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宮田 吉晴大学院医学研究科 医科学専攻准教授
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■ 論文- Springer Science and Business Media LLC, 2024年11月, International Journal of Clinical Oncology, 英語[査読有り]研究論文（学術雑誌）
- (一社)日本血栓止血学会, 2024年05月, 日本血栓止血学会誌, 35(2) (2), 336 - 336, 日本語進行・再発・転移の固形腫瘍における血栓塞栓症と出血リスク PROVE-emboli試験post-hoc解析
- Japan Society of Mechanical Engineers, 2024年, Journal of Advanced Mechanical Design, Systems, and Manufacturing, 18(4) (4), JAMDSM0037 - JAMDSM0037[査読有り]研究論文（学術雑誌）
- BACKGROUND: We previously demonstrated that CD34 + cell transplantation in animals healed intractable fractures via osteogenesis and vasculogenesis; we also demonstrated the safety and efficacy of this cell therapy in an earlier phase I/II clinical trial conducted on seven patients with fracture nonunion. Herein, we present the results of a phase III clinical trial conducted to confirm the results of the previous phase studies using a larger cohort of patients. METHODS: CD34 + cells were mobilized via administration of granulocyte colony-stimulating factor, harvested using leukapheresis, and isolated using magnetic cell sorting. Autologous CD34 + cells were transplanted in 15 patients with tibia nonunion and 10 patients with femur nonunion, who were followed up for 52 weeks post transplantation. The main outcome was a reduction in time to heal the tibia in nonunion patients compared with that in historical control patients. We calculated the required number of patients as 15 based on the results of the phase I/II study. An independent data monitoring committee performed the radiographic assessments. Adverse events and medical device failures were recorded. RESULTS: All fractures healed during the study period. The time to radiological fracture healing was 2.8 times shorter in patients with CD34 + cell transplantation than in the historical control group (hazard ratio: 2.81 and 95% confidence interval 1.16-6.85); moreover, no safety concerns were observed. CONCLUSIONS: Our findings strongly suggest that autologous CD34 + cell transplantation is a novel treatment option for fracture nonunion. TRIAL REGISTRATION: UMIN-CTR, UMIN000022814. Registered on 22 June 2016.2023年10月, BMC medicine, 21(1) (1), 386 - 386, 英語, 国際誌研究論文（学術雑誌）
- Abstract Coronavirus disease (COVID-19) often causes persistent symptoms long after infection, referred to as “long COVID” or post-acute COVID-19 syndrome (PACS). This phenomenon has been studied primarily concerning B-cell immunity, while the involvement of T-cell immunity is still unclear. This retrospective study aimed to examine the relationship among the number of symptoms, cytokine levels, and the Enzyme-linked immunosorbent spot (ELISPOT) assay data in patients with COVID-19. To examine inflammatory conditions, plasma interleukin (IL)-6, IL-10, IL-18, chemokine ligand 9 (CXCL9), chemokine ligand 3 (CCL3), and vascular endothelial growth factor (VEGF) levels were analyzed using plasma obtained from COVID-19 recovery patients and healthy controls (HC). These levels were significantly higher in the COVID-19 group than those in the HC group. ELISPOT assays were performed to investigate the correlation between COVID-19 persistent symptoms and T-cell immunity. Cluster analysis of ELISPOT categorized COVID-19 recovery patients in the ELISPOT-high and -low groups, based on the values of S1, S2, and N. The number of persistent symptoms was significantly higher in the ELISPOT-low group than those in the ELISPOT-high group. Thus, T cell immunity is critical for the rapid elimination of COVID-19 persistent symptoms, and its measurement immediately after COVID-19 recovery might predict long-term COVID-19 or PACS.Springer Science and Business Media LLC, 2023年07月, Scientific Reports, 13(1) (1), 国際誌[査読有り]研究論文（学術雑誌）
- Abstract Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis for SOS can improve clinical outcomes significantly. Here, we performed a retrospective study to investigate the Cairo diagnostic criteria, in which SOS was defined as the development of two or more in seven events, including transfusion‐refractory thrombocytopenia. Among 154 cases of allogeneic HSCT, 10 cases of SOS using the European Society for Blood and Marrow Transplantation criteria (EBMT16) as the reference standard were identified. The original Cairo criteria could diagnose SOS 5 days earlier than any other established criteria, with some false‐positive results (sensitivity = 100.0%; specificity = 72.2%). When the cutoff was set to three events for the Cairo criteria, the diagnosis of SOS could be made 3 days earlier than that using the EBMT16 criteria, with comparable precision (specificity = 86.1%). The accuracy of the Cairo criteria improved further when the cutoff point was set to four (specificity = 93.8%). The fulfillment of the Cairo criteria was associated with high mortality. Based on our results, the Cairo criteria were also considered clinically useful, especially at three or four cutoff points. Further studies are required to validate and refine the criteria.Wiley, 2023年06月, eJHaem[査読有り]研究論文（学術雑誌）
- (一社)日本血栓止血学会, 2023年05月, 日本血栓止血学会誌, 34(2) (2), 195 - 195, 日本語進行・再発・転移の未治療固形がん患者における静脈血栓塞栓症の前向き観察研究の統合解析
- (一社)日本内科学会, 2023年02月, 日本内科学会雑誌, 112(臨増) (臨増), 163 - 163, 日本語がん関連静脈血栓塞栓症に対するアピキサバン療法の出血リスク予測 多施設共同第2相臨床試験副次的解析
- In acute myeloid leukemia (AML), the heterogeneity of genetic and epigenetic characteristics makes treatment difficult. The prognosis for AML is therefore poor, and there is an urgent need for new treatments for this condition. Gemtuzumab ozogamicin (GO), the first antibody-drug conjugate (ADC), targets the CD33 antigen expressed in over 90% of AML cases. GO therefore has the potential to counter the heterogeneity of AML patients. However, a major clinical problem is that drug resistance to GO diminishes its effect over time. Here, we report that the inhibition of glycogen synthase kinase 3 (GSK3) alone overcomes several forms of GO resistance at concentrations without antileukemic effects. The GSK3 inhibitors tested significantly enhanced the cytotoxic effect of GO in AML cell lines. We elucidated four mechanisms of enhancement: (1) increased expression of CD33, the target antigen of GO; (2) activation of a lysosomal function essential for hydrolysis of the GO linker; (3) reduced expression of MDR1 that eliminates calicheamicin, the payload of GO; and (4) reduced expression of the anti-apoptotic factor Bcl-2. A similar combination effect was observed against patient-derived primary AML cells. Combining GO with GSK3 inhibitors may be efficacious in treating heterogeneous AML.2023年02月, EJHaem, 4(1) (1), 153 - 164, 英語, 国際誌研究論文（学術雑誌）
- We previously reported that a second dose of BNT162b2 was safe and effective for allogeneic hematopoietic stem cell transplantation (HSCT) patients. Here, we investigated the safety and efficacy of a third dose of COVID-19 mRNA vaccine in allogeneic HSCT patients. Antibody titers against the S1 spike protein were measured using the QuaResearch COVID-19 Human IgM IgG ELISA kit. The previous study included 25 allogeneic HSCT patients who received two doses of BNT162b2. Following the exclusion of three patients because of the development of COVID-19 (n = 2) and loss to follow-up (n = 1), the study evaluated 22 allogeneic HSCT patients who received a third dose of COVID-19 mRNA vaccine (BNT162b2 [n = 15] and mRNA-1273 [n = 7]). Median age at the time of the first vaccination was 56 (range, 23-71) years. Five patients were receiving immunosuppressants at the third vaccination, namely calcineurin inhibitors (CI) alone (n = 1), steroids alone (n = 2), or CI combined with steroids (n = 2). Twenty-one patients (95%) seroconverted after the third dose. None of our patients had serious adverse events, new-onset graft-versus-host disease (GVHD), or GVHD exacerbation after vaccination. A third dose of the BNT162b2 and mRNA-1273 COVID-19 vaccines was safe and effective for allogeneic HSCT patients.2022年10月, Vaccines, 10(11) (11), 英語, 国際誌研究論文（学術雑誌）
- Cytomegalovirus (CMV) oophoritis is an extremely rare and fatal condition. We encountered a 63-year-old woman with CMV oophoritis who had been treated for Burkitt's lymphoma. Positron emission tomography/computed tomography performed after chemotherapy showed a high 18F-fluoro-2deoxy-D-glucose uptake in both ovaries, which required distinguishing relapse. CMV oophoritis was diagnosed on histology following bilateral salpingo-oophorectomy. Although the patient later developed recurrent episodes of CMV antigenemia, after which complications of CMV retinitis appeared, and she ultimately died of CMV meningitis, surgical resection with antiviral medication resolved her abdominal symptoms and cleared CMV antigenemia for several weeks. It is therefore worth considering surgical resection in combination with antiviral drugs as a treatment option.2022年10月, Internal medicine (Tokyo, Japan), 英語, 国内誌研究論文（学術雑誌）
- OBJECTIVES: Oral corticosteroids reduce the antibody titer of the BNT162b2 mRNA vaccine against SARS-CoV-2. To date, the effect of inhaled corticosteroids on antibody titers is unknown. STUDY DESIGN: The design of this study is retrospective study. METHODS: We analyzed the relationship between the clinical features and total antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in 320 subjects who had never been infected with Coronavirus disease 2019 (COVID-19) and were vaccinated the second time with the BNT162b2 mRNA vaccine between October 1 to December 28, 2021. RESULTS: Of the 320 subjects, 205 were treated with inhaled corticosteroids. The median antibody titer of patients treated with inhaled corticosteroids was 572 U/mL, which was significantly higher than that of patients treated without inhaled corticosteroids (454U/mL, P = 0.00258). The median antibody titers of smokers, men, and patients aged 65 years and over, were 315.5 U/mL, 385 U/mL, and 425.5 U/mL, respectively. These results are significantly lower than those of patients who never smoked, women, and patients aged less than 64 years (582 U/mL [P < 0.0001], 682.5 U/mL [P < 0.0001], and 717 U/mL [P < 0.0001], respectively). The multivariate analysis revealed that females and age were independent antibody titer-reducing factors (P = 0.0001 and P < 0.0001, respectively). CONCLUSIONS: The use of inhaled corticosteroids did not reduce the antibody titer against SARS-CoV-2 spike protein. Clinicians should continue treatment with inhaled corticosteroids if indicated.2022年08月, Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology, 18(1) (1), 78 - 78, 英語, 国際誌研究論文（学術雑誌）
- (一社)日本医療検査科学会, 2022年08月, 医療検査と自動化, 47(4) (4), 455 - 455, 日本語
- Anti-CD20 antibodies react with CD20 expressed not only on malignant B cells, but also on normal B cells. It has been reported that patients treated with anti-CD20 antibodies had an insufficient response to two-dose mRNA SARS-CoV-2 vaccination. To investigate the efficacy of a third dose in these patients, we investigated serum IgG antibody titers for the S1 protein after a third vaccination in 22 patients treated with the anti-CD20 antibody who failed two-dose vaccination. Results showed that overall, 50% of patients seroconverted. Although no patient who received the third dose within 1 year of the last anti-CD20 antibody administration showed an increase in S1 antibody titer, 69% of patients who received the third dose more than 1 year after the last anti-CD20 antibody administration seroconverted. Our data show that a third dose of vaccination is effective in improving the seroconversion rate in patients treated with the anti-CD20 antibody who failed standard two-dose vaccination.2022年06月, Vaccines, 10(6) (6), 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Recent pivotal phase III trials involving direct oral anticoagulant (DOAC) versus low molecular weight heparin have demonstrated the utility of DOACs in Western patients with cancer-associated venous thromboembolism (VTE). However, these trials did not include Japanese patients. This phase II trial evaluated the safety and efficacy of apixaban in Japanese patients with cancer-associated VTE (UMIN000028447). METHOD AND RESULTS: Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. The primary endpoint was the incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. The study was terminated due to safety concerns after enrolling 27 patients. Median age was 71 years; median body weight was 51.3 kg; and major primary tumor sites were the gastrointestinal tract (26%) and lung (19%). During the median follow-up period of 5.4 months, major or CRNM bleeding occurred in in 26% of patients (major, n = 5; CRNM, n = 2; 95% confidence interval, 11-46%). No recurrent VTE or VTE-related death occurred. Estimated overall survival at 6 months was 68%. CONCLUSION: This study demonstrated the excessive bleeding risk of apixaban at the standard dose in Japanese patients with cancer-associated VTE.2022年04月, International journal of hematology, 115(4) (4), 499 - 507, 英語, 国内誌研究論文（学術雑誌）
- Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of the COVID-19 vaccine in HSCT patients remain to be investigated. We prospectively evaluated the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine (Pfizer BioNTech) in 25 Japanese allogeneic HSCT patients in comparison with 19 healthy volunteers. While anti-S1 antibody titers in almost all healthy volunteers after the second dose were higher than the cut-off value reported previously, levels in HSCT patients after the second dose were diverse. Nineteen patients (76%) had seroconversion of anti-S1 IgG. The median optical density of antibody levels in HSCT patients with low IgG levels (<600 mg/dL), steroid treatment, or low lymphocytes (<1000/μL) was significantly lower than that in the other HSCT patients. There were no serious adverse events (>Grade 3) and no new development or exacerbation of graft-versus-host disease after vaccination. We concluded that the BNT162b2 mRNA vaccine is safe and effective in Japanese allogeneic HSCT patients.2022年01月, Vaccines, 10(2) (2), 英語, 国際誌研究論文（学術雑誌）
- We investigated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. Although T-cell-mediated immune responses were detected even in patients receiving R-CHOP treatment, the S1 antibody titer following BNT162b2 vaccination remained only marginally increased for more than 3 years after the final dose of anti-CD20 antibody. We found no relationship between the percent of B-cells and S1 antibody titer. The duration of this suppression was much longer than we anticipated. Further protection and treatment strategies against COVID-19 for these patients are warranted.2022年01月, International journal of hematology, 115(1) (1), 7 - 10, 英語, 国内誌研究論文（学術雑誌）
- BACKGROUND: The incidence of cancer-associated venous thromboembolism (CA-VTE) in Japan has not been fully investigated. METHODS AND RESULTS: Clinicopathological information from patients with solid malignancies who first visited our department between November 2011 and March 2018 were retrospectively reviewed from medical records. The primary outcome was incidence of CA-VTE, defined as deep-vein thrombosis (DVT) and/or pulmonary embolism (PE). On median follow-up of 187 days, 91 of 2735 patients (3.3%) developed CA-VTE during their clinical course, giving an incidence rate of 40.7 per 1000 person-years. Of the 91 patients, 75 (82%) were diagnosed with DVT alone, 6 (7%) with PE alone, and 10 (11%) with both DVT and PE. CA-VTE was most frequent in non-small cell lung cancer (10.8%), followed by cancer of unknown origin (5.8%). Forty-four patients (48%) had one or more symptoms at the initial diagnosis of VTE. Five patients (6%) had a normal D-dimer level (≤ 1.0 µg/mL); of these, 2 were asymptomatic. CONCLUSIONS: In this retrospective study, the incidence of CA-VTE in Japanese patients with cancer was equivalent to that in Western populations. Approximately half of CA-VTE patients were asymptomatic and 6% had normal D-dimer levels, indicating the need for closer attention to occult CA-VTE.2021年09月, International journal of hematology, 114(3) (3), 319 - 324, 英語, 国内誌研究論文（学術雑誌）
- The t(1;11)(p32;q23) translocation is a rare but recurrent cytogenetic aberration in acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL). This translocation was initially shown to form a fusion gene between KMT2A exon 8 at 11q23 and EPS15 exon 2 at 1p32 in AML. Activating mutations of FLT3 are frequently found in AML but are very rare in ALL. Here, we describe a 75-year-old woman who was diagnosed with B-ALL since her bone marrow was made up of 98.2% lymphoblasts. These blasts were positive for CD19, CD22, CD79a, CD13, and CD33 but negative for CD10 and myeloperoxidase. The karyotype by G-banding and spectral karyotyping was 46,XX,t(1;11)(p32;q23). Expression of KMT2A/EPS15 and reciprocal EPS15/KMT2A fusion transcripts were shown: KMT2A exon 8 was in-frame fused to EPS15 exon 12, indicating that this fusion transcript was a novel type. Considering three reported B-ALL cases, EPS15 breakpoints were markedly different between AML (exon 2) and B-ALL (exons 10-12). Furthermore, an uncommon type of FLT3 mutation in the juxtamembrane domain was detected: in-frame 4-bp deletion and 10-bp insertion. Accordingly, our results indicate that the novel type of KMT2A/EPS15 fusion transcript and FLT3 mutation may cooperate in the pathogenesis of adult B-ALL as class II and class I mutations, respectively.2021年06月, Cancer genetics, 254-255, 92 - 97, 英語, 国際誌研究論文（学術雑誌）
- Gemtuzumab ozogamicin (GO), an anti-CD33 antibody linked to calicheamicin via an acid-labile linker, is the first antibody-drug conjugate (ADC). The acidic environment inside lysosomes of target cells is an important intracellular determinant of the cytocidal action of GO, as the linker is hydrolyzed under acidic conditions. However, lysosomal activity in acute myeloid leukemia (AML) blasts in GO therapy has been insufficiently evaluated. It has been suggested that lysosome activity is suppressed in AML due to hyperactivation of the phosphoinositide 3-kinase/Akt pathway. We therefore hypothesized that agents which activate lysosomal function would potentiate the cytotoxicity of GO. Here, we found that a clinically useful mTORC1/2 dual inhibitor, AZD2014, reduced pH in the acidic organelles, including lysosomes, as shown by increased LysoTracker fluorescent intensity, and synergistically enhanced the cytotoxic effect of GO in primary leukemia cells. GO-induced cytotoxicity appeared to be enhanced with the increase in lysosomal activity by AZD2014. These results indicate that AZD2014 activated lysosomal function in primary leukemia cells, which in turn enhanced the cytotoxicity of GO. Enhancement of lysosomal activity may represent a new therapeutic strategy in the treatment of GO and other ADCs, particularly in cases with low lysosomal activity.2019年10月, International journal of hematology, 110(4) (4), 490 - 499, 英語, 国内誌研究論文（学術雑誌）
- A 45-year-old woman was diagnosed with hepatosplenic T-cell lymphoma (HSTCL), a rare subtype of peripheral T-cell lymphoma. She received different types of chemotherapy, but disease progression was observed. To reduce the tumor burden before an unrelated bone marrow transplantation, combination chemotherapy consisting of the gemcitabine, carboplatin, and dexamethasone (GCD) was administered as bridging therapy, resulting in a reduction in the number of lymphoma cells. We were then able to perform bone marrow transplantation. Although she experienced some adverse events, she successfully achieved long-term remission. We herein report a successful case of HSTCL treated with unrelated stem cell transplantation following the GCD regimen as bridging chemotherapy.2019年03月, Internal medicine (Tokyo, Japan), 58(5) (5), 707 - 712, 英語, 国内誌研究論文（学術雑誌）
- BACKGROUND: Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. METHODS AND RESULTS: We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. CONCLUSIONS: Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.2019年02月, Transplant infectious disease : an official journal of the Transplantation Society, 21(1) (1), e13024, 英語, 国際誌研究論文（学術雑誌）
- Scopulariopsis alboflavescens is a soil saprophyte that is widely distributed in nature. Recently, there have been increasing number of reports of invasive infections with Scopulariopsis species in immunocompromised patients. In this report, we described an adult woman with acute myeloid leukemia and who developed S. alboflavescens pneumonia. Liposomal amphotericin B and voriconazole combination therapy was unsuccessful and the patient died because of pneumonia. Scopulariopsis is highly resistant to available antifungal agents and almost invariably fatal. This case report should alert clinicians to the importance of listing Scopulariopsis as a pathogenic fungus in immunocompromised patients.2018年12月, International journal of hematology, 108(6) (6), 658 - 664, 英語, 国内誌研究論文（学術雑誌）
- Gemtuzumab ozogamicin (GO), the first antibody-drug conjugate (ADC), has attracted the interest of hematologists because more than 90% of acute myeloid leukemia (AML) blasts express its target, CD33. Although GO and subsequently developed ADCs depend on lysosomes for activation, lysosome number and activity in tumor cells has not been well elucidated. In this study, we investigated whether an mTORC1/2 kinase inhibitor, PP242, which was reported to activate lysosomal function, potentiates the cytotoxicity of GO in AML cells. Eight AML cell lines (U937, THP-1, SKM-1, SKK-1, SKNO-1, HL-60, MARIMO and KO52) were treated with GO and PP242. The cytotoxic effect of GO was enhanced by concurrent treatment with a non-cytotoxic concentration (500 nM) of PP242 in most cell lines, except MARIMO and KO52 cells. We then used LysoTracker to label acidic lysosomes in U937, THP-1, SKM-1, MARIMO and KO52 cells. LysoTracker fluorescence was dramatically increased by treatment with PP242 in U937, THP-1 and SKM-1 cells, and the intensified fluorescence was retained with PP242 + GO. In contrast, PP242 did not induce a significant increase in fluorescence in MARIMO cells, consistent with the lack of combinatory cytotoxicity. LysoTracker fluorescence was also increased by PP242 in KO52 cells, which have been reported to strongly express multidrug resistance (MDR). Further, PP242 suppressed GO-induced Chk1 activation and G2/M cell cycle arrest, which in turn triggered cell cycle promotion and cell death. These results indicate that inhibition of mTORC1/2 kinase by PP242 enhanced the cytotoxicity of GO by increasing lysosomal compartments and promoting the cell cycle via suppression of GO-induced Chk1 activation. This combination may represent an attractive new therapeutic strategy for the treatment of leukemia.2018年11月, Leukemia research, 74, 68 - 74, 英語, 国際誌研究論文（学術雑誌）
- Immune reconstitution affects clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT), and it has been suggested that lymphocyte recovery affects survival after HSCT. However, few studies have examined lymphocyte recovery in Asian patients who received mycophenolate mofetil (MMF) prophylaxis for graft-versus-host disease. We retrospectively evaluated early lymphocyte recovery after HSCT among Japanese adults who received MMF prophylaxis. Patients were divided into two groups according to their median absolute lymphocyte count (ALC) on day 28 after HSCT as follows: the "low ALC group" (≤ 0.22 × 109 cells/L) and the "high ALC group" (> 0.22 × 109 cells/L). With a median follow-up of 317 days, the high ALC group showed significantly better overall survival than the low ALC group (at 1 year: 62 vs. 46%, P = 0.02). The high ALC group also tended to have better non-relapse mortality than the low ALC group (at 1 year: 13 vs. 23%, P = 0.08). There was no significant difference in relapse rate between the high and low ALC groups (at 1 year: 29 vs. 35%, P = 0.2). We conclude that among Japanese patients who received MMF prophylaxis, ALC on day 28 after HSCT was effective in predicting overall survival and non-relapse mortality.2018年07月, International journal of hematology, 108(1) (1), 58 - 65, 英語, 国内誌研究論文（学術雑誌）
- PURPOSE: Mycophenolate mofetil (MMF) is increasingly used among Japanese patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Because pharmacokinetic data for MMF in the Asian population are limited, we conducted this investigation. METHODS: Intravenous MMF (1000 mg/dose) was administered to 10 patients along with cyclosporine or tacrolimus for 10 days after allo-SCT; it was administered every 8 h in peripheral blood stem cell- and bone marrow-transplanted patients, and every 12 h in cord blood-transplanted patients. MMF was administered orally at the same dose from day 11. Plasma concentrations of mycophenolic acid (MPA) were measured by high-performance liquid chromatography. RESULTS: The MPA AUC0 - tau was 31.9 ± 3.4, 26.2 ± 2.4, and 21.0 ± 2.2 µg*h/mL, the mean Ctrough was 0.25, 0.35, and 0.37 µg/mL, and the Cmax was 10.8, 9.2, and 5.5 µg/mL on days 2, 9, and 16, respectively. The AUC0 - tau and Cmax were significantly higher after intravenous MMF dosing than after oral MMF dosing. All patients exhibited successful neutrophil engraftments in a median time of 18 days. Grade II acute graft-versus-host disease (GvHD) of the skin was observed in two patients, and one patient developed limited chronic GvHD. Individual cases of transient and curable grade III oral mucositis and diarrhea were observed; however, MMF was not discontinued. No other severe complications or infections were observed. CONCLUSIONS: Intravenously administered MMF was safe and possibly effective in achieving higher MPA plasma concentrations for GvHD prophylaxis after allo-SCT in Japanese patients.2018年05月, Cancer chemotherapy and pharmacology, 81(5) (5), 839 - 846, 英語, 国際誌研究論文（学術雑誌）
- Lymph node infarction is very rare, and is frequently associated with neoplasms, such as malignant lymphoma and non-neoplastic disease, or interventions such as fine-needle aspiration (FNA). A 76-year-old-man presented with cervical lymph node swelling. Although FNA was performed, the findings were insufficient for a definitive diagnosis. Consequently, surgical biopsy of the cervical lymph node was performed, which revealed total infarction; a diagnosis of classical Hodgkin lymphoma was made later. Both lymphoma itself and FNA may cause total lymph node infarction, which makes diagnosis confusing. Therefore, it is important to repeat the biopsy rather than repeat FNA to correctly diagnose malignant lymphoma, including Hodgkin lymphoma.2018年03月, Journal of clinical and experimental hematopathology : JCEH, 58(1) (1), 24 - 26, 英語, 国内誌研究論文（学術雑誌）
- Aberrant activation of the Hedgehog (Hh) signaling pathway is involved in the maintenance of leukemic stem cell (LSCs) populations. PF-0444913 (PF-913) is a novel inhibitor that selectively targets Smoothened (SMO), which regulates the Hh pathway. Treatment with PF-913 has shown promising results in an early phase study of acute myeloid leukemia (AML). However, a detailed mode of action for PF-913 and relevant biomarkers remain to be elucidated. In this study, we examined bone marrow samples derived from AML patients under PF-913 monotherapy. Gene set enrichment analysis (GSEA) revealed that PF-913 treatment affected the self-renewal signature and cell-cycle regulation associated with LSC-like properties. We then focused on the expression of a pluripotency factor, NANOG, because previous reports showed that a downstream effector in the Hh pathway, GLI, directly binds to the NANOG promoter and that the GLI-NANOG axis promotes stemness and growth in several cancers. In this study, we found that a change in NANOG transcripts was closely associated with GLI-target genes and NANOG transcripts can be a responsive biomarker during PF-913 therapy. Additionally, the treatment of AML with PF-913 holds promise, possibly through inducing quiescent leukemia stem cells toward cell cycling.2017年02月, International journal of molecular sciences, 18(3) (3), 英語, 国際誌研究論文（学術雑誌）
- A prospective study of the antiemetic effect of palonosetron in malignant lymphoma patients treated with the CHOP regimen.To identify strategies for reducing emesis induced by the CHOP regimen, which includes high-dose steroids, we prospectively evaluated the efficacy of palonosetron in Japanese patients. Palonosetron was administered at a dose of 0.75 mg via intravenous injection over 30 min before chemotherapy on day 1. Patients kept diaries of chemotherapy-induced nausea and vomiting (CINV) incidence from the start of chemotherapy until 168 h afterwards, in which they documented the occurrence and severity of nausea, vomiting, anorexia, and the use of rescue medication. The primary endpoint was the overall occurrence rate of nausea, vomiting, and anorexia; these rates were 56, 12, and 62 %, respectively, including all grades. The rates and severity of symptoms tended to worsen 120-168 h after completing oral prednisolone. We defined complete response (CR) as no vomiting and no use of rescue therapy. The CR rates of post palonosetron 0.75 mg treatment in the acute (0-24 h), delayed (24-168 h), and overall phases (0-168 h) were 86, 66, and 62 %, respectively. Antiemetic strategies of CHOP regimen for day 6 and, thereafter, should be investigated.2016年12月, International journal of hematology, 104(6) (6), 682 - 691, 英語, 国内誌研究論文（学術雑誌）
- 2016年, Bone Marrow Transplantation, 51, S411Absolute Lymphocyte Count Recovery Predicts Clinical Outcome after Allogeneic Hematopoietic Stem Cell Transplantation in a Japanese Population[査読有り]
- 2014年08月, Annals of hematology, 93(8) (8), 1435 - 8, 英語, 国際誌
- 2014年, Acta haematologica, 132(2) (2), 244 - 6, 英語, 国際誌Unbalanced translocation der(7)t(7q;11q): a new recurrent aberration leading to partial monosomy 7q and trisomy 11q in acute myeloid leukemia.研究論文（学術雑誌）
- Tolvaptan is an oral vasopressin V2-receptor antagonist recognized as effective for fluid retention associated with congestive heart failure and liver cirrhosis. However, there have been no reports concerning clinical experience with tolvaptan for sinusoidal obstruction syndrome (SOS). A 42-year-old male with primarily refractory T-lymphoblastic lymphoma underwent allogeneic peripheral blood stem cell transplantation from an HLA-matched sibling donor. The myeloablative conditioning regimen consisted of busulfan and cyclophosphamide. On day 20, the total bilirubin level was elevated to 2.0 mg/dL, and body weight increased from 76 to 85 kg, allowing a diagnosis of SOS to be made. Treatments with thrombomodulin, furosemide, carperitide, and low-dose dopamine were ineffective. By day 27, the patient's body weight had increased to 90 kg, and he subsequently developed cardiopulmonary failure. Therefore, we administered low-dose tolvaptan for 2 days (3.75 mg on day 27 and 7.5 mg on day 28). Consequently, his ascites and edema were significantly reduced, and body weight returned to 77 kg by day 34. However, he died of lymphoma progression on day 55. Tolvaptan may be an alternative and promising treatment for refractory fluid retention associated with SOS, although it is unclear whether tolvaptan administration leads to improvement in clinical outcome.2013年02月, International journal of hematology, 97(2) (2), 284 - 6, 英語, 国内誌研究論文（学術雑誌）
- BACKGROUND: In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), activating mutations of NOTCH1 are observed in more than 50% of cases, whereas the t(7;9)(q34;q34) involving NOTCH1 at 9q34 and TRB@ at 7q34 is an extremely rare but recurrent translocation. PATIENT: A 41-year-old male with a large mediastinal mass, pleural effusion, and lymphadenopathy was diagnosed as having T-LBL. Lymphoma cells were positive for CD4, CD8, CD2, CD3, CD5, CD7, CD10, and TdT. RESULTS: G-banding and spectral karyotyping of pleural effusion cells showed 47,XY,dup(1)(q21q32),t(7;9)(q34;q34),+20. Genomic polymerase chain reaction (PCR) revealed that the 5' end of TRB@ J1-5 was connected with the middle of NOTCH1 exon 25 (434 bp downstream from its 5' end) in a 'head-to-head' configuration on the der(9)t(7;9), although nine extra bases were inserted between the two genes. Reverse transcription-PCR confirmed expression of the TRB@/NOTCH1 fusion transcripts. Similarly, the 5' end of J1-5 was fused to the shortened exon 25 with nine extra bases. The NOTCH1 breakpoint in exon 25 was very close to transcription start sites of deleted Notch1 in murine T-ALL. CONCLUSIONS: The TRB@/NOTCH1 fusion gene with a NOTCH1 breakpoint in exon 25, which has not previously been detected in four other reported cases with t(7;9), could lead to aberrant expression of the truncated NOTCH1 by TRB@ enhancer elements. The resultant NOTCH1 receptor deleting most of the extracellular domain may be implicated in the pathogenesis of T-LBL by ligand-independent, constitutive activation of the NOTCH1 pathway, suggesting avenues for future therapy with γ-secretase inhibitors.2013年01月, European journal of haematology, 90(1) (1), 68 - 75, 英語, 国際誌研究論文（学術雑誌）
- Among B-cell non-Hodgkin's lymphomas, neural cell adhesion molecule/CD56 expression is exceptional. In this study, seven cases of CD56-positive diffuse large B-cell lymphoma (DLBCL) are described. The frequency of CD56-positive DLBCL was 7% in our hospital. Four of seven (57.1%) cases expressed both CD10 and bcl-6 suggestive of a germinal center B-cell phenotype. Six of seven (85.7%) cases expressed bcl-6. Two cases expressed aberrant T cell-associated antigens, one each of CD7 and CD8. However, none of these seven cases showed CD5 expression. No significant difference was observed between CD56-positive and CD56-negative DLBCL in terms of the five international prognostic index risk factors. However, all seven cases had at least one extranodal involvement and showed a good response to initial treatment. The predominance of extranodal involvement in our series may be associated with the adhesion-related function of CD56. A high frequency of bcl-6 expression may be associated with a more favorable clinical course and prognosis.2010年06月, Hematology (Amsterdam, Netherlands), 15(3) (3), 157 - 61, 英語, 国際誌研究論文（学術雑誌）
- 2024年, 日本血栓止血学会誌, 35(2) (2)進行・再発・転移の固形腫瘍における血栓塞栓症と出血リスク:PROVE-emboli試験post-hoc解析
- 2023年, 日本内科学会雑誌, 112がん関連静脈血栓塞栓症に対するアピキサバン療法の出血リスク予測:多施設共同第2相臨床試験副次的解析
- 2023年, 日本血栓止血学会誌, 34(2) (2)進行・再発・転移の未治療固形がん患者における静脈血栓塞栓症の前向き観察研究の統合解析
- (一社)日本臨床衛生検査技師会, 2022年05月, 日本医学検査学会抄録集, 71回, 474 - 474, 日本語バイオリソースセンター業務における臨床検査技師の役割
- (一社)日本臨床衛生検査技師会, 2022年05月, 日本医学検査学会抄録集, 71回, 475 - 475, 日本語神戸大学医学部附属病院バイオリソースセンターにおけるバイオバンクシステムの構築
- 2022年, 日本造血・免疫細胞療法学会総会プログラム・抄録集, 44th同種造血幹細胞移植後患者に対するSARS-CoV-2ワクチンの安全性と有効性
- (一社)日本血液学会, 2021年09月, 日本血液学会学術集会, 83回, PS - 2, 英語新たなKMT2A/EPS15融合遺伝子発現とt(1;11)(p32;q23)転座を認めたFLT3変異陽性B細胞性急性リンパ性白血病(Expression of a novel KMT2A/EPS15 fusion gene in FLT3 mutation-positive B-ALL with t(1;11)(p32;q23))
- (一社)日本血液学会, 2021年09月, 日本血液学会学術集会, 83回, PS - 6, 英語慢性GVHDに対する肝移植後の一過性末梢血マクロキメリズム(Transient macrochimerism following a liver transplant for hepatic GVHD after an allo-PBSCT)
- (一社)日本血液学会, 2021年09月, 日本血液学会学術集会, 83回, OS2 - 4, 英語自家造血幹細胞移植患者におけるsynbiotics投与の有効性についての臨床試験(Efficacy of synbiotics in auto-PBSCT patients: a prospective, double-blind, placebo-controlled trial)
- (一社)日本血液学会, 2021年09月, 日本血液学会学術集会, 83回, OS3 - 5, 英語同種移植におけるflash sensor-based glucose monitoringの安全性の検討(Safety and accuracy of flash sensor-based glucose monitoring devise in patients after Allo-HSCT)
- (一社)日本循環器学会, 2020年07月, 日本循環器学会学術集会抄録集, 84回, PE52 - 6, 英語Bleeding Events Associated with Anticoagulant Therapy; Apixaban in Japanese Patients with Cancer-associated Venous Thromboembolism: A Multicenter Phase II Trial(J-CAV)(和訳中)
- (一社)日本内科学会, 2020年02月, 日本内科学会雑誌, 109(Suppl.) (Suppl.), 226 - 226, 日本語2735人を対象とした悪性腫瘍関連静脈血栓塞栓症の合併率に関する後ろ向きコホート研究 甲状腺癌に対するチロシンキナーゼ阻害薬と血栓の関係
- (一社)日本内科学会, 2020年, 日本内科学会雑誌, 109(Suppl.) (Suppl.), 258 - 258, 日本語リソソーム機能活性化を介した抗体薬物複合体であるゲムツズマブオゾガマイシンの殺細胞効果増強法
- (一社)日本血液学会-東京事務局, 2018年09月, 臨床血液, 59(9号) (9号), 1733 - 1733, 日本語多発性筋炎様症状を呈したNK/T細胞リンパ腫(Extranodal NK/T-cell lymphoma mimicking polymyositis)(英語)[査読有り]
- (一社)日本血液学会-東京事務局, 2017年09月, 臨床血液, 58(9号) (9号), 1763 - 1763, 日本語悪性リンパ腫患者におけるコリンエステラーゼ値層別化による腫瘍崩壊症候群発症リスクの後方視的解析[査読有り]
- 2017年, 日本造血細胞移植学会総会プログラム・抄録集, 40th自家末梢血幹細胞移植における栄養状態と予後に関する後方視的解析
- (一社)日本血液学会-東京事務局, 2015年11月, 臨床血液, 56(11号) (11号), 2377 - 2377, 日本語30年来頸部腫瘤を有する患者より発症したDouble-hit lymphoma(DHL)の1例[査読有り]会議報告等
- AMER SOC HEMATOLOGY, 2014年12月, BLOOD, 124(21) (21), 英語Efficacy of the Two-Dose Influenza Vaccine in Cancer Patients Receiving Chemotherapy: A Prospective Study研究発表ペーパー・要旨（国際会議）
- (一社)日本血液学会-東京事務局, 2014年11月, 臨床血液, 55(11号) (11号), 2339 - 2339, 日本語腹部DLBCL病変出現1ヵ月前に発症したNeurolymphomatosisの1例会議報告等
- (一社)日本血液学会-東京事務局, 2014年09月, 臨床血液, 55(9号) (9号), 1271 - 1271, 日本語肺、大腸重複癌に合併した自己免疫性溶血性貧血における自己抗体の標的分子の同定
- 医療検査と自動化, 2022年08月, 日本語, (一社)日本医療検査科学会ニーズドリブン型バイオバンクを可能とするLIMSの構築
- 日本血液学会学術集会, 2021年09月, 英語, (一社)日本血液学会新たなKMT2A/EPS15融合遺伝子発現とt(1;11)(p32;q23)転座を認めたFLT3変異陽性B細胞性急性リンパ性白血病(Expression of a novel KMT2A/EPS15 fusion gene in FLT3 mutation-positive B-ALL with t(1;11)(p32;q23))
- 日本血液学会学術集会, 2021年09月, 英語, (一社)日本血液学会慢性GVHDに対する肝移植後の一過性末梢血マクロキメリズム(Transient macrochimerism following a liver transplant for hepatic GVHD after an allo-PBSCT)
- 日本血液学会学術集会, 2021年09月, 英語, (一社)日本血液学会自家造血幹細胞移植患者におけるsynbiotics投与の有効性についての臨床試験(Efficacy of synbiotics in auto-PBSCT patients: a prospective, double-blind, placebo-controlled trial)
- 日本血液学会学術集会, 2021年09月, 英語, (一社)日本血液学会同種移植におけるflash sensor-based glucose monitoringの安全性の検討(Safety and accuracy of flash sensor-based glucose monitoring devise in patients after Allo-HSCT)
- 日本循環器学会学術集会抄録集, 2020年07月, 英語, (一社)日本循環器学会Bleeding Events Associated with Anticoagulant Therapy; Apixaban in Japanese Patients with Cancer-associated Venous Thromboembolism: A Multicenter Phase II Trial(J-CAV)(和訳中)
- 日本内科学会雑誌, 2020年02月, 日本語, (一社)日本内科学会2735人を対象とした悪性腫瘍関連静脈血栓塞栓症の合併率に関する後ろ向きコホート研究 甲状腺癌に対するチロシンキナーゼ阻害薬と血栓の関係
- 日本内科学会雑誌, 2020年02月, 日本語, (一社)日本内科学会リソソーム機能活性化を介した抗体薬物複合体であるゲムツズマブオゾガマイシンの殺細胞効果増強法
- 臨床血液, 2018年09月, 英語, (一社)日本血液学会-東京事務局多発性筋炎様症状を呈したNK/T細胞リンパ腫(Extranodal NK/T-cell lymphoma mimicking polymyositis)
- 臨床血液, 2017年09月, 日本語, (一社)日本血液学会-東京事務局悪性リンパ腫患者におけるコリンエステラーゼ値層別化による腫瘍崩壊症候群発症リスクの後方視的解析
- 臨床血液, 2015年11月, 日本語, (一社)日本血液学会-東京事務局30年来頸部腫瘤を有する患者より発症したDouble-hit lymphoma(DHL)の1例
- 臨床血液, 2014年11月, 日本語, (一社)日本血液学会-東京事務局腹部DLBCL病変出現1ヵ月前に発症したNeurolymphomatosisの1例
- 臨床血液, 2014年09月, 日本語, (一社)日本血液学会-東京事務局肺、大腸重複癌に合併した自己免疫性溶血性貧血における自己抗体の標的分子の同定
- 日本検査血液学会2024年05月 - 現在
- 日本医療検査科学会2023年 - 現在
- 日本輸血・細胞治療学会2014年04月 - 現在
- 日本造血細胞・免疫細胞療法学会2011年08月 - 現在
- 日本血液学会2010年11月 - 現在
- 日本内科学会2007年12月 - 現在