 ) 1713 - 1716   2019年10月

DOI PubMed

ヘキソキナーゼ-2は低酸素誘導性オートファジーを促進し、多発性骨髄腫のプロテアソーム阻害薬抵抗性を誘導する(Hexokinase-2(HK2) promotes hypoxia-inducible autophagy, leading to proteasome inhibitor resistance in multiple myeloma)

池田 翔, 阿部 史人, 北舘 明宏, 高橋 直人, 田川 博之

日本癌学会総会記事 ( 日本癌学会 )  78回   J - 1016   2019年09月

IgA-associated glomerulonephritis with MPGN-like patternの13症例

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

日本腎臓学会誌 ( (一社)日本腎臓学会 )  61 ( 6 ) 741 - 741   2019年08月

T細胞リンパ腫の腎浸潤で半月体性腎炎を来した1例

澤村 昌人, 畠山 卓, 斎藤 綾乃, 斎藤 雅也, 小松田 敦, 涌井 秀樹, 城 謙輔, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  61 ( 6 ) 725 - 725   2019年08月

被疑薬中止4週後のステロイド治療が奏功した薬剤性間質性腎炎

齋藤 雅也, 今泉 ちひろ, 齋藤 綾乃, 阿部 史人, 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 )  61 ( 6 ) 734 - 734   2019年08月

ANCA関連腎炎の組織学的重症度と血清シトルリン化ヒストンH3濃度の関連についての検討

齋藤 雅也, 齋藤 綾乃, 阿部 史人, 加賀 一, 澤村 昌人, 奈良 瑞穂, 佐藤 隆太, 小松田 敦, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  61 ( 3 ) 347 - 347   2019年05月

IgA腎症における臨床的予後影響因子とOxford分類2016と日本分類2013の関連性についての検証

佐藤 隆太, 齋藤 雅也, 阿部 史人, 奈良 瑞穂, 奥山 慎, 小松田 敦, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  61 ( 3 ) 287 - 287   2019年05月

進行性ループス腎炎III型、IV型の現状と課題

阿部 史人, 齋藤 雅也, 奈良 瑞穂, 佐藤 隆太, 奥山 慎, 小松田 敦, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  61 ( 3 ) 345 - 345   2019年05月

Dasatinib and low-intensity chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukemia in a child with Down syndrome

Hirabayashi S.

Pediatric Blood and Cancer ( Pediatric Blood and Cancer )  66 ( 5 ) e27612   2019年05月

DOI PubMed

Hexokinase-2(HK2)は低酸素誘導性オートファジーを制御し骨髄腫細胞のプロテアソーム阻害薬耐性に寄与する(Hexokinase-2(HK2) regulates hypoxia-induced autophagy, leading to resistance of proteasome inhibitor of multiple myeloma)

池田 翔, 阿部 史人, 北舘 明宏, 小林 敬宏, 高橋 直人, 田川 博之

International Journal of Myeloma ( 日本骨髄腫学会 )  9 ( 1 ) 83 - 83   2019年05月

好酸球増多疾患・好酸球性肺炎 著明な組織内シャルコー・ライデン結晶を認めた好酸球増多症候群患者

福地 峰世, 植木 重治, 山本 洋平, 奈良 美保, 今野 泰典, 面川 歩, 嵯峨 知生, 守時 由起, 大森 泰文, 高橋 直人, 廣川 誠

アレルギー ( (一社)日本アレルギー学会 )  68 ( 4-5 ) 529 - 529   2019年05月

リンパ腫の病勢とANCAの増減に関連を認めたPR3-ANCA陽性CD5陽性びまん性大細胞型B細胞性リンパ腫

阿部 滉, 佐藤 隆太, 渡部 敦, 藤島 眞澄, 藤島 直仁, 亀岡 吉弘, 高橋 直人, 大田 泰徳

臨床血液 ( (一社)日本血液学会-東京事務局 )  60 ( 4 ) 336 - 337   2019年04月

皮膚限局型IVLBCLで発症し、Asian variant様IVLBCLの臨床像で再発したaggressive B-cell lymphoma

高橋 凪, 郭 永梅, 阿部 史人, 山下 鷹也, 奈良 美保, 吉岡 智子, 亀岡 吉弘, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  60 ( 4 ) 332 - 332   2019年04月

Pharmacokinetics of Tacrolimus Coadministered With Letermovir in Allogeneic Hematopoietic Stem Cell Transplantation Patients

Guo Y.m.

Clinical Pharmacology in Drug Development ( Clinical Pharmacology in Drug Development )  8 ( 3 ) 411 - 412   2019年04月

DOI PubMed

Membranous nephropathy with solitary polyclonal IgA deposition: A case report and literature review.

Masato Sawamura, Atsushi Komatsuda, Hajime Kaga, Ayano Saito, Tadashi Yasuda, Hideki Wakui, Kensuke Joh, Naoto Takahashi

Clinical nephrology. Case studies   7   60 - 65   2019年

A 60-year-old man presented with nephrotic syndrome (NS). Light microscopy of renal biopsy specimens showed minor glomerular abnormalities, while immunofluorescence microscopy revealed solitary polyclonal granular IgA deposition along the glomerular capillary walls. Electron microscopy showed small amounts of electron-dense deposits in the subepithelial area, but not in the mesangial area. In this patient, apparent underlying disease was not found during the 3-year follow-up, and low-dose prednisolone was effective in the treatment of NS. To our knowledge, there is only one case report of membranous nephropathy with clinicopathological features similar to our case.

DOI PubMed

Different clonal dynamics of chronic myeloid leukaemia between bone marrow and the central nervous system

Ogawa M.

British Journal of Haematology ( British Journal of Haematology )  183 ( 5 ) 842 - 845   2018年12月

DOI PubMed

出血傾向で発症した第X因子欠乏を伴うALアミロイドーシス(Primary hepatic amyloidosis with factor X deficiency)

高橋 凪, 郭 永梅, 阿部 史人, 山下 鷹也, 奈良 美保, 吉岡 智子, 伊藤 行信, 吉田 誠, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 9 ) 1669 - 1669   2018年09月

ニボルマブ投与後に筋炎を発症したホジキンリンパ腫(Nivolumab-related myositis in Hodgkin's lymphoma)

郭 永梅, 小林 敬宏, 山下 鷹也, 奈良 美保, 鵜生川 久美, 渡部 敦, 藤島 眞澄, 藤島 直仁, 吉岡 智子, 亀岡 吉弘, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 9 ) 1737 - 1737   2018年09月

ABCB1遺伝子多型は多発性骨髄腫患者におけるレナリドミドの薬物動態に影響を与える(ABCB1 polymorphism influence the pharmacokinetics of lenalidomide in patients with multiple myeloma)

小林 敬宏, 鐙屋 舞子, 赤嶺 由美子, 伊藤 史子, 志田 青慈, 三浦 昌朋, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 9 ) 1624 - 1624   2018年09月

CMLにおけるボスチニブの血中濃度と有害事象の関連性(Correlation of plasma concentration and adverse events of bosutinib in chronic myeloid leukemia)

三田 亜紀子, 鐙屋 舞子, 三浦 昌朋, 高橋 沙織, 吉岡 智子, 亀岡 吉弘, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 9 ) 1703 - 1703   2018年09月

再発難治CLL/SLL, MCLに対するイブルチニブの有効性と安全性(The safety and efficacy of ibrutinib for relapsed/refractory MCL and CLL/SLL)

亀岡 吉弘, 北林 淳, 鵜生川 久美, 野口 晋佐, 大八木 秀明, 茂木 睦仁, 川端 良成, 小笠原 仁, 黒木 淳, 仁村 隆, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 9 ) 1602 - 1602   2018年09月

CML患者のボスチニブ血中濃度におけるNR1/2, CYP3A4およびABCトランスポーター遺伝子多型の影響(Effects of polymorphisms in NR1I2, CYP3A4, and ABC transporters on the concentrations of bosutinib)

鐙屋 舞子, 三田 亜紀子, 吉岡 智子, 亀岡 吉弘, 高橋 直人, 三浦 昌朋

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 9 ) 1532 - 1532   2018年09月

INCREASED MEAN PLATELET VOLUME (MPV) AS A POTENTIAL PREDICTOR OF THROMBOPOIETIC RECOVERY FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANTATION OR CHEMOTHERAPY

Yuko Kikuchi, Ayako Naganuma, Kana Haseyama, Kyoko Ono, Takeshi Kobayashi, Noriko Kobayashi, Ayumi Omokawa, Tomoo Saga, Shigeharu Ueki, Naoto Takahashi, Hironobu Shimizu, Makoto Hirokawa

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY ( WILEY )  40   68 - 69   2018年09月

研究発表要旨（国際会議）  

秋田県内の多施設調査による骨髄異形成症候群に対するアザシチジンの使用状況と安全性/有効性に関する検討(Azacitidine safety and efficacy in Myelodysplastic syndrome: A multicenter survey in Akita)

渡部 敦, 吉岡 智子, 伊藤 史子, 池田 翔, 郭 永梅, 奈良 美保, 藤島 眞澄, 藤島 直仁, 市川 善一, 中山 豊, 川端 良成, 北林 淳, 桑山 明久, 小笠原 仁, 井上 武, 茂木 睦仁, 仁村 隆, 三田 亜紀子, 道下 吉広, 波多野 善明, 伊藤 貢, 黒木 淳, 手島 和明, 大八木 秀明, 久米 正晃, 野口 晋佐, 鵜生川 久美, 亀岡 吉弘, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 9 ) 1780 - 1780   2018年09月

解糖系遺伝子HK2は骨髄低酸素微小環境に存在する骨髄腫細胞に対する治療標的となりうる(A glycolytic gene HK2 as a therapeutic target of myeloma cells in hypoxic microenvironment)

池田 翔, 北舘 明宏, 阿部 史人, 高橋 直人, 田川 博之

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 9 ) 1611 - 1611   2018年09月

成人特発性血小板減少症におけるIGHV4-28/IGHJ4再構成由来IgG型B細胞抗原受容体の高発現(Overexpression of the rearranged IGHV4-28//IGHJ4 gene-derived IgG B-cell receptors in adult ITP)

藤島 直仁, 富樫 賢, 長谷川 諒, 渡部 健, 嵯峨 亜希子, 面川 歩, 嵯峨 知生, 植木 重治, 高橋 直人, 北浦 一孝, 鈴木 隆二, 廣川 誠

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 9 ) 1579 - 1579   2018年09月

腸炎を契機に発症した横紋筋融解に伴う急性腎障害

齋藤 雅也, 渡邊 春佳, 阿部 史人, 池田 翔, 奈良 瑞穂, 鵜生川 久美, 佐藤 隆太, 奥山 慎, 亀岡 吉弘, 小松田 敦, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  60 ( 6 ) 902 - 902   2018年08月

[Chronic myeloid leukemia: state-of-the-art management].

Takahashi N

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 一般社団法人 日本血液学会 )  59 ( 6 ) 747 - 754   2018年06月

<p>慢性期慢性骨髄性白血病の新たな治療目標である無治療寛解（treatment-free remission, TFR）とはチロシンキナーゼ阻害剤（tyrosine kinase inhibitor, TKI）により深い分子遺伝学的寛解（deep molecular response, DMR）に到達したのち，TKI治療を中止しても分子遺伝学的効果が維持される状態のことである。2017年のNCCNガイドラインでは「3年以上のTKI治療歴，2年以上のDMRの維持，TKI中止後半年間の月一回の分子遺伝学的モニタリングの実施とその後の定期的なモニタリングなど」の一定の条件を課して臨床試験以外でのTKI中止を世界で初めて許容した。本邦のガイドラインにおいても今後，臨床試験外のTFRが言及されると推測される。将来のTFRを成功させるため，少なくともDMRを達成し継続することが，TKI感受性を示す症例の課題である。</p>

DOI PubMed CiNii Research

The potential role of clarithromycin addition to lenalidomide and dexamethasone therapy (BiRd) in multiple myeloma

Kobayashi T.

Annals of Hematology ( Annals of Hematology )  97 ( 6 ) 1097 - 1099   2018年06月

DOI PubMed

特集 急性白血病の薬物療法のupdate ～最新の診断・治療戦略～ ８.治療薬物モニタリング

三浦昌朋, 高橋直人

医薬ジャーナル ( 医薬ジャーナル社 )  54 ( 5 ) 1244 - 1248   2018年05月

DOI CiNii Research

【急性白血病の薬物療法のupdate 〜最新の診断・治療戦略〜】治療薬物モニタリング(therapeutic drug monitoring:TDM)

三浦 昌朋, 高橋 直人

医薬ジャーナル ( (株)医薬ジャーナル社 )  54 ( 5 ) 1244 - 1248   2018年05月

治療への基礎的アプローチ 骨髄腫微小環境で発現上昇する解糖系遺伝子群の治療標的としての可能性

池田 翔, 北舘 明宏, 阿部 史人, 小林 敬宏, 高橋 直人, 田川 博之

International Journal of Myeloma ( 日本骨髄腫学会 )  8 ( 2 ) 92 - 92   2018年05月

J-GLOBAL

治療への基礎的アプローチ 骨髄腫微小環境で発現上昇する解糖系遺伝子群の治療標的としての可能性

池田 翔, 北舘 明宏, 阿部 史人, 小林 敬宏, 高橋 直人, 田川 博之

International Journal of Myeloma ( 日本骨髄腫学会 )  8 ( 2 ) 92 - 92   2018年05月

ANCA関連血管炎における末梢血単核球でのToll-like receptors mRNA発現の検討

齋藤 綾乃, 加賀 一, 阿部 史人, 齋藤 雅也, 奈良 瑞穂, 佐藤 隆太, 奥山 慎, 小松田 敦, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  60 ( 3 ) 374 - 374   2018年04月

特発性膜性腎症における抗PLA2R抗体の経時的推移の検討

阿部 史人, 澤村 昌人, 齋藤 綾乃, 齋藤 雅也, 加賀 一, 小澤 政豊, 大谷 浩, 奥山 慎, 小松田 敦, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  60 ( 3 ) 370 - 370   2018年04月

特集 血液疾患における薬剤の副作用とその対策 １.チロシンキナーゼ阻害薬での対策１)末梢動脈閉塞性疾患(PAOD)(ニロチニブ)

吉岡智子, 高橋直人

血液フロンティア ( 医薬ジャーナル社 )  28 ( 5 ) 673 - 679   2018年04月

DOI CiNii Research

著明な白血球増多を伴い急速な病状進行と多臓器障害を呈したG-CSF産生ALK陽性ALCL

渡部 敦, 阿部 史人, 奈良 美保, 鵜生川 久美, 藤島 眞澄, 吉岡 智子, 藤島 直仁, 亀岡 吉弘, 高橋 直人, 菅沢 邦江

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 4 ) 449 - 449   2018年04月

Rituximab療法により5年以上寛解を維持しているCD20陽性リンパ増殖性疾患関連後天性von Willebrand症候群

倉橋 保奈実, 川端 良成, 道下 吉広, 北林 淳, 小林 敬宏, 北舘 明宏, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  59 ( 4 ) 420 - 425   2018年04月  [査読有り]

膜型PGNMIDにおける抗PLA2R抗体の検討

澤村 昌人, 小松田 敦, 阿部 史人, 涌井 秀樹, 朝倉 健一, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  60 ( 3 ) 409 - 409   2018年04月

学会印象記 第59回 米国血液学会議(ASH2017)

池田翔, 髙橋直人

血液フロンティア ( 医薬ジャーナル社 )  28 ( 4 ) 608 - 611   2018年03月

DOI CiNii Research

Tubulointerstitial nephritis with IgM-positive plasma cells

Takahashi N.

Journal of the American Society of Nephrology ( Journal of the American Society of Nephrology )  28 ( 12 ) 3688 - 3698   2017年12月

DOI

BCL2、BCL6、MYC遺伝子転座を認めた治療抵抗性triple hit follicular lymphoma

池田 翔, 亀岡 吉弘, 斎藤 綾乃, 小林 五十鈴, 鵜生川 久美, 山下 鷹也, 奈良 美保, 郭 永梅, 渡部 敦, 藤島 眞澄, 藤島 直仁, 吉岡 智子, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  58 ( 12 ) 2473 - 2473   2017年12月

High-Throughput Sequencing of IgG B-Cell Receptors Reveals the Frequent Usage of the Rearranged IGHV4-28//IGHJ4 Gene in Primary Immune Thrombocytopenia in Adults

Naohito Fujishima, Masaru Togashi, Ryo Hasegawa, Ken Watanabe, Akiko Saga, Ayumi Omokawa, Tomoo Saga, Shigeharu Ueki, Naoto Takahashi, Kazutaka Kitaura, Ryuji Suzuki, Makoto Hirokawa

BLOOD ( AMER SOC HEMATOLOGY )  130   2017年12月

研究発表要旨（国際会議）  

0

Histone Deacetylase Inhibitors Downregulate CCR4 Expression and Decrease Mogamulizumab Efficacy in CCR4-Positive Mature T-Cell Lymphomas

Kitadate Akihiro, Ikeda Sho, Abe Fumito, Takahashi Naoto, Shimizu Norio, Matsue Kosei, Tagawa Hiroyuki

BLOOD   130   2017年12月

Hypoxia-Inducible KDM3A Addiction in Multiple Myeloma

Ikeda Sho, Kitadate Akihiro, Abe Fumito, Takahashi Naoto, Tagawa Hiroyuki

BLOOD   130   2017年12月

半月体を形成する糖尿病性腎症の臨床病理学的検討

齋藤 綾乃, 加賀 一, 齋藤 雅也, 阿部 史人, 奈良 瑞穂, 富樫 賢, 小松田 敦, 涌井 秀樹, 高橋 直人

秋田腎不全研究会誌 ( 秋田腎不全研究会 )  20   43 - 47   2017年11月

腎生検で診断した糖尿病性腎症患者を対象とし、半月体形成を伴う群20例(男性16例、女性4例、36.0〜81.0歳)、伴わない群43例(男性31例、女性12例、18.5〜40.8歳)であった。腎生検時の年齢、BMI、血圧、尿蛋白、尿潜血、eGFR、HbA1c、総コレステロール値、C-reactive protein、糖尿病性網膜症の有無、降圧薬内服の有無、および腎予後について調査した。腎予後は透析導入をエンドポイントとした。臨床データは全ての項目で2群間に有意差を認めなかった。病理学的所見では糸球体病変がClass III(結節病変を伴う糸球体)の割合が半月体形成群で有意に高く、糸球体基底膜のIgG沈着も半月体形成群で有意に高かった。腎生存率は2群間で有意差を認めなかった。

Relationship between the CYP2C19 Phenotype Using the Voriconazole-to-Voriconazole N -Oxide Plasma Concentration Ratio and Demographic and Clinical Characteristics of Japanese Patients with Different CYP2C19 Genotypes

Niioka T.

Therapeutic Drug Monitoring ( Therapeutic Drug Monitoring )  39 ( 5 ) 514 - 521   2017年10月

DOI

Relationship Between the CYP2C19 Phenotype Using the Voriconazole-to-Voriconazole N-Oxide Plasma Concentration Ratio and Demographic and Clinical Characteristics of Japanese Patients With Different CYP2C19 Genotypes

Takenori Niioka, Naohito Fujishima, Maiko Abumiya, Takaya Yamashita, Kumi Ubukawa, Miho Nara, Masumi Fujishima, Naoto Takahashi, Masatomo Miura

THERAPEUTIC DRUG MONITORING ( LIPPINCOTT WILLIAMS & WILKINS )  39 ( 5 ) 514 - 521   2017年10月

Background: Although voriconazole (VRCZ) is metabolized to VRCZ N-oxide principally by CYP2C19, VRCZ clearance is affected by multiple factors. In this study, we investigated the relationship between the CYP2C19 phenotype using the VRCZ-to-VRCZ N-oxide plasma concentration ratio (VRCZ/N-oxide) and demographic and clinical characteristics of Japanese patients taking VRCZ.
Methods: A total of 65 Japanese patients taking VRCZ for prophylaxis or treatment of fungal infection were enrolled in this study. Stepwise selection multiple linear regression analysis was performed to investigate the effect of factors on the VRCZ/N-oxide ratio.
Results: In patients not undergoing concurrent treatment with a drug influencing CYP2C19 activity (n = 54), the VRCZ/N-oxide ratio with definite thresholds for CYP2C19 genotypes, CYP2C19*1/ *1, *1/*2 + *1/*3 + *2/*17, and *2/*2 + *2/*3, was specifically identified in patients taking VRCZ (&lt;0.48, &gt;= 0.48, and &lt;0.82 and &gt;= 0.82). However, the VRCZ/N-oxide ratio could not be predicted based solely on the CYP2C19 genotype (R-2 = 0.053). The route of VRCZ administration, C-reactive protein concentration determined on the same day as VRCZ plasma concentration measurement, CYP2C19 extensive metabolizer, and patient age were independent factors influencing the VRCZ/N-oxide ratio (R-2 = 0.489, standard-ized regression coefficient = 0.385, 0.380, 20.231, and 0.231; P = 0.001, 0.001, 0.032, and 0.036, respectively).
Conclusions: It is possible to comprehensively evaluate CYP2C19 activity using the actual measured value of the VRCZ/N-oxide ratio in patients taking VRCZ. The predictive performance of the VRCZ/ N-oxide ratio was improved by including the route of administration, C-reactive protein level, and patient age in addition to the CYP2C19 genotype as predictive factors.

Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation

Doki N.

Annals of Hematology ( Annals of Hematology )  96 ( 9 ) 1517 - 1523   2017年09月

Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (&lt;2), intermediate (2, 3), and high (&gt;3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p &lt; 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.

DOI PubMed

Long-term treatment with bosutinib in a phase 1/2 study in Japanese chronic myeloid leukemia patients resistant/intolerant to prior tyrosine kinase inhibitor treatment

Takahashi N.

International Journal of Hematology ( International Journal of Hematology )  106 ( 3 ) 398 - 410   2017年09月

This long-term follow-up of a completed phase 1/2 study assessed the safety and efficacy of bosutinib in Japanese Philadelphia chromosome-positive, chronic phase (CP) or advanced phase (ADV) chronic myeloid leukemia patients who were resistant/refractory or intolerant to prior tyrosine kinase inhibitor treatment. This analysis included 63 patients with a median bosutinib follow-up of 132 weeks (range 3aEuro'372). In the CP second-line (2L) cohort, the cumulative major cytogenetic response (MCyR) and major molecular response (MMR) rates throughout the study were 73 and 53%, respectively. In the CP third-line (3L) cohort, the cumulative MCyR and MMR rates throughout the study were 70 and 40%, respectively. Of the eight ADV patients, MCyR was attained or maintained by 50% of patients, and complete hematologic response was attained or maintained by 25% of patients. Progression-free survival rate and overall survival rate at 96 weeks were, respectively, 91 and 98% in CP2L, 88 and 100% in CP3L, and 33 and 50% in ADV patients. The most common adverse events (&gt; 50%) reported were diarrhea (95%), nasopharyngitis (57%), and rash (57%). Bosutinib demonstrated durable efficacy and a manageable tolerability profile over long-term use in Japanese patients.
ClinicalTrials.gov: NCT00811070.

DOI

Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study

Tojo A.

International Journal of Hematology ( International Journal of Hematology )  106 ( 3 ) 385 - 397   2017年09月

In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2). MCyR was achieved/maintained by 12 months in 65% of CP-CML patients
MaHR was achieved by 6 months in 61% of patients with advanced phase disease. The most common nonhematologic grade 3/4 treatment-emergent adverse event (AE) was hypertension (37%)
common hematologic grade 3/4 AEs were thrombocytopenia (57%), neutropenia (34%), and leukopenia (26%). Overall, five (14%) patients experienced arterial occlusive events (AOEs)
no grade 5 AOEs were reported. The steady-state accumulation ratio of ponatinib (based on area under the curve) ranged from 2.6 (15 mg/day) to 1.3 (45 mg/day). In summary, ponatinib demonstrated efficacy in Japanese patients with CML and Ph+ALL resistant/intolerant to prior TKI treatment
safety data support a recommended starting dose of 45 mg/day in these patients.

DOI PubMed

Quantification of interstitial fibrosis in renal allografts and clinical correlates of long-Term graft function

Nara M.

American Journal of Nephrology ( American Journal of Nephrology )  46 ( 3 ) 187 - 194   2017年09月

DOI

T細胞リンパ腫においてHDAC阻害剤はCCR4発現を減少させモガムリズマブの作用を減弱させる

北舘 明宏, 池田 翔, 阿部 史人, 手島 和暁, 高橋 直人, 末永 孝生, 田川 博之

日本癌学会総会記事 ( 日本癌学会 )  76回   E - 2025   2017年09月

低酸素環境における骨髄腫細胞の生存はH3K9脱メチル化酵素KDM3Aに依存する

池田 翔, 北舘 明宏, 阿部 史人, 高橋 直人, 田川 博之

日本癌学会総会記事 ( 日本癌学会 )  76回   J - 3036   2017年09月

悪性リンパ腫におけるイノシトールリン脂質プロファイル

阿部 史人, 中西 広樹, 北舘 明宏, 池田 翔, 亀岡 吉弘, 高橋 直人, 佐々木 雄彦, 田川 博之

日本癌学会総会記事 ( 日本癌学会 )  76回   P - 2236   2017年09月

早期LCDDに対してVRD療法が奏功した一例

齋藤 綾乃, 池田 翔, 伊藤 香里, 阿部 史人, 奈良 瑞穂, 奥山 慎, 涌井 秀樹, 小松田 敦, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  59 ( 6 ) 893 - 893   2017年09月

Ph陽性ALLに対するチロシンキナーゼ阻害剤の役割と臨床効果 (特集 急性リンパ芽球性白血病(ALL)の病態と診療 : 最近の展開)

山下 鷹也, 髙橋 直人

血液内科 = Hematology ( 科学評論社 )  75 ( 3 ) 287 - 293   2017年09月

CiNii Research

CPC解説(第97回) 両肺に多発肺腫瘤を形成した若年成人発症菌状息肉症の一剖検例

伊藤 行信, 吉田 誠, 馬越 通信, 前田 大地, 高橋 啓, 郭 永梅, 高橋 直人, 後藤 明輝

病理と臨床 ( (株)文光堂 )  35 ( 8 ) 759 - 765   2017年08月

Optical properties of a dichroic dye-doped liquid-crystal grating and its application to optical rotation measurement

Honma M.

Applied Optics ( Applied Optics )  56 ( 21 ) 5849 - 5856   2017年07月

DOI

同種造血幹細胞移植前にruxolitinibで脾腫のコントロールを行った多血症線維化期から移行した急性骨髄性白血病

藤島 眞澄, 藤島 直仁, 北舘 明宏, 郭 永梅, 渡部 敦, 鵜生川 久美, 奈良 美保, 吉岡 智子, 亀岡 吉弘, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  58 ( 7 ) 743 - 748   2017年07月

症例は64歳女性(移植時年齢)。移植の7年前に真性多血症(JAK2 V617F変異陽性)と診断,2年前に脾腫が増悪しruxolitinibを開始した。汎血球減少のためruxolitinibを中止したところ,脾臓の増大と骨髄線維化を伴う白血化を認め,多血症後線維化期から移行した急性骨髄性白血病と診断した。寛解導入療法により完全寛解が得られたが,脾臓は季肋下8横指触知する状態であった。地固め療法2コース後にruxolitinibを再投与し,脾臓が縮小した時点で非血縁ドナーから末梢血幹細胞移植を行った。Ruxolitinibは移植前日まで継続した。Day 13に好中球生着が得られた後,withdrawal symptomと考えられる脾臓の再増大がみられたが一時的であった。脾腫は同種造血幹細胞移植における生着不全・移植関連死のリスク因子となるが,移植前の摘脾や照射は侵襲性が問題となる。Ruxolitinibは脾腫を非侵襲的に改善するため,移植前まで継続することにより,脾臓の縮小による生着率の向上が期待される。(著者抄録)

Clinicopathological characteristics of malignant lymphoma in patients with hepatitis C virus infection in the Tohoku district in Eastern Japan

Tajima K.

Leukemia and Lymphoma ( Leukemia and Lymphoma )  58 ( 6 ) 1509 - 1511   2017年06月

DOI

虚血性持続勃起症(Priapism)を契機に発見された急性骨髄性白血病とWaldenstrom's-macroglobulinemiaの重複例

永沼 綾子, 菊地 優子, 長谷山 佳菜, 小野 杏子, 小林 毅, 小林 則子, 北舘 明宏, 亀岡 吉弘, 高橋 直人, 廣川 誠

日本検査血液学会雑誌 ( (一社)日本検査血液学会 )  18 ( 学術集会 ) S182 - S182   2017年06月

J-GLOBAL

Evaluation of the safety and efficacy of recombinant soluble thrombomodulin for patients with disseminated intravascular coagulation associated with acute leukemia: multicenter prospective study by the Tohoku Hematology Forum

Yokoyama H.

International Journal of Hematology ( International Journal of Hematology )  105 ( 5 ) 606 - 613   2017年05月

DOI

Drug interaction between tacrolimus and nilotinib in a patient with chronic myeloid leukemia after renal transplant.

Takashi Onaka, Naoto Takahashi, Masatomo Miura, Akihito Yonezawa

Clinical case reports   5 ( 5 ) 605 - 607   2017年05月

Nilotinib, a BCR-ABL tyrosine kinase inhibitor, is a known inhibitor of CYP3A4 and could increase the concentration of drugs metabolized by CYP3A4. An immunosuppressive drug for nilotinib-treated patients following transplant should be administered with careful pharmacokinetic monitoring because of its interaction with nilotinib.

DOI PubMed

Hypoxia-inducible microRNA-210 regulates the DIMT1-IRF4 oncogenic axis in multiple myeloma

Sho Ikeda, Akihiro Kitadate, Fumito Abe, Hirobumi Saitoh, Yoshihiro Michishita, Yoshiaki Hatano, Yoshinari Kawabata, Atsushi Kitabayashi, Kazuaki Teshima, Masaaki Kume, Naoto Takahashi, Hiroyuki Tagawa

Cancer Science ( Blackwell Publishing Ltd )  108 ( 4 ) 641 - 652   2017年04月

Multiple myeloma (MM) is characterized by the accumulation of a population of malignant plasma cells within the bone marrow and its microenvironment. A hypoxic niche is located within the microenvironment, which causes myeloma cells to become quiescent, anti-apoptotic, glycolytic, and immature. Cell heterogeneity may be related to distinct gene expression profiles under hypoxic and normoxic conditions. During hypoxia, myeloma cells acquire these phenotypes by downregulating interferon regulatory factor 4 (IRF4), an essential transcription factor in myeloma oncogenesis. To identify essential microRNAs and their targets regulated under hypoxic conditions, we undertook microRNA and cDNA microarray analyses using hypoxia-exposed primary MM samples and myeloma cell lines. Under hypoxia, only miR-210 was highly upregulated and was accompanied by direct downregulation of an 18S rRNA base methyltransferase, DIMT1. This inverse expression correlation was validated by quantitative RT-PCR for primary MM samples. We further determined that DIMT1 has an oncogenic potential as its knockdown reduced tumorigenicity of myeloma cells through regulation of IRF4 expression. Notably, by analyzing gene expression omnibus datasets in the National Center for Biotechnology Information database, we found that DIMT1 expression increased gradually with MM progression. In summary, by screening for targets of hypoxia-inducible microRNA-210, we identified DIMT1 as a novel diagnostic marker and therapeutic target for all molecular subtypes of MM.

DOI PubMed

Long-term prognosis of AL and AA renal amyloidosis: a Japanese single-center experience

Ozawa M.

Clinical and Experimental Nephrology ( Clinical and Experimental Nephrology )  21 ( 2 ) 212 - 227   2017年04月

Few studies have been conducted on the long-term prognosis of patients with amyloid light chain (AL) and amyloid A (AA) renal amyloidosis in the same cohort.
We retrospectively examined 68 patients with biopsy-proven renal amyloidosis (38 AL and 30 AA). Clinicopathological findings at the diagnosis and follow-up data were evaluated in each patient. We analyzed the relationship between clinicopathological parameters and survival data.
Significant differences were observed in several clinicopathological features, such as proteinuria levels, between the AL and AA groups. Among all patients, 84.2 % of the AL group and 93.3 % of the AA group received treatments for the underlying diseases of amyloidosis. During the follow-up period (median 18 months in AL and 61 months in AA), 36.8 % of the AL group and 36.7 % of the AA group developed end-stage renal failure requiring dialysis, while 71.1 % of the AL group and 56.7 % of the AA group died. Patient and renal survivals were significantly longer in the AA group than in the AL group. eGFR of &gt; 60 mL/min/1.73 m(2) at biopsy and an early histological stage of glomerular amyloid deposition were identified as low-risk factors. A multivariate analysis showed that cardiac amyloidosis and steroid therapy significantly influenced patient and renal survivals.
Our results showed that heart involvement was the major predictor of poor outcomes in renal amyloidosis, and that the prognosis of AA renal amyloidosis was markedly better than that in previously reported cohorts. Therapeutic advances in inflammatory diseases are expected to improve the prognosis of AA amyloidosis.

DOI

リツキシマブ治療を行った成人難治性ネフローゼ症候群7症例の検討

今泉 ちひろ, 加賀 一, 齋藤 雅也, 奈良 瑞穂, 富樫 賢, 小松田 敦, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  59 ( 3 ) 350 - 350   2017年04月

半月体形成糸球体を伴う膜性腎症の臨床病理学的検討

齋藤 雅也, 小松田 敦, 佐藤 隆太, 齋藤 綾乃, 阿部 史人, 加賀 一, 澤村 昌人, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  59 ( 3 ) 351 - 351   2017年04月

当科における特発性膜性腎症患者のHLA DQA1 sequence variants

加賀 一, 森 健介, 阿部 史人, 齋藤 綾乃, 齋藤 雅也, 奈良 瑞穂, 面川 歩, 奥山 慎, 小松田 敦, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  59 ( 3 ) 237 - 237   2017年04月

当科開発ELISAとEuroimmune社ELISAによる当施設での特発性膜性腎症患者の抗phospholipase A2 receptor抗体の比較検討

加賀 一, 阿部 史人, 齋藤 綾乃, 齋藤 雅也, 山本 聡, 横田 伸一, 涌井 秀樹, 小松田 敦, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  59 ( 3 ) 268 - 268   2017年04月

糖尿病性腎症患者の末梢血単核球におけるToll-like receptor(TLR)2、4 mRNA発現と臨床組織学的検討

齋藤 綾乃, 加賀 一, 齋藤 雅也, 奈良 瑞穂, 小松田 敦, 涌井 秀樹, 高橋 直人

日本腎臓学会誌 ( (一社)日本腎臓学会 )  59 ( 3 ) 292 - 292   2017年04月

移植非適応未治療多発性骨髄腫患者に対するLd療法およびレナリドミドの至適血漿中濃度の検討

小林 敬宏, 三浦 昌朋, 新岡 丈典, 鐙屋 舞子, 大八木 秀明, 篠原 良徳, 茂木 睦仁, 黒木 淳, 西成 民夫, 川端 良成, 北林 淳, 道下 吉広, 池田 翔, 志田 青慈, 吉岡 智子, 高橋 直人

International Journal of Myeloma ( 日本骨髄腫学会 )  7 ( 1 ) 71 - 71   2017年04月

維持透析併用で自家移植を行い透析離脱できた多発性骨髄腫

荒井 岳史, 池田 翔, 新井 郷史, 今泉 ちひろ, 山下 鷹也, 北舘 明宏, 小林 五十鈴, 小林 敬宏, 奈良 美保, 郭 永梅, 鵜生川 久美, 渡部 敦, 藤島 直仁, 藤島 眞澄, 吉岡 智子, 亀岡 吉弘, 田川 博之, 高橋 直人

臨床血液 ( (一社)日本血液学会-東京事務局 )  58 ( 4 ) 401 - 402   2017年04月

骨髄腫細胞において低酸素で上昇するコーディング・ノンコーディング遺伝子の網羅的探索とその機能解析

池田 翔, 北舘 明宏, 阿部 史人, 小林 敬宏, 高橋 直人, 田川 博之

International Journal of Myeloma ( 日本骨髄腫学会 )  7 ( 1 ) 54 - 54   2017年04月

J-GLOBAL

Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis

Komatsu N.

International Journal of Hematology ( International Journal of Hematology )  105 ( 3 ) 309 - 317   2017年03月

DOI

DISTRIBUTION PATTERN OF GLOMERULAR IGG SUBCLASS DEPOSITS IN MEMBRANOUS NEPHROPATHY PATIENTS WITH CRESCENT FORMATION AND POSITIVE MPO-ANCA

Masaya Saitoh, Atsushi Komatsuda, Yuhta Oyama, Masato Sawamura, Masatoyo Ozawa, Hideki Wakui, Naoto Takahashi

RHEUMATOLOGY ( OXFORD UNIV PRESS )  56   138 - 138   2017年03月

Erratum to: Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis (International Journal of Hematology, (2017), 105, 3, (309-317), 10.1007/s12185-016-2130-z)

Komatsu N.

International Journal of Hematology ( International Journal of Hematology )  105 ( 3 )   2017年03月

DOI

ANCA-ASSOCIATED VASCULITIS COMPLICATING WITH LARGE VESSEL INVOLVEMENT AND HYPERTROPHIC PACHYMENINGITIS: REPORT OF AN AUTOPSY CASE AND REVIEW OF THE LITERATURE

Hajime Kaga, Atsushi Komatsuda, Masaya Saitoh, Mizuho Nara, Ayumi Omokawa, Masaru Togashi, Shin Okuyama, Hideki Wakui, Naoto Takahashi

RHEUMATOLOGY ( OXFORD UNIV PRESS )  56   70 - 70   2017年03月

Evaluation of the safety and efficacy of recombinant soluble thrombomodulin for patients with disseminated intravascular coagulation associated with acute leukemia: multicenter prospective study by the Tohoku Hematology Forum.

Yokoyama H, Takahashi N, Katsuoka Y, Inomata M, Ito T, Meguro K, Kameoka Y, Tsumanuma R, Murai K, Noji H, Ishizawa K, Ito S, Onishi Y, Harigae H, Tohoku Hematology Forum

International Journal of Hematology   105 ( 5 ) 606 - 613   2017年02月

DOI

Clinicopathological characteristics of malignant lymphoma in patients with hepatitis C virus infection in the Tohoku district in Eastern Japan.

Tajima K, Takahashi N, Ishizawa K, Murai K, Akagi T, Noji H, Sasaki O, Wano M, Itoh J, Kato Y, Shichishima T, Harigae H, Ishida Y, Tohoku Hematology Forum

Leuk Lymphoma.   58 ( 6 ) 1509 - 1511   2017年01月

DOI

[Refractory CD20-positive peripheral T-cell lymphoma showing loss of CD20 expression after rituximab therapy and gain of CD20 expression after administration of vorinostat and gemcitabine].

Teshima K, Ohyagi H, Kume M, Takahashi S, Saito M, Takahashi N

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 一般社団法人 日本血液学会 )  58 ( 11 ) 2227 - 2231   2017年

<p>79歳，男性。全身リンパ節腫脹で発症したT細胞受容体β鎖遺伝子再構成陽性，CD20陽性末梢性T細胞性リンパ腫（peripheral T-cell lymphoma, PTCL）, NOSに対してR-CHOP療法6コース施行し部分寛解を得た。2ヶ月後に早期再発を来たし，頸部リンパ節および皮膚の再生検でCD20陰転化を確認した。リンパ節病変はCCR4陽性であった。救援療法のGDP療法は奏効しなかった。皮膚病変に対してvorinostatを投与したが骨髄抑制のため中止，その後さらに皮膚病変は増悪した。増大した頸部リンパ節の生検を再度行ったところ，CD20再発現を認めた。CCR4陽性に対してmogamulizumabを投与したが病勢増悪し，再発から8ヶ月で死亡した。本例はCD20の発現がrituximab，vorinostat，gemcitabine治療の経過中に変化した興味深い症例と考えられる。</p>

DOI PubMed CiNii Research

Effects of denosumab on bone metabolic markers and bone mineral density in patients treated with glucocorticoids

Sawamura M.

Internal Medicine ( Internal Medicine )  56 ( 6 ) 631 - 636   2017年

Objective We performed a prospective study to determine the efficacy and safety of denosumab on bone metabolic indices and bone mineral density (BMD) in 29 patients receiving long-term glucocorticoids (GCs) who had clinical risk factors for fracture. Methods Among these patients, 16 had systemic lupus erythematosus (SLE), 6 RA, 4 other autoimmune diseases, and 3 renal diseases. All patients received donosumab 60 mg at baseline and 6 months. Serum N-terminal cross-linked telopeptide of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) levels were measured as bone metabolic indices. BMD at the lumbar spine (LSBMD) and femoral neck (FNBMD) were measured using dual energy X-ray absorptiometry and expressed as a percentage of the young adult mean (%YAM). Results Denosumab therapy significantly reduced serum NTX and BAP levels from baseline after 12 months (from 19.2 to 13.9 nmol BCE/L
from 11.9 to 9.2 U/L, respectively). In 18 patients treated with bisphosphonates before the start of denosumab therapy, the improvements in the LSBMD and FNBMD values were 1.5%YAM/year and 1.1%YAM/year, respectively. The LSBMD and FNBMD values were both significantly higher 12 months after denosumab therapy (3.5%YAM/year and 3.0%YAM/year, respectively). The LSBMD gain was significantly higher after denosumab therapy than during bisphosphonate therapy. No fractures were observed in any patients during denosumab therapy. Conlusion Denosumab is effective and safe in preventing bone resorption and BMD loss in patients treated with long-term GCs for inflammatory diseases. This is the first study showing a significant increase in not only LSBMD but also FNBMD in GC-induced osteoporosis after denosumab therapy.

DOI PubMed CiNii Research

Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia

Togasaki E.

Blood Cancer Journal ( Blood Cancer Journal )  7 ( 4 ) e559   2017年

Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1-17). Age, hemoglobin concentration and white blood cell counts were correlated with the number of mutations. Patients with mutations &gt;= 6 showed higher rate of achieving major molecular response than thoseo6 (P = 0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6 were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one patient each. ASXL1 was mutated within exon 12 in three cases. Mutated genes were significantly enriched with cell signaling and cell division pathways. Furthermore, DNA copy number analysis showed that 2 of 24 patients had uniparental disomy of chromosome 1p or 3q, which disappeared major molecular response was achieved. These mutations may play significant roles in CML pathogenesis in addition to the strong driver mutation BCR-ABL1.

DOI PubMed

Histone deacetylase inhibitors inhibit metastasis by restoring a tumor suppressive microRNA-150 in advanced cutaneous T-cell lymphoma

Abe F.

Oncotarget ( Oncotarget )  8 ( 5 ) 7572 - 7585   2017年

Tumor suppressive microRNA (miR)-150 inhibits metastasis by combining with the C-C chemokine receptor 6 (CCR6) "seed sequence" mRNA of the 3'-untranslated region (3'-UTR) in advanced cutaneous T-cell lymphoma (CTCL). Because the histone deacetylase inhibitor (HDACI) vorinostat showed excellent outcomes for treating advanced CTCL, HDACIs may reduce the metastasis of CTCL by targeting miR-150 and/ or CCR6. To examine whether these candidate molecules are essential HDACI targets in advanced CTCL, we used the My-La, HH, and HUT78 CTCL cell lines for functional analysis because we previously demonstrated that their xenografts in NOD/Shi-scid IL-2γnul mice (CTCL mice) induced multiple metastases. We found that pan- HDACIs (vorinostat and panobinostat) inhibited the migration of CTCL cells and downregulated CCR6. The miRNA microarray analysis against CTCL cell lines demonstrated that these pan-HDACIs commonly upregulated 161 miRNAs, including 34 known tumor suppressive miRNAs such as miR-150. Although 35 miRNAs possessing the CCR6 "seed sequence" were included in these 161 miRNAs, miR-150 and miR-185-5p were downregulated in CTCL cells compared to in normal CD4+ T-cells. The transduction of 12 candidate miRNAs against CTCL cells revealed that miR-150 most efficiently inhibited their migration capabilities and downregulated CCR6. Quantitative reverse transcriptase-polymerase chain reaction demonstrated that miR-150 was downregulated in advanced but not early CTCL primary cases. Finally, we injected miR-150 or siCCR6 into CTCL mice and found that mouse survival was significantly prolonged. These results indicate that miR-150 and its target, CCR6, are essential therapeutic targets of pan-HDACIs in advanced CTCL with metastatic potential.

DOI PubMed

Successful management of splenomegaly with ruxolitinib prior to allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia transformed from post-polycythemia vera myelofibrosis.

Masumi Fujishima, Naohito Fujishima, Akihiro Kitadate, Yongmei Guo, Atsushi Watanabe, Kumi Ubukawa, Miho Nara, Tomoko Yoshioka, Yoshihiro Kameoka, Naoto Takahashi

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 一般社団法人 日本血液学会 )  58 ( 7 ) 743 - 748   2017年

A 64-year-old woman was admitted to our hospital to undergo allogeneic stem cell transplantation. She was diagnosed with polycythemia vera with a JAK2 V617F mutation 7 years ago. She was administered ruxolitinib for splenomegaly two years prior to admission but this was discontinued because of progressive pancytopenia. One months after cessation of ruxolitinib, she developed acute myeloid leukemia transformed from post-polycythemia vera myelofibrosis. Although she achieved complete remission after induction therapy, 8-finger-breadth splenomegaly remained below the left costal margin. Ruxolitinib was re-administered following two courses of consolidation therapy. She underwent unrelated peripheral blood stem cell transplantation. Ruxolitinib was administered until the day before transplantation, and the spleen was palpated in 4-finger breadth below costal arc. Neutrophil engraftment was achieved 13 days after transplantation. In allogeneic stem cell transplantation, splenomegaly is one of the risk factors for engraftment failure and/or therapy-related mortality. Hence, a smaller spleen size can theoretically improve the outcome after transplantation. The administration of ruxolitinib prior to transplantation may have contributed to engraftment with a non-invasive reduction in the size of the spleen.

DOI PubMed CiNii Research

TAFRO Syndrome with Bilateral Adrenal Hemorrhage

Ito F, Kameoka Y, Nara M, Ubukawa K, Fujishima M, Yoshioka T, Fujishima N, Takahashi N

Nihon Naika Gakkai Zasshi. ( 日本内科学会 )  106 ( 2 ) 288 - 294   2017年

CiNii Research

Two cases of thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome with high serum procalcitonin levels, including the first case complicated with adrenal hemorrhaging

Nara M.

Internal Medicine ( Internal Medicine )  56 ( 10 ) 1247 - 1252   2017年

Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/Renal failure, and Organomegaly (TAFRO) syndrome is a recently described systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly. It has an acute or subacute onset of unknown etiology, although some pathological features resemble those of multicentric Castleman disease. We here report two cases of TAFRO syndrome. The symptoms and pathological findings in these cases met the 2015 diagnostic criteria. Our cases showed high serum procalcitonin levels, suggesting bacterial infection as an onset trigger. In addition, Case 1 is the first case complicated with adrenal hemorrhaging. Case 2 is the second case of tocilizumab-resistant TAFRO syndrome successfully treated with rituximab.

DOI CiNii Research

両側副腎出血を合併したTAFRO症候群

伊藤 史子, 亀岡 吉弘, 奈良 美保, 鵜生川 久美, 藤島 眞澄, 吉岡 智子, 藤島 直仁, 高橋 直人

日本内科学会雑誌 ( 一般社団法人 日本内科学会 )  106 ( 2 ) 288 - 294   2017年

<p>48歳，男性．発熱，全身性浮腫とリンパ節腫脹で発症し，炎症反応高値，副腎出血，血小板減少，骨髄線維化を認めた．副腎出血による副腎不全を合併した悪性リンパ腫を疑ったが，リンパ節生検にてCastleman病の病理所見と一致し，多彩な臨床症状と検査所見を総合的に判断し，TAFRO症候群と診断した．Prednisolone（PSL）により症状の改善がみられた．頻度は稀だが，本症例のような多彩な臨床症状と特徴的な検査所見を示す場合，TAFRO症候群を念頭に置く必要がある．</p>

DOI CiNii Research