101 results on '"Yoshimoto, G."'
Search Results
2. FLT3 mutations in normal karyotype acute myeloid leukemia in first complete remission treated with autologous peripheral blood stem cell transplantation
- Author
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Yoshimoto, G, Nagafuji, K, Miyamoto, T, Kinukawa, N, Takase, K, Eto, T, Kato, K, Hayashi, S, Kamimura, T, Ohno, Y, Taniguchi, S, and Harada, M
- Published
- 2005
- Full Text
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3. Disseminated tuberculosis following second unrelated cord blood transplantation for acute myelogenous leukemia
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Shima, T., Yoshimoto, G., Miyamoto, T., Yoshida, S., Kamezaki, K., Takenaka, K., Iwasaki, H., Harada, N., Nagafuji, K., Teshima, T., Shimono, N., and Akashi, K.
- Published
- 2009
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4. PS1065 OPEN-LABEL STUDY OF GILTERITINIB, GILTERITINIB PLUS AZACITIDINE, OR AZACITIDINE ALONE IN NEWLY DIAGNOSED FLT3-MUTATED AML PATIENTS INELIGIBLE FOR INTENSIVE CHEMOTHERAPY: RESULTS FROM THE SAFETY COHORT
- Author
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Esteve, J., primary, Schots, R., additional, Del Castillo, T. Bernal, additional, Lee, J.-H., additional, Wang, E., additional, Dinner, S., additional, Minden, M., additional, Salamero, O., additional, Sierra, J., additional, Yoshimoto, G., additional, Laribi, K., additional, Halka, J., additional, Montesinos, P., additional, Liu, S., additional, Rich, E., additional, and Bahceci, E., additional
- Published
- 2019
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5. Evaluation of the compliance with antiemetic guidelines for prevention of chemotherapy-induced nausea and vomiting in patients with hematologic malignancy
- Author
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Uchida, M., Nakamura, T., Shima, T., Mori, Y., Yoshimoto, G., Kato, K., Shimokawa, M., Hosohata, K., Miyamoto, T., and Akashi, K.
- Abstract
To assess compliance with the Japanese antiemetic guidelines for chemotherapy-induced nausea and vomiting (CINV), the frequencies of CINV occurrence and use of antiemetic rescue medications were examined in patients with hematological malignancy. A total of 40 patients with hematologic malignancy were eligible in this study. This study was performed in the Department of Hematology, Kyushu University Hospital, as a subgroup analysis from a nationwide, multicenter prospective cohort study conducted by the CINV Study Group of Japan. In the patients with hematological malignancy, the guideline compliance rate was 45 %. Five patients (22.7 %) experienced vomiting during the observation period after receiving non-guideline-consistent antiemetic prophylaxis, whereas no patient experienced vomiting after receiving guideline-consistent antiemetic prophylaxis. The study was not sufficiently powered to reach a statistical significance in its frequency of occurrence between the compliance and non-compliance groups. In the entire study period, 8 out of 40 patients required rescue medication, but there was no association between the status of compliance and the antiemetic guidelines. A total of 22 (55.0 %) patients achieved complete response, which was defined as no vomiting and no use of antiemetic rescue medication, during the study period. The rate of compliance with the prophylactic antiemetic treatment guidelines seemed to be low in patients with hematological malignancy, although the status of the guideline compliance did not always influence the antiemetic effects.
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- 2019
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6. Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis
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Nagafuji, K., primary, Nonami, A., additional, Kumano, T., additional, Kikushige, Y., additional, Yoshimoto, G., additional, Takenaka, K., additional, Shimoda, K., additional, Ohga, S., additional, Yasukawa, M., additional, Horiuchi, H., additional, Ishii, E., additional, and Harada, M., additional
- Published
- 2007
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7. 97: Rituximab-related late-onset neutropenia after autologous stem cell transplantation for malignant lymphoma
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Nagafuji, K., primary, Numata, A., additional, Yoshimoto, G., additional, Harada, N., additional, and Harada, M., additional
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- 2007
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8. Evaluation of bubble image by RFA tratment under ultrasonography for HCC and correlation with coagulation area
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Fujiwara, S, primary, Miyaji, K, additional, Hongou, Y, additional, Kojima, H, additional, Arisaka, Y, additional, Siozaki, M, additional, Ozawa, M, additional, Hashimoto, K, additional, Fukuda, A, additional, Teramura, K, additional, Yoshimoto, G, additional, Fukui, H, additional, Tanabe, T, additional, Kogita, S, additional, and Katsu, K, additional
- Published
- 2005
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9. Picosecond Time-Resolved Infrared Absorption Studies on the Photoexcited States of Poly(p-phenylenevinylene)
- Author
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Sakamoto, A., Nakamura, O., Yoshimoto, G., and Tasumi, M.
- Abstract
Picosecond time-resolved infrared absorption spectra of the photoexcited states of poly(p-phenylenevinylene) [(&sbd;C
6 H4 CH&dbd;CH&sbd;)n , PPV] have been observed with tunable picosecond light pulses obtained by difference-frequency generation between signal and idler waves from an optical parametric generator and amplifier. The time-resolved photoinduced infrared absorption bands due to a vibrational transition observed at 1550 cm-1 and an electronic transition at 3000 cm-1 of the photoexcited PPV have fast (≈1.7 ps) and slow (≈50 ps) decay components. By comparison of the picosecond time-resolved infrared absorption spectra of short-lived (fast decay component) and long-lived (slow decay component) transient species with the photoinduced and doping-induced infrared difference spectra of PPV, the short-lived transient species is assigned to bound polaron pairs, and the long-lived transient species is assigned to positive and negative polarons. - Published
- 2000
10. Textile Machinery Manufacturing and Machine Cutting Technic.
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Yoshimoto, G., primary
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- 1953
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11. On the mechanism of wear between metal surfaces
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Yoshimoto, G., primary and Tsukizoe, T., additional
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- 1958
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12. Manufacture of Textile Machinery and Mechanical Technology.
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Yoshimoto, G., primary
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- 1954
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13. Procalcitonin elevation in febrile recipients during pre-transplant conditioning with anti-thymocyte globulin.
- Author
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Shima T, Minami M, Tochigi T, Kochi Y, Jinnouchi F, Yamauchi T, Mori Y, Yoshimoto G, Mizuno S, Miyamoto T, Kato K, and Akashi K
- Abstract
Infection is a major contributor to non-relapse mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Detecting infectious diseases in febrile patients during pretransplant conditioning is crucial for subsequent transplant success. Procalcitonin (PCT) is an auxiliary diagnostic marker of severe bacterial infections and has been proposed as a useful predictor of infection in patients undergoing allo-HSCT. Pre-transplant use of anti-thymocyte globulin (ATG) can cause side effects, such as fever and hypotension, which must be distinguished from infectious diseases. Although ATG administration may increase PCT levels, data on PCT levels in febrile patients after ATG administration are limited. Furthermore, no studies have compared PCT levels during allo-HSCT conditioning using ATG or non-ATG regimens. To investigate whether ATG increases PCT levels during febrile episodes in pre-transplant conditioning and whether PCT could be used to discriminate infections during this period, we analyzed 17 ATG and 59 non-ATG patients with fever and who underwent PCT level measurements during pre-transplant conditioning. Our findings revealed that ATG administration was the only significant factor that increased PCT positivity during fever ( p = 0.01). In contrast, infectious diseases did not affect PCT positivity in the ATG group ( p = 0.24). Furthermore, bloodstream infection was a significant risk factor for PCT positivity in patients who received non-ATG regimens ( p < 0.01). Incorporating PCT levels into the diagnostic workup for infectious diseases requires careful consideration, particularly for patients receiving ATG regimens., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website., (Copyright Ⓒ2024 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)
- Published
- 2024
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14. Prognostic impact of HLA supertype mismatch in single-unit cord blood transplantation.
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Sugio T, Uchida N, Miyawaki K, Ohno Y, Eto T, Mori Y, Yoshimoto G, Kikushige Y, Kunisaki Y, Mizuno S, Nagafuji K, Iwasaki H, Kamimura T, Ogawa R, Miyamoto T, Taniguchi S, Akashi K, and Kato K
- Subjects
- Humans, Prognosis, Retrospective Studies, HLA Antigens, Histocompatibility Antigens, HLA-B Antigens genetics, Recurrence, Alleles, Histocompatibility Testing, Cord Blood Stem Cell Transplantation, Graft vs Host Disease
- Abstract
The "human leukocyte antigen (HLA) supertype" is a functional classification of HLA alleles, which was defined by structural features and peptide specificities, and has been reportedly associated with the clinical outcomes of viral infections and autoimmune diseases. Although the disparity in each HLA locus was reported to have no clinical significance in single-unit cord blood transplantation (sCBT), the clinical significance of the HLA supertype in sCBT remains unknown. Therefore, we retrospectively analyzed clinical data of 1603 patients who received sCBT in eight institutes in Japan between 2000 and 2017. Each HLA allele was categorized into 19 supertypes, and the prognostic effect of disparities was then assessed. An HLA-B supertype mismatch was identified as a poor prognostic factor (PFS: hazard ratio [HR] = 1.23, p = 0.00044) and was associated with a higher cumulative incidence (CI) of relapse (HR = 1.24, p = 0.013). However, an HLA-B supertype mismatch was not associated with the CI of acute and chronic graft-versus-host-disease. The multivariate analysis for relapse and PFS showed the significance of an HLA-B supertype mismatch independent of allelic mismatches, and other previously reported prognostic factors. HLA-B supertype-matched grafts should be selected in sCBT., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
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15. Impact of a third dose of anti-SARS-CoV-2 vaccine in hematopoietic cell transplant recipients: A Japanese multicenter observational study.
- Author
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Mori Y, Uchida N, Wake A, Miyawaki K, Eto T, Nakamura T, Iwasaki H, Ito Y, Tanimoto K, Katayama Y, Imamura Y, Takahashi T, Fujisaki T, Kamimura T, Choi I, Ishitsuka K, Yoshimoto G, Ogawa R, Sugita J, Takamatsu Y, Tanimoto K, Hidaka T, Miyamoto T, Akashi K, and Nagafuji K
- Subjects
- Humans, Antibodies, Viral, East Asian People, Transplant Recipients, COVID-19 prevention & control, Hematopoietic Stem Cell Transplantation, COVID-19 Vaccines administration & dosage
- Abstract
This prospective observational study aimed to assess the serological response and safety after the third booster shot of SARS-CoV-2 mRNA vaccines in 292 hematopoietic cell transplant (HCT) recipients. In our patients, mild systemic reactions were present in 10-40% and GVHD aggravation in 1.1%. Overall, clinically relevant response (>250 U/mL) was observed in 93.1% of allogeneic (allo)-HCT recipients and 70.6% of autologous (auto)-HCT recipients, respectively. Of note, detectable antibody response with any titer following the first two doses was a powerful predictor for adequate response after booster shot in both cohorts. For such patients, 98.8% of allo- and 92.3% of auto-HCT recipients obtained clinically relevant response after dose 3. In addition, continued systemic steroid and/or calcineurin inhibitors at the booster shot significantly correlated with serological response. These findings highlighted that booster vaccination efficiently improved serological response without safety concerns and thus recommended for the majority of HCT recipients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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16. Successful pseudo-autologous stem cell transplantation for donor-derived Burkitt lymphoma occurring 9 years after allogeneic transplantation.
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Taniguchi S, Utsumi S, Kochi Y, Taya Y, Mori Y, Semba YI, Sugio T, Miyawaki K, Kikushige Y, Kunisaki Y, Yoshimoto G, Numata A, Kato K, Uchida N, Maeda T, Miyamoto T, Taniguchi S, and Akashi K
- Subjects
- Humans, Transplantation, Autologous, Transplantation, Homologous adverse effects, Immunosuppressive Agents, Hematopoietic Stem Cell Transplantation adverse effects, Burkitt Lymphoma etiology, Burkitt Lymphoma therapy, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Graft vs Host Disease pathology, Lymphoma complications, Leukemia, Myeloid, Acute complications
- Abstract
Donor-derived hematological malignancies have been recognized as rare but serious late complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Most cases in the literature were diagnosed as myelodysplastic syndrome or acute leukemia, with very few malignant lymphoma reported. We herein present another case of donor-derived Burkitt lymphoma that occurred 9 years after allo-HSCT under continued administration of immunosuppressants for chronic graft-versus-host disease (GVHD). The patient achieved a partial response after rituximab-combined intensive chemotherapy. To reduce the risk of relapse and to avoid organ toxicities due to repeated chemotherapies, we performed upfront high-dose chemotherapy followed by stem cell rescue using donor-derived CD34
+ cells, called pseudo-autologous HSCT (pASCT), and adjusted immunosuppressants appropriately. The patient remained disease-free for 23 months after pASCT without exacerbation of cGVHD. Although the observation period has been relatively short and longer follow-up is needed, pASCT may be a feasible option for donor-derived lymphoma even in patients with active cGVHD., (© 2022. Japanese Society of Hematology.)- Published
- 2023
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17. Predictors of impaired antibody response after SARS-CoV-2 mRNA vaccination in hematopoietic cell transplant recipients: A Japanese multicenter observational study.
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Mori Y, Uchida N, Harada T, Katayama Y, Wake A, Iwasaki H, Eto T, Morishige S, Fujisaki T, Ito Y, Kamimura T, Takahashi T, Imamura Y, Tanimoto K, Ishitsuka K, Sugita J, Kawano N, Tanimoto K, Yoshimoto G, Choi I, Hidaka T, Ogawa R, Takamatsu Y, Miyamoto T, Akashi K, and Nagafuji K
- Subjects
- Humans, Antibodies, Viral, Antibody Formation, COVID-19 Vaccines administration & dosage, COVID-19 Vaccines adverse effects, East Asian People, RNA, Messenger, SARS-CoV-2, Transplant Recipients, Vaccination, Japan, COVID-19 prevention & control, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
HCT recipients reportedly have a high mortality rate after developing COVID-19. SARS-CoV-2 vaccination is generally useful to prevent COVID-19. However, its safety and efficacy among HCT recipients remain elusive. This large-scale prospective observational study including 543 HCT recipients with 37-months interval from transplant demonstrated high safety profiles of mRNA vaccine: only 0.9% of patients avoided the second dose due to adverse event or GVHD aggravation following the first dose. Regarding the efficacy, serological response with a clinically relevant titer (≥250 BAU/mL) was obtained in 397 (73.1%) patients. We classified the remaining 146 patients as impaired responders and compared the clinical and immunological parameters between two groups. In allogeneic HCT recipients, multivariable analysis revealed the risk factors for impaired serological response as follows: age (≥60, 1 points), HLA-mismatched donor (1 points), use of systemic steroids (1 points), absolute lymphocyte counts (<1000/μL, 1 points), absolute B-cell counts (<100/μL, 1 points), and serum IgG level (<500 mg/dL, 2 points). Notably, the incidence of impaired serological response increased along with the risk scores: patients with 0, 1-3, and 4-7 points were 3.9%, 21.8%, and 74.6%, respectively. In autologous HCT recipients, a shorter interval from transplant to vaccination was the only risk factor for impaired serological response. Our findings indicate that two doses of SARS-CoV-2 vaccine are safe but insufficient for a part of HCT recipients with higher risk scores. To improve this situation, we should consider additional treatment options, including booster vaccination and prophylactic neutralizing antibodies during the SARS-CoV-2 pandemic., (© 2022 Wiley Periodicals LLC.)
- Published
- 2023
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18. [Maintenance therapy after allogeneic hematopoietic stem cell transplantation].
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Yoshimoto G and Miyamoto T
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- Humans, Neoplasm Recurrence, Local, Retrospective Studies, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute pathology
- Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved survival for patients with hematological malignancy, especially for those highly at risk of relapse. However, disease relapse after allo-HSCT remains the most common cause of treatment failure and death, even with conventional chemotherapy and donor lymphocyte infusion. Disease relapse in allo-HSCT can be reduced via pre-emptive treatment based on measurable residual disease and maintenance therapy for patients at high risk of relapse as promising treatment strategies. Recently, the development of novel agents and cellular therapies with high antitumor activity and less toxicity, which can be used in the post-transplant setting, has increased their clinical applications in the therapeutic approach. This review examines the current landscape and future strategies for maintenance therapy, mainly for AML and ALL after allo-HSCT.
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- 2023
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19. Prognostic value of pre-transplantation total metabolic tumor volume on 18 fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography in relapsed and refractory aggressive lymphoma.
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Sugio T, Baba S, Mori Y, Yoshimoto G, Kamesaki K, Takashima S, Urata S, Shima T, Miyawaki K, Kikushige Y, Kunisaki Y, Numata A, Takenaka K, Iawasaki H, Miyamoto T, Ishigami K, Akashi K, and Kato K
- Subjects
- Fluorodeoxyglucose F18, Glucose, Humans, Neoplasm Recurrence, Local diagnostic imaging, Neoplasm Recurrence, Local therapy, Neoplasm, Residual, Positron Emission Tomography Computed Tomography, Prognosis, Retrospective Studies, Tumor Burden, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Lymphoma, Non-Hodgkin
- Abstract
Relapsed and refractory aggressive lymphoma have a poor prognosis. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is effective in chemosensitive patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is among the few options for non-chemosensitive patients.
18 Fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18 FDG-PET/CT) is the standard tool for evaluating response to chemotherapy and residual tumor volume. However, accurate assessment of residual tumor volume is not currently being achieved in clinical practice, and its value in prognostic and therapeutic stratification remains unclear. To answer this question, we investigated the efficacy of quantitative indicators, including total metabolic tumor volume (TMTV), in predicting prognosis after auto-HSCT and allo-HSCT. We retrospectively analyzed 39 patients who received auto-HSCT and 28 who received allo-HSCT. In the auto-HSCT group, patients with a higher TMTV had a poor prognosis due to greater risk of relapse. In the allo-HSCT group, patients with a higher TMTV had a lower progression-free survival rate and a significantly higher relapse rate. Neither Deauville score nor other clinical parameters were associated with prognosis in either group. Therefore, pre-transplant TMTV on PET is effective for prognostic prediction and therapeutic decision-making for relapsed or refractory aggressive lymphoma., (© 2022. Japanese Society of Hematology.)- Published
- 2022
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20. Risk factors for late cytomegalovirus infection after completing letermovir prophylaxis.
- Author
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Mori Y, Harada T, Yoshimoto G, Shima T, Numata A, Jinnouchi F, Yamauchi T, Kikushige Y, Kunisaki Y, Kato K, Takenaka K, Akashi K, and Miyamoto T
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- Acetates, Antiviral Agents therapeutic use, Humans, Quinazolines, Retrospective Studies, Risk Factors, Cytomegalovirus Infections epidemiology, Cytomegalovirus Infections etiology, Cytomegalovirus Infections prevention & control, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Prophylactic use of letermovir (LMV) markedly reduces the incidence of early clinically significant cytomegalovirus (csCMV) infection within the first 100 days after allogeneic hematopoietic cell transplantation (allo-HCT), which improves transplant outcomes. However, some patients eventually develop late-csCMV infection (beyond day 100) after completing LMV prophylaxis. To assess the incidence of late-csCMV infection as well as its risk factors and impacts on transplant outcome, a total of 81 allo-HCT recipients who had not developed early csCMV infection during LMV prophylaxis were retrospectively analyzed. Among them, 23 (28.4%) patients developed late-csCMV infection (until day 180) at a median time of 131 days after transplantation and 30 days after LMV discontinuation, respectively. Late-csCMV infection was correlated with apparent delayed immune reconstitution: patients transplanted from HLA-mismatched donors (hazard ratio [HR] = 13.0, p = 0.011) or CMV-IgG-negative donors (HR = 2.39, p = 0.043) had a significantly higher risk. In this study, transplant outcomes did not differ between patients with and without late-csCMV infection. This suggests a need to clarify the efficacy of extended administration of LMV for preventing late-csCMV infection in a larger number of allo-HCT recipients, especially those with "high-risk" donors., (© 2022. Japanese Society of Hematology.)
- Published
- 2022
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21. Development and Validation of an LC-MS/MS Method to Quantify Gilteritinib and Its Clinical Application in Patients With FLT3 Mutation-Positive Acute Myelogenous Leukemia.
- Author
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Zhang M, Tajima S, Suetsugu K, Hirota T, Tsuchiya Y, Yamauchi T, Yoshimoto G, Miyamoto T, Egashira N, Akashi K, and Ieiri I
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- Aniline Compounds, Chromatography, High Pressure Liquid methods, Chromatography, Liquid, Humans, Limit of Detection, Mutation, Pyrazines, Reproducibility of Results, fms-Like Tyrosine Kinase 3 genetics, fms-Like Tyrosine Kinase 3 therapeutic use, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Tandem Mass Spectrometry methods
- Abstract
Background: Gilteritinib, a novel oral tyrosine kinase inhibitor, is used to treat acute myeloid leukemia (AML) with FMS-like tyrosine kinase-3 (FLT3) mutations. Therapeutic drug monitoring (TDM) of gilteritinib is important for improving clinical outcomes and ensuring safety. Therefore, this study aimed to develop a simplified method for quantifying gilteritinib in human plasma using liquid chromatography-tandem mass spectrometry., Methods: Liquid chromatography was performed by using an Acquity BEH C18 column (50 mm × 2.1 mm, 1.7 μm) and a gradient elution with 0.1% formic acid in water (A) and acetonitrile (B). Detection was performed by using a Shimadzu tandem mass spectrometer through multiple reaction monitoring in the positive-ion mode., Results: The developed method enabled quantification of gilteritinib in 4 minutes and was validated by evaluating selectivity, calibration curve (10-1000 ng/mL, r 2 > 0.99), a lower limit of quantification (LLOQ), accuracy (overall bias -4.2% to 1.9%), precision (intraday CV ≤ 7.9%; interday CV ≤ 13.6%), carryover, recovery, matrix effect, dilution integrity, and stability according to the US Food and Drug Administration (FDA) guidelines. This method was successfully applied to the TDM of gilteritinib trough concentrations in 3 patients with AML., Conclusions: The developed method fulfilled the FDA guideline criteria and can easily be implemented to facilitate TDM in patients receiving gilteritinib in a clinical setting., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
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22. [Ⅰ. Anti-CD33 Antibody-Based Drugs].
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Yoshimoto G and Miyamoto T
- Subjects
- Humans, Sialic Acid Binding Ig-like Lectin 3, Leukemia, Myeloid, Acute
- Published
- 2022
23. Early-onset cardiac dysfunction following allogeneic haematopoietic stem cell transplantation.
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Moriyama S, Fukata M, Hieda M, Yokoyama T, Yoshimoto G, Kusaba H, Nakashima Y, Miyamoto T, Maruyama T, and Akashi K
- Subjects
- Humans, Retrospective Studies, Stroke Volume, Ventricular Function, Left, Graft vs Host Disease etiology, Heart Diseases complications, Hematologic Neoplasms complications, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Objective: Heart failure following allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a serious complication that requires early detection; however, the clinical implications of early-onset cancer therapy-related cardiac dysfunction (CTRCD) following allo-HSCT remain unclear. We investigated the determinants and prognostic impact of early-onset CTRCD in allo-HSCT recipients., Methods: The records of 136 patients with haematological malignancies who underwent allo-HSCT at our institute were retrospectively reviewed. Early-onset CTRCD was defined as a decrease in left ventricular ejection fraction (LVEF) of ≥10% and an LVEF of ≤53% within 100 days after HSCT., Results: Early-onset CTRCD was diagnosed in 23 out of 136 included patients (17%), and the median duration from HSCT to CTRCD diagnosis was 24 (9-35) days. Patients were followed up for 347 (132-1268) days. In multivariate logistic regression analysis, cumulative doxorubicin dosage (each 10 mg/m
2 ) and severity of acute graft-versus-host disease (GVHD/grade) were independent indicators of early-onset CTRCD (OR (95% CI) 1.04 (1.00 to 1.07); p=0.032; OR (95% CI) 1.87 (1.19 to 2.95), p=0.004, respectively). The overall and primary disease death rates were significantly higher in allo-HSCT recipients with early-onset CTRCD than in those without early-onset CTRCD (HR (95% CI) 1.98 (1.11 to 3.52), p=0.016; HR (95% CI) 2.96 (1.40 to 6.29), p=0.005, respectively), independent of primary disease type, remission status and transplantation type., Conclusions: Severe acute GVHD and higher cumulative anthracycline are two significant determinants of early-onset CTRCD. Early-onset CTRCD following allo-HSCT regulates survival in patients with haematological malignancies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)- Published
- 2022
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24. Incidence of refractory cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation.
- Author
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Jinnouchi F, Mori Y, Yoshimoto G, Yamauchi T, Nunomura T, Yurino A, Hayashi M, Yuda J, Shima T, Odawara J, Takashima S, Kamezaki K, Kato K, Miyamoto T, Akashi K, and Takenaka K
- Subjects
- Adolescent, Adult, Aged, Cytomegalovirus genetics, Cytomegalovirus physiology, Cytomegalovirus Infections prevention & control, Cytomegalovirus Infections virology, Drug Resistance, Viral genetics, Female, Humans, Immunocompromised Host, Incidence, Infection Control, Male, Middle Aged, Mutation, Postoperative Complications prevention & control, Prospective Studies, Young Adult, Cytomegalovirus Infections epidemiology, Cytomegalovirus Infections etiology, Hematopoietic Stem Cell Transplantation adverse effects, Postoperative Complications epidemiology, Postoperative Complications etiology, Transplantation, Homologous adverse effects
- Abstract
Post-transplant cytomegalovirus (CMV) disease can be almost completely avoided by current infection control procedures. However, CMV reactivation occurs in more than half of patients, and some patients can develop clinically resistant CMV infections. Whether resistance is due to the host's immune status or a viral resistance mutation is challenging to confirm. Therefore, a prospective observational analysis of refractory CMV infection was conducted in 199 consecutive patients who received allogeneic hematopoietic stem cell transplantation at a single institution. Among them, 143 (72%) patients received anti-CMV drugs due to CMV reactivation, and only 17 (8.5%) exhibited refractory CMV infection. These patients had clinically refractory infection. However, viral genome analysis revealed that only one patient exhibited a mutation associated with the anti-CMV drug resistance. Clinical resistance was mainly correlated with host immune factors, and the incidence of resistance caused by gene mutations was low at the early stage after a transplantation., (© 2021. Japanese Society of Hematology.)
- Published
- 2022
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25. Azacitidine for the treatment of patients with relapsed acute myeloid leukemia after allogeneic stem cell transplantation.
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Yoshimoto G, Mori Y, Kato K, Odawara J, Kuriyama T, Ueno T, Obara T, Yurino A, Yoshida S, Ogawa R, Ohno Y, Iwasaki H, Eto T, Akashi K, and Miyamoto T
- Subjects
- Azacitidine therapeutic use, Humans, Retrospective Studies, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute therapy
- Abstract
We retrospectively analyzed 38 patients with AML who received azacitidine (AZA) to treat disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with objective response (OR) ( n = 20) after AZA had significantly higher 2-year overall survival (OS) (45.0% vs 5.6%; p = 0.004) than progressive disease. The 2-year OS was significantly higher in the retransplant group ( n = 23) than in the nonretransplant group ( n = 15) (34.8% vs 13.3%; p = 0.034). We analyzed 167 patients who underwent the second allo-HSCT to clarify the impact of pretransplant AZA after the second allo-HSCT. Patients in the AZA group ( n = 21) had significantly higher 2-year disease-free survival (DFS) (32.7% vs 14.5%; p = 0.012) and OS (38.1% vs 17.5%; p = 0.044) than those in the SOC group ( n = 146). Our data demonstrate that AZA is an effective and well-tolerated bridging therapy to the second allo-HSCT.
- Published
- 2021
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26. Outcomes of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs.
- Author
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Harada T, Iwasaki H, Muta T, Urata S, Sakamoto A, Kohno K, Takase K, Miyamura T, Sawabe T, Asaoku H, Oryoji K, Fujisaki T, Mori Y, Yoshimoto G, Ayano M, Mitoma H, Miyamoto T, Niiro H, Yamamoto H, Oshiro Y, Miyoshi H, Ohshima K, Takeshita M, Akashi K, and Kato K
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bleomycin administration & dosage, Cyclophosphamide administration & dosage, Dacarbazine administration & dosage, Doxorubicin administration & dosage, Female, Follow-Up Studies, Humans, Janus Kinases antagonists & inhibitors, Kaplan-Meier Estimate, Lymphoma, Non-Hodgkin mortality, Lymphoproliferative Disorders chemically induced, Lymphoproliferative Disorders mortality, Male, Methotrexate therapeutic use, Middle Aged, Prednisone administration & dosage, Progression-Free Survival, Proportional Hazards Models, Rituximab administration & dosage, Treatment Outcome, Tumor Necrosis Factor-alpha antagonists & inhibitors, Vinblastine administration & dosage, Vincristine administration & dosage, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid drug therapy, Lymphoproliferative Disorders drug therapy, Methotrexate adverse effects
- Abstract
Recently, the use of targeted synthetic or biological disease-modifying anti-rheumatic drugs (ts/bDMARDs) in addition to conventional synthetic (cs)DMARDs including methotrexate (MTX) for rheumatoid arthritis (RA) has increased. However, whether ts/bDMARDs are associated with the development and clinicopathological features of MTX-associated lymphoproliferative disorder (MTX-LPD) in patients with RA remains unknown. Therefore, we evaluated the clinical outcomes of 121 patients with MTX-LPD. Results showed that prior use of ts/bDMARDs was not associated with the different histopathological subtypes of MTX-LPD. Patients with polymorphic-type LPD had a better event-free survival than those with diffuse large B-cell lymphoma (DLBCL), classical Hodgkin lymphoma and peripheral T-cell lymphoma. The pathological subtype of lymphoma could predict the clinical outcome of MTX-LPD. In patients with DLBCL, the use of tumour necrosis factor-alpha (TNF-α) inhibitors prior to MTX-LPD onset was associated with a higher non-relapse mortality. Further, patients with RA previously treated with Janus kinase (JAK) inhibitors more commonly required chemotherapy than those treated with csDMARDs alone, indicating disease aggressiveness. Hence, special caution should be observed when managing patients with MTX-LPD previously treated with JAK or TNF-α inhibitors for RA., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2021
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27. Efficacy of prophylactic letermovir for cytomegalovirus reactivation in hematopoietic cell transplantation: a multicenter real-world data.
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Mori Y, Jinnouchi F, Takenaka K, Aoki T, Kuriyama T, Kadowaki M, Odawara J, Ueno T, Kohno K, Harada T, Yoshimoto G, Takase K, Henzan H, Kato K, Ito Y, Kamimura T, Ohno Y, Ogawa R, Eto T, Nagafuji K, Akashi K, and Miyamoto T
- Subjects
- Acetates, Antiviral Agents therapeutic use, Cytomegalovirus, Humans, Quinazolines, Retrospective Studies, Cytomegalovirus Infections drug therapy, Cytomegalovirus Infections prevention & control, Hematopoietic Stem Cell Transplantation
- Abstract
A novel anti-cytomegalovirus (CMV) agent, letermovir (LMV), could reportedly improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients because of its high potential to prevent CMV reactivation. Therefore, 685 Japanese allo-HCT recipients, of whom ~80% had a high risk of CMV reactivation, were retrospectively analyzed to assess the impacts of prophylactic LMV on the incidence of clinically significant CMV (csCMV) infection as well as their transplant outcome. By comparing 114 patients who received LMV prophylaxis for a median 92 days to 571 patients without prophylaxis, we observed that prophylactic LMV could significantly (1) reduce the 180-day cumulative incidence of csCMV infection (44.7 vs. 72.4%, p < 0.001), (2) delay the median time until initiation of CMV antigenemia-guided preemptive therapy (90 vs. 36 days, p < 0.001), (3) shorten the duration of anti-CMV preemptive treatment (21 vs. 25 days, p = 0.006), and (4) improve the overall survival rate at 180 days after transplant (80.4 vs. 73.0%, p = 0.033) with a trend of lower non-relapse mortality (8.9 vs. 14.9%, p = 0.052). Our findings demonstrate that prophylactic LMV treatment is highly effective in preventing the development of csCMV infection and ultimately reduces transplant-related mortality.
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- 2021
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28. [Stratified treatment of fit and unfit acute myeloid leukemia].
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Yoshimoto G
- Subjects
- Chromosome Aberrations, Genomics, Humans, Mutation, Prognosis, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
- Abstract
The etiology and pathogenesis of acute myeloid leukemia (AML) have been elucidated at chromosomal and genetic levels. The classification and prognosis for its treatment has clearly involved specific chromosomal aberrations and genetic mutations. The recent comprehensive genomic analysis represented by next-generation sequencers has led to discovering new genetic mutations in AML. These findings have not only been applied clinically as prognostic factors and MRD markers but also contributed to the development of new molecular-targeting drugs. Many new drugs have already been approved in the USA and Europe, and new stratified treatments have tried to incorporate them. With the advent of venetoclax, treatment strategies, especially for patients with poor prognosis and who are unfit, have been substantially revised, and the maintenance therapy for AML is also being reevaluated in accordance to the National Comprehensive Cancer Network guidelines. This article will review the current status of AML treatment in Japan and according to Western guidelines.
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- 2021
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29. Low-dose anti-thymocyte globulin for GVHD prophylaxis in HLA-matched allogeneic peripheral blood stem cell transplantation.
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Shiratori S, Sugita J, Ota S, Kasahara S, Ishikawa J, Tachibana T, Hayashi Y, Yoshimoto G, Eto T, Iwasaki H, Harada M, Matsuo K, and Teshima T
- Subjects
- Antilymphocyte Serum, Bone Marrow Transplantation, Humans, Middle Aged, Transplantation Conditioning, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Peripheral Blood Stem Cell Transplantation
- Abstract
Allogeneic peripheral blood stem cell transplantation (PBSCT) is associated with an increased risk of severe acute and chronic graft-versus-host disease (GVHD) compared to bone marrow transplantation. Anti-thymocyte globulin (ATG) can reduce severe acute and chronic GVHD in PBSCT; however, an optimal dose of ATG remains undefined. We conducted a multicenter phase II study to investigate safety and efficacy of low-dose ATG (a total of 2 mg/kg Thymoglobulin) in patients undergoing HLA-matched PBSCT after myeloablative conditioning. The primary endpoint was grades III-IV GVHD at 100 days. Seventy-seven patients were enrolled and 72 patients with a median age of 46.5 years were eligible for analysis. The primary endpoint, cumulative incidence of grades III-IV acute GVHD at 100 days was 1.4% (95% CI, 0.1-6.7%), which was greatly less than our pre-defined statistical threshold value (18.0%). The incidence of chronic GVHD at 1 year was also low (all-grade; 15.3%, moderate to severe; 5.6%). Non-relapse mortality, relapse, overall survival, disease-free survival, and GVHD-free, relapse-free survival at 1 year were 4.2%, 20.8%, 84.7%, 75.0%, and 69.4%, respectively. Low dose thymoglobulin is promising to reduce severe acute and chronic GVHD in HLA-matched PBSCT following myeloablative conditioning.
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- 2021
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30. Outcome predictors after retransplantation in relapsed acute lymphoblastic leukemia: a multicenter, retrospective study.
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Mori Y, Sasaki K, Ito Y, Kuriyama T, Ueno T, Kadowaki M, Aoki T, Sugio T, Yoshimoto G, Kato K, Maeda T, Nagafuji K, Akashi K, and Miyamoto T
- Subjects
- Adolescent, Adult, Aged, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Middle Aged, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Prognosis, Retreatment mortality, Retreatment trends, Retrospective Studies, Survival Rate trends, Transplantation Conditioning mortality, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation trends, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation Conditioning trends
- Abstract
Retransplantation is the only curative treatment option for patients with acute lymphoblastic leukemia (ALL) that has relapsed after allogeneic hematopoietic cell transplantation (allo-HCT); however, data in this setting remain scant. Hence, this multicenter, retrospective study aims to determine outcome predictors after retransplantation in relapsed ALL. We examined 55 recipients who underwent multiple allo-HCTs during 2006-2018. The 2-year overall survival (OS), progression-free survival (PFS), and non-relapse mortality rates were 35.9%, 29.1%, and 23.6%, respectively. We observed a trend of better outcome in Ph + ALL (n = 22) patients compared with non-Ph ALL (n = 33) patients; the 2-year PFS was 40.9% versus 21.2%, indicating a beneficial effect of more potent second- or third-generation tyrosine kinase inhibitors. Univariate analysis revealed that late relapse after the previous transplant was the only significant predictor of better transplant outcome among Ph + ALL patients, whereas factors related to prolonged OS/PFS in non-Ph ALL patients were late relapse after the previous transplant, longer duration from disease relapse/progression to second or more allo-HCT, disease status at the transplantation, and good performance status. Nevertheless, further investigations are warranted to determine whether novel molecular-targeted agents with higher efficacy and fewer toxicities could exceed conventional chemotherapies as a bridging strategy to next allo-HCT and improve the outcomes of non-Ph ALL patients.
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- 2021
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31. Myeloablative intravenous busulfan-containing regimens for allo-HSCT in AML or MDS patients over 54 years old: combined results of three phase II studies.
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Uchida N, Matsumoto K, Sakura T, Hidaka M, Miyamoto T, Eto T, Maeda Y, Murayama T, Fujishima N, Yoshimoto G, Morita K, Kishimoto J, Teshima T, Taniguchi S, Yamashita T, Mori SI, Akashi K, and Harada M
- Subjects
- Age Factors, Aged, Busulfan adverse effects, Clinical Trials, Phase II as Topic, Disease-Free Survival, Female, Humans, Infusions, Intravenous, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Myelodysplastic Syndromes mortality, Prospective Studies, Radiation Dosage, Transplantation, Homologous, Treatment Outcome, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Whole-Body Irradiation methods, Busulfan administration & dosage, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy, Transplantation Conditioning methods
- Abstract
An optimal pretransplant conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in older adults has not been established. Three prospective multicenter phase II studies were conducted, in which 142 patients older than 54 years (median age, 61 years; range 55-70 years) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) received a myeloablative dose of intravenous busulfan (ivBu, 12.8 mg/kg) along with fludarabine (180 mg/m
2 ) ± low dose total body irradiation for allo-HSCT between September 2009 and February 2013. A total of 103 AML and 39 MDS patients including 21 related bone marrow (BM) or peripheral blood (PB), 50 unrelated BM, and 71 unrelated cord blood (UCB) transplantation were enrolled. Grade 3 or greater toxicities were observed in 105 patients. Neutrophil engraftment was achieved in 70 out of the 71 related PB/BM or unrelated BM recipients, and 61 out of the 71 UCB recipients. The cumulative incidence rates of relapse and non-relapse mortality after 2 years were 24.0 and 24.1%, respectively. The overall and event-free survival rates at 2 years were 53.3 and 47.4%, respectively. The myeloablative dose of ivBu was well tolerated without increased toxicity-related mortality in older adults who underwent allo-HSCT with any donor source.- Published
- 2020
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32. Correction to: Measurable residual disease after the first consolidation predicts the outcomes of patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy.
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Henzan H, Takase K, Kamimura T, Mori Y, Yoshimoto G, Iwasaki H, Nagafuji K, Ogawa R, Eto T, Uchida N, Fujisaki T, Kato K, Minami M, Kikushige Y, Akashi K, and Miyamoto T
- Abstract
In the original publication of the article, the "CNS involvement" in the last row under the column "Total N=50" has been published incorrectly. The correct Table 1 is given in this correction.
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- 2020
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33. Measurable residual disease after the first consolidation predicts the outcomes of patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy.
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Henzan H, Takase K, Kamimura T, Mori Y, Yoshimoto G, Iwasaki H, Nagafuji K, Ogawa R, Eto T, Uchida N, Fujisaki T, Kato K, Minami M, Kikushige Y, Akashi K, and Miyamoto T
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cytarabine administration & dosage, Female, Forecasting, Humans, Idarubicin administration & dosage, Leukemia, Promyelocytic, Acute mortality, Male, Middle Aged, Neoplasm, Residual diagnosis, Prognosis, Prospective Studies, Recurrence, Survival Rate, Treatment Outcome, Tretinoin administration & dosage, Young Adult, Consolidation Chemotherapy, Leukemia, Promyelocytic, Acute drug therapy, Neoplasm, Residual mortality, Tretinoin therapeutic use
- Abstract
We stratified patients with newly diagnosed acute promyelocytic leukemia (APL) according to a white blood cell (WBC) count of ≥ 3 × 10
9 /L (high risk) or < 3 × 109 /L (low risk) before administering risk-adapted chemotherapy in combination with all-trans retinoic acid (ATRA). In total, 27 low-risk and 23 high-risk patients were assigned to receive induction and three courses of consolidation with ATRA and anthracycline, followed by 2-year maintenance regimen. High-risk group additionally received cytarabine during 1st consolidation and another one-shot idarubicin treatment during 3rd consolidation. We prospectively monitored measurable residual disease (MRD) after induction and each consolidation. In the low-risk and high-risk groups, 5-year disease-free survival (DFS) rates were 86.5% and 81.2% (p = 0.862), and 5-year overall survival rates were 100% and 84.8% (p = 0.062), respectively. In the MRD-negative and MRD-positive groups, 5-year DFS rates were 91.7% and 78.4% (p = 0.402) and 84.7% and 60.0% (p = 0.102) after induction and 1st consolidation, respectively. Relapse rates were 8.3% and 13.3% (p = 0.570) and 9.0% and 40.0% (p = 0.076) after induction and 1st consolidation, respectively. Achieving MRD-negativity after 1st consolidation, rather than after induction, was a potential predictor of relapse and DFS in patients with APL treated with ATRA + chemotherapy.- Published
- 2020
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34. HTLV-1 seropositive patients with lung cancer treated with PD-1 inhibitors.
- Author
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Yoneshima Y, Kato K, Minami H, Ikeda M, Watanabe H, Yoshimoto G, Miyamoto T, Akashi K, Nakanishi Y, and Okamoto I
- Subjects
- Aged, Antibodies, Monoclonal, Humanized adverse effects, Asymptomatic Infections, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung immunology, Carrier State blood, Carrier State immunology, Carrier State virology, Follow-Up Studies, HTLV-I Antibodies blood, HTLV-I Antibodies immunology, HTLV-I Infections chemically induced, HTLV-I Infections immunology, HTLV-I Infections virology, Human T-lymphotropic virus 1 isolation & purification, Humans, Lung Neoplasms drug therapy, Lung Neoplasms immunology, Male, Middle Aged, Nivolumab adverse effects, Programmed Cell Death 1 Receptor immunology, Retrospective Studies, Antineoplastic Agents, Immunological adverse effects, Carrier State diagnosis, HTLV-I Infections diagnosis, Human T-lymphotropic virus 1 immunology, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Published
- 2020
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35. Epstein-Barr Virus-Associated Encephalopathy Presenting with Nonconvulsive Status Epilepticus in an Immunosuppressive State.
- Author
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Ohya Y, Nakamura K, Wakisaka Y, Sato H, Wakisaka K, Kumamoto M, Muraya Y, Kuroda J, Nakane H, Yoshimoto G, Kitazono T, and Ago T
- Abstract
Epstein-Barr virus (EBV) infection is occasionally accompanied by central nervous system (CNS) complications, particularly in immunosuppressed patients. However, the symptoms and clinical features of EBV infection in the CNS are rather heterogeneous and remain unknown. We herein describe the first reported adult case manifesting nonconvulsive status epilepticus (NCSE), possibly associated with reactivation of EBV in an immunosuppressive state. A 63-year-old man with a history of acute myeloid leukemia and taking immunosuppressants was admitted due to progressively impaired consciousness without any focal neurological signs, including paralysis or convulsions. Arterial spin labeling magnetic resonance imaging (ASL-MRI) and brain perfusion single-photon emission computed tomography showed hyperperfusion in the right temporal region, despite no morphological abnormalities in other MRI sequences. White blood cell counts, EBV viral load, and virus-capsid antigen IgG in cerebrospinal fluid were elevated. We diagnosed him with EBV-associated encephalopathy presenting with NCSE. Administration of levetiracetam, an antiepileptic, improved the consciousness and the abnormal hyperperfusion. This case suggests a new concept of EBV-associated encephalopathy leading to epilepsy, particularly in immunosuppressed patients., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)
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- 2020
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36. Phase I/II study of bortezomib, lenalidomide, and dexamethasone treatment for relapsed and refractory multiple myeloma.
- Author
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Mori Y, Choi I, Yoshimoto G, Muta T, Yamasaki S, Tanimoto K, Kamimura T, Iwasaki H, Ogawa R, Akashi K, and Miyamoto T
- Subjects
- Humans, Recurrence, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bortezomib administration & dosage, Dexamethasone administration & dosage, Lenalidomide administration & dosage, Multiple Myeloma drug therapy
- Abstract
Use of novel agents, including proteasome inhibitors and immunomodulatory drugs, has markedly improved outcomes in multiple myeloma (MM) patients. However, most MM patients eventually relapse and require salvage treatments. We report herein the result of a phase I/II study, performed from 2014 to 2017 to assess the feasibility and efficacy of a maximum tolerated dose (MTD) of lenalidomide (Len) combined with a fixed dose of once weekly subcutaneous (sc) 1.3 mg/m
2 of bortezomib plus 20 mg of dexamethasone (scVRd regimen) in relapsed/refractory MM patients in the Japanese population. In the phase I part, dose-limiting toxicities were observed in three of six patients treated with 20 mg of Len; the MTD was accordingly defined as 15 mg in our cohort. In the phase II part, the recommended dose of the scVRD regimen showed a 71.4% best overall response rate, with a median overall survival of 14.8 months and a median progression-free survival of 8 months. Severe adverse events (≥ grade 3) were observed in ~ 15% of the patients, indicating the tolerability and efficacy of the regimen. Less prior treatment was associated with higher probability of durable response. This scVRd regimen may thus be a better fit for MM patients in early-stage relapse.- Published
- 2020
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37. Successful allogeneic stem cell transplantation in a case with acute myeloid leukemia and invasive Schizophyllum commune rhinosinusitis.
- Author
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Harada T, Kuriyama T, Nishida R, Yoshimoto G, Mori Y, Imanaga H, Ueno T, Odawara J, Hayashi M, Kato K, Takenaka K, Akashi K, and Miyamoto T
- Subjects
- Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Drug Therapy, Combination, Female, Humans, Invasive Fungal Infections diagnosis, Invasive Fungal Infections drug therapy, Invasive Fungal Infections microbiology, Leukemia, Myeloid, Acute complications, Middle Aged, Molecular Diagnostic Techniques, Rhinitis complications, Rhinitis diagnosis, Rhinitis drug therapy, Schizophyllum genetics, Schizophyllum isolation & purification, Sinusitis complications, Sinusitis diagnosis, Sinusitis drug therapy, Transplantation, Homologous, Treatment Outcome, Voriconazole therapeutic use, Hematopoietic Stem Cell Transplantation methods, Invasive Fungal Infections complications, Leukemia, Myeloid, Acute therapy, Rhinitis microbiology, Schizophyllum pathogenicity, Sinusitis microbiology
- Abstract
Schizophyllum commune, a basidiomycete fungus, is a quite rare cause of invasive sinusitis for which no standard treatment has yet been established. We report herein a 59-year-old woman who developed S. commune rhinosinusitis after remission induction chemotherapy for her acute myeloid leukemia. No causative microorganisms were identified in the sinus lavage fluid culture, whereas nucleotide sequencing of the internal transcribed spacer region using endoscopic sinus biopsy specimen could confirm the pathogen as S. commune. Liposomal amphotericin B and voriconazole (VRCZ) treatment ameliorated both her clinical symptoms and laboratory findings. The patient was successfully treated with allogeneic stem cell transplantation, under continuous VRCZ administration, without aggravation of S. commune sinusitis. Molecular diagnosis and prompt intervention with suitable antifungal drugs may be crucial to manage this rare infectious complication., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2020
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38. Comparison of calcineurin inhibitors in combination with conventional methotrexate, reduced methotrexate, or mycophenolate mofetil for prophylaxis of graft-versus-host disease after umbilical cord blood transplantation.
- Author
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Yoshida S, Ohno Y, Nagafuji K, Yoshimoto G, Sugio T, Kamimura T, Ohta T, Takase K, Henzan H, Muta T, Iwasaki H, Ogawa R, Eto T, Akashi K, and Miyamoto T
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Calcineurin Inhibitors administration & dosage, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Graft Survival, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Hematologic Neoplasms therapy, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, Incidence, Infections epidemiology, Infections etiology, Japan epidemiology, Kaplan-Meier Estimate, Leukocyte Count, Male, Methotrexate administration & dosage, Methotrexate adverse effects, Middle Aged, Mycophenolic Acid administration & dosage, Neutrophils, Platelet Count, Retrospective Studies, Treatment Outcome, Young Adult, Calcineurin Inhibitors therapeutic use, Cord Blood Stem Cell Transplantation adverse effects, Graft vs Host Disease prevention & control, Immunosuppressive Agents therapeutic use, Methotrexate therapeutic use, Mycophenolic Acid therapeutic use
- Abstract
Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m
2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.- Published
- 2019
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39. Successful rescue transplantation with desensitization procedure after primary graft failure due to donor-specific antibody.
- Author
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Minami M, Matsushima T, Mori Y, Ishihara D, Jinnnouchi F, Takenaka K, Henzan T, Yoshimoto G, Numata A, Kato K, Maeda T, Miyamoto T, and Akashi K
- Subjects
- Humans, Male, Middle Aged, Antibodies immunology, Graft Rejection immunology, HLA Antigens immunology
- Published
- 2019
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40. Adult T-Cell Leukemia After Deceased Donor Liver Transplantation for Acute Liver Failure: A Case Report.
- Author
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Motomura T, Yoshizumi T, Kosai-Fujimoto Y, Mano Y, Toshima T, Takeishi K, Itoh S, Harada N, Ikegami T, Soejima Y, Yoshimoto G, Akashi K, and Mori M
- Subjects
- Hepatitis B complications, Hepatitis B virology, Humans, Immunosuppression Therapy methods, Liver Failure, Acute virology, Liver Transplantation methods, Male, Middle Aged, Hepatitis B surgery, Human T-lymphotropic virus 1, Leukemia-Lymphoma, Adult T-Cell virology, Liver Failure, Acute surgery, Liver Transplantation adverse effects, Postoperative Complications virology
- Abstract
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL); however, the mechanism of its development has yet to be uncovered. A few ATL cases have been reported in HTLV-1-positive recipients after living donor liver transplantation. A 57-year-old HTLV-1-positive Japanese male suffered acute liver failure due to hepatitis B infection. He was transferred to our department to undergo deceased donor liver transplantation (DDLT). Tacrolimus and mycophenolate mofetil were induced for immunosuppression. His clinical outcome was satisfactory. However, he visited his physician 3 years after DDLT reporting abdominal pain and fever. A computed tomography scan showed multiple lymph node enlargement. Lymph node biopsy and his blood sample led to a diagnosis of ATL. He was transferred to the Department of Hematology and Oncology and underwent chemotherapy. To our knowledge, this is the first report of ATL development after DDLT from an HTLV-1-positive recipient. As is the case with our previous report, the current patient had undergone liver transplant for acute liver failure. Unlike living donor liver transplantation, however, DDLT needs no hepatic growth factor for liver regeneration. This finding sheds light on the resolution of the mechanism for the development of ATL from the HTLV-1 carrier., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
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41. Previous exposure to bortezomib is linked to a lower risk of engraftment syndrome after autologous hematopoietic stem cell transplantation.
- Author
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Mori Y, Yoshimoto G, Yuda JI, Hayashi M, Odawara J, Kuriyama T, Sugio T, Miyawaki K, Kamezaki K, Kato K, Takenaka K, Iwasaki H, Maeda T, Miyamoto T, and Akashi K
- Subjects
- Adult, Aged, Female, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Risk Factors, Transplantation, Autologous adverse effects, Young Adult, Bortezomib therapeutic use, Graft vs Host Disease epidemiology, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Published
- 2019
- Full Text
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42. Risk of secondary primary malignancies in multiple myeloma patients with or without autologous stem cell transplantation.
- Author
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Yamasaki S, Yoshimoto G, Kohno K, Henzan H, Aoki T, Tanimoto K, Sugio Y, Muta T, Kamimura T, Ohno Y, Ogawa R, Eto T, Nagafuji K, Miyamoto T, Akashi K, and Iwasaki H
- Subjects
- Incidence, Lenalidomide therapeutic use, Multiple Myeloma mortality, Multiple Myeloma pathology, Risk Factors, Survival Analysis, Transplantation, Autologous methods, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma secondary, Neoplasms, Second Primary chemically induced, Neoplasms, Second Primary etiology
- Abstract
Outcomes for patients with multiple myeloma (MM) have improved through use of novel treatments, especially lenalidomide combined with autologous stem cell transplantation. However, because of their increased life expectancy, an increased risk of secondary primary malignancies (SPMs) has been observed in MM patients, particularly after lenalidomide maintenance in both transplant-eligible (TE) and transplant-ineligible (TI) patients. To evaluate the incidence and risk factors of developing SPMs, we identified 17 TE-MM and 12 TI-MM patients with SPMs among 211 TE-MM and 280 TI-MM patients, including seven TE-MM and four TI-MM patients with hematological malignancies and ten TE-MM and eight TI-MM patients with non-hematological cancers, respectively. The median follow-up time from diagnosis was > 4 years. Multivariate analysis identified a history of high-dose cyclophosphamide use for peripheral blood stem cell harvest in TE-MM patients and > 65 years of age at diagnosis, or a history of adriamycin, lenalidomide, or thalidomide use in TI-MM patients as independent risk factors for SPMs (P < 0.001). Patients with a history of lenalidomide use had a lower risk of death among both TE-MM (P = 0.0326) and TI-MM (P < 0.001) patients. The survival benefit of receiving lenalidomide outweighed the increased risk of SPMs in both TE-and TI-MM patients.
- Published
- 2019
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43. Human Herpes Virus-6-Associated Encephalitis/Myelitis Mimicking Calcineurin Inhibitor-Induced Pain Syndrome in Allogeneic Stem Cell Transplantation Recipients.
- Author
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Yoshimoto G, Mori Y, Kato K, Shima T, Miyawaki K, Kikushige Y, Kamezaki K, Numata A, Maeda T, Takenaka K, Iwasaki H, Teshima T, Akashi K, and Miyamoto T
- Subjects
- Adolescent, Adult, Female, Humans, Male, Middle Aged, Pain pathology, Young Adult, Calcineurin Inhibitors adverse effects, Encephalitis, Viral etiology, Herpesvirus 6, Human pathogenicity, Pain chemically induced, Stem Cell Transplantation adverse effects, Transplantation, Homologous adverse effects
- Abstract
Human herpes virus-6 (HHV6)-associated myelitis and calcineurin inhibitor-induced pain syndrome (CIPS) are serious complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because these 2 complications cause similar sensory nerve-related symptoms, such as paresthesia, pruritus, and severe pain occurring around the engraftment, it can be difficult to differentially diagnose the 2 conditions. We retrospectively analyzed 435 recipients to distinguish clinical symptoms of these 2 complications. Twenty-four patients (5.5%) developed HHV6-associated encephalitis/myelitis; of these, 11 (2.5%) presented only with myelitis-related symptoms (HHV6-associated myelitis), which was confirmed by the detection of HHV6 DNA, and 8 (1.8%) had CIPS, with undetected HHV6 DNA. All patients with HHV6-associated myelitis or CIPS exhibited similar sensory nerve-related symptoms. Diagnostic images did not provide definite evidence specific for each disease. Symptoms of all patients with CIPS improved after switching to another immunosuppressant. Overall survival rate at 2 years for patients with HHV6-associated encephalitis/myelitis was significantly lower than that of CIPS (13.1% versus 29.2%; P = .049) or that of patients without HHV6-associated encephalitis/myelitis or CIPS (42.4%; P = .036), whereas there was no significant difference among the latter 2 groups (P = .889). The development of HHV6-associated encephalitis/myelitis but not CIPS was significantly associated with poor prognosis. Thus, transplant physicians should be aware that sensory nerve-related symptoms indicate early manifestations that might be correlated with reactivation of HHV6 or CIPS. Therefore, identification of HHV6 DNA is crucial for making a differential diagnosis and immediately starting appropriate treatments for each complication., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2018
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44. Gastrointestinal Graft-versus-Host Disease Is a Risk Factor for Postengraftment Bloodstream Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients.
- Author
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Mori Y, Yoshimoto G, Nishida R, Sugio T, Miyawaki K, Shima T, Nagasaki Y, Miyake N, Harada Y, Kunisaki Y, Kamezaki K, Numata A, Kato K, Shiratsuchi M, Maeda T, Takenaka K, Iwasaki H, Shimono N, Akashi K, and Miyamoto T
- Subjects
- Adolescent, Adult, Aged, Bacteremia pathology, Female, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Humans, Male, Middle Aged, Risk Factors, Young Adult, Bacteremia etiology, Gastrointestinal Tract pathology, Graft vs Host Disease complications, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
Bloodstream infection (BSI) is a well-known cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we conducted a retrospective study to assess the morbidity, etiology, risk factors, and outcomes of BSI in the postengraftment period (PE-BSI) after allo-HSCT. Forty-three of 316 patients (13.6%) developed 57 PE-BSI episodes, in which 62 pathogens were isolated: Gram-positive bacteria, gram-negative bacteria, and fungi, respectively, accounted for 54.8%, 35.5%, and 9.7% of the isolates. Multivariate analysis revealed methylprednisolone use for graft-versus-host disease (GVHD) prophylaxis (odds ratio [OR], 6.49; 95% confidence interval [CI], 1.49 to 28.2; P = .013) and acute gastrointestinal GVHD (GI-GVHD) (OR, 8.82; 95% CI, 3.99 to 19.5; P < .0001) as risk factors for developing PE-BSI. This finding suggested that GI-GVHD increases the risk of bacterial translocation and subsequent septicemia. Moreover, among patients with GI-GVHD, insufficient response to corticosteroids, presumably related to an intestinal dysbiosis, significantly correlated with this complication. Patients with PE-BSI presented worse outcome compared with those without (3-year overall survival, 47.0% versus 18.6%; P < .001). Close microbiologic monitoring for BSIs and minimizing intestinal dysbiosis may be crucial to break the vicious cycle between GI-GVHD and bacteremia and to improve transplant outcomes especially in patients who require additional immunosuppressants., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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45. Successful treatment of Ph ALL with hematopoietic stem cell transplantation from the same HLA-haploidentical related donor of previous liver transplantation.
- Author
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Sasaki K, Mori Y, Yoshimoto G, Sakoda T, Kato K, Inadomi K, Kamezaki K, Takenaka K, Iwasaki H, Maeda T, Miyamoto T, and Akashi K
- Subjects
- Histocompatibility Testing, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Transplantation, Homologous, Treatment Outcome, Blood Donors, Hematopoietic Stem Cell Transplantation methods, Liver Transplantation methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Published
- 2018
- Full Text
- View/download PDF
46. Comparative Quantification of Chemotherapy-Induced Nausea and Emesis between the Common Terminology Criteria for Adverse Events and the Multinational Association of Supportive Care in Cancer Antiemesis Tool.
- Author
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Uchida M, Nakamura T, Shima T, Yoshimoto G, Kato K, Hosohata K, Miyamoto T, and Akashi K
- Subjects
- Adult, Aged, Antiemetics therapeutic use, Female, Hospitals, Humans, Japan, Male, Middle Aged, Nausea prevention & control, Vomiting prevention & control, Young Adult, Antineoplastic Agents adverse effects, Hematologic Neoplasms drug therapy, Nausea chemically induced, Severity of Illness Index, Surveys and Questionnaires, Vomiting chemically induced
- Abstract
Chemotherapy-induced nausea and vomiting (CINV) are generally evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). The Multinational Association for Supportive Care in Cancer (MASCC) developed the MASCC Antiemesis Tool (MAT) to facilitate recognition for CINV between patients and oncology specialists. In the present study, MAT and CTCAE were comparatively assessed in Japanese patients with hematological malignancies. A total of 61 patients were eligible for this study. The CTCAE data were collected from an electronic medical record system. The patients were asked to complete the Japanese version of MAT in the hospital, on the first and fourth days after the start of chemotherapy. The percentages of patients in whom nausea was completely controlled, with severity scores of zero, ranged from 70.5 to 82.0% for CTCAE and from 59.0 to 75.4% for MAT, during the first five days after the chemotherapy. The percentages of patients who had no vomiting ranged from 93.4 to 96.7% for CTCAE and from 90.2 to 98.4% for MAT. During the observation periods, the day-to-day response profiles of patients who received antiemetic treatment were comparable between CTCAE and MAT cohorts, and these two assessment tools showed good, positive correlations for nausea severity scores. The present study shows that the MAT is a useful tool for assessing the severity of CINV in patients with hematological malignancy, is comparable to CTCAE, and facilitates the identification of poor cancer care conditions by medical staff.
- Published
- 2018
- Full Text
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47. Recurrent Subcutaneous Sweet's Disease in a Myelofibrosis Patient Treated with Ruxolitinib before Allogeneic Stem Cell Transplantation.
- Author
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Sakoda T, Kanamitsu Y, Mori Y, Sasaki K, Yonemitsu E, Nagae K, Yoshimoto G, Kamezaki K, Kato K, Takenaka K, Miyamoto T, Furue M, Iwasaki H, and Akashi K
- Subjects
- Aged, Chronic Disease, Glucocorticoids therapeutic use, Hematopoietic Stem Cell Transplantation methods, Humans, Male, Nitriles, Pyrazoles adverse effects, Pyrimidines, Sweet Syndrome drug therapy, Primary Myelofibrosis complications, Primary Myelofibrosis drug therapy, Pyrazoles therapeutic use, Sweet Syndrome complications
- Abstract
Allogeneic hematopoietic stem cell transplantation (allo-SCT) has a curative potential for myelofibrosis (MF) patients; however, its association with a high therapy-related mortality (TRM) remains a big obstacle that needs to be overcome. Ruxolitinib (RUXO), a novel JAK1/2 inhibitor, can be used as a bridging therapy until allo-SCT can be performed to reduce TRM. We herein report a RUXO-treated MF patient who developed recurrent subcutaneous Sweet's disease (SSD) that was successfully treated by the administration of systemic glucocorticoids. We performed allo-SCT as previously scheduled, resulting in a good clinical course without deterioration of SSD. RUXO administration, as well as MF itself, might therefore sometimes cause this rare non-infectious event.
- Published
- 2017
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48. Phase I study of glasdegib (PF-04449913), an oral smoothened inhibitor, in Japanese patients with select hematologic malignancies.
- Author
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Minami Y, Minami H, Miyamoto T, Yoshimoto G, Kobayashi Y, Munakata W, Onishi Y, Kobayashi M, Ikuta M, Chan G, Woolfson A, Ono C, Shaik MN, Fujii Y, Zheng X, and Naoe T
- Subjects
- Administration, Oral, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacology, Benzimidazoles adverse effects, Benzimidazoles pharmacology, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Gene Expression Regulation, Neoplastic drug effects, Hematologic Neoplasms genetics, Humans, Japan, Male, Maximum Tolerated Dose, Middle Aged, Phenylurea Compounds adverse effects, Phenylurea Compounds pharmacology, Treatment Outcome, Antineoplastic Agents administration & dosage, Benzimidazoles administration & dosage, Hematologic Neoplasms drug therapy, Phenylurea Compounds administration & dosage, Zinc Finger Protein GLI1 genetics
- Abstract
The hedgehog signaling pathway regulates multiple morphogenetic processes during embryogenesis. Aberrant activation of the hedgehog pathway signal transduction in adult tissues is associated with the pathogenesis of hematologic malignancies and solid tumors. We report findings from an open-label, multicenter phase I trial of the selective, small-molecule hedgehog signaling inhibitor glasdegib (PF-04449913) in Japanese patients with select advanced hematologic malignancies. Glasdegib was administered as once-daily oral doses (25, 50 and 100 mg) in 28-day cycles after a lead-in dose on Day -5. The primary objectives were to determine first-cycle dose-limiting toxicities, safety, vital signs and laboratory test abnormalities. Secondary objectives included evaluation of pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity of glasdegib. No dose-limiting toxicities were noted in the 13 patients in the present study. All patients experienced at least one treatment-emergent, all-causality adverse event. The most frequent treatment-related adverse events (observed in ≥3 patients) were dysgeusia (n = 9), muscle spasms (n = 5), alopecia, decreased appetite (n = 4 each), and increased blood creatinine phosphokinase, constipation and diarrhea (n = 3 each). Two deaths occurred during the study and were deemed not to be treatment-related due to disease progression. Glasdegib demonstrated dose-proportional pharmacokinetics, marked downregulation of the glioma-associated transcriptional regulator GLI1 expression in normal skin, and evidence of preliminary clinical activity, although data are limited. Glasdegib was safe and well tolerated across the dose levels tested. It is confirmed that the 100-mg dose is safe and tolerable in Japanese patients, and this dose level will be examined in the future clinical trial., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2017
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49. Methotrexate-Related Lymphoproliferative Disorder Presenting with Severe Swelling of the Elbow Joint: A Case Report.
- Author
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Hatano T, Ohishi M, Yoshimoto G, Yamauchi M, Maekawa A, Yamamoto H, Oda Y, Endo M, Bekki H, Matsunobu T, Nakashima Y, Okazaki K, Fukushi JI, Oyamada A, and Iwamoto Y
- Subjects
- Antirheumatic Agents administration & dosage, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid complications, Elbow Joint diagnostic imaging, Female, Humans, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoproliferative Disorders diagnosis, Magnetic Resonance Imaging methods, Methotrexate administration & dosage, Methotrexate therapeutic use, Middle Aged, Patient Outcome Assessment, Positron-Emission Tomography methods, Tomography, X-Ray Computed methods, Antirheumatic Agents adverse effects, Arthritis, Rheumatoid drug therapy, Elbow Joint pathology, Lymphoma, Large B-Cell, Diffuse chemically induced, Lymphoproliferative Disorders chemically induced, Methotrexate adverse effects
- Abstract
Case: A patient with rheumatoid arthritis (RA) who was being treated with methotrexate (MTX) therapy presented with severe swelling of the left elbow. Magnetic resonance imaging showed a tumor-like lesion around the elbow joint. Fluorodeoxyglucose positron emission tomography indicated multiple lesions in the lung and the lymph nodes. An open biopsy of a cervical lymph node was performed, and MTX-related lymphoproliferative disorder (MTX-LPD) was diagnosed. After cessation of the MTX therapy, the elbow swelling regressed, and the patient was in remission of MTX-LPD., Conclusion: MTX-LPD should be considered in the differential diagnosis when a patient with RA develops severe joint swelling while on MTX therapy.
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- 2017
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50. Mobilization of human immature hematopoietic progenitors through combinatory use of bortezomib and immunomodulatory drugs.
- Author
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Tochigi T, Aoki T, Kikushige Y, Kamimura T, Ito Y, Shima T, Yamauchi T, Mori Y, Yoshimoto G, Kamezaki K, Kato K, Takenaka K, Iwasaki H, Akashi K, and Miyamoto T
- Subjects
- Aged, Antigens, CD34 drug effects, Blood Cells drug effects, Bone Marrow Cells drug effects, Bortezomib therapeutic use, Dexamethasone adverse effects, Dexamethasone therapeutic use, Drug Therapy, Combination, Female, Humans, Immunologic Factors therapeutic use, Lenalidomide, Male, Middle Aged, Multiple Myeloma drug therapy, Receptors, CXCR4 drug effects, Thalidomide adverse effects, Thalidomide analogs & derivatives, Thalidomide therapeutic use, Bortezomib adverse effects, Hematopoietic Stem Cell Mobilization methods, Hematopoietic Stem Cells drug effects, Immunologic Factors adverse effects
- Abstract
Combination use of the proteasome inhibitor bortezomib and the immunomodulatory drugs lenalidomide or thalidomide has provided superior outcomes in multiple myeloma over their single use; however, these combinations can produce significant toxicities. Unexpectedly, we found a small but significant increase in the population of immature granulocytes and erythrocytes/megakaryocytes in peripheral blood in 16 of 22 patients (73%) treated with dexamethasone in combination with bortezomib and immunomodulatory drugs (triplet), but not in any of 25 patients treated with either bortezomib or immunomodulatory drugs with dexamethasone (doublet). These immature cells gradually increased to a peak level (mean 2.6% per white blood cells) with triplet therapy, and disappeared immediately after therapy cessation. The numbers of circulating CD34
+ cells and colony-forming cells derived from peripheral blood mononuclear cells increased after triplet therapy compared with those in patients treated by either bortezomib or immunomodulatory drugs plus dexamethasone. Furthermore, triplet regimen downregulated the expression of CXCR4, a chemokine receptor essential for bone marrow retention, on CD34+ cells, suggesting an unexpected effect on normal hematopoietic stem/progenitor cells through the reduced interaction with the bone marrow microenvironment. Our observations suggest that combination use should be carefully evaluated to exert synergistic anti-myeloma effects while avoiding unexpected adverse events.- Published
- 2017
- Full Text
- View/download PDF
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