31 results on '"Kyoko Yoshihara"'
Search Results
2. Severe acute heart failure during or following cytokine release syndrome after CAR T-cell therapy
- Author
-
Kyoko Yoshihara, Yoshiyuki Orihara, Tokiko Hoshiyama, Hiroya Tamaki, Isamu Sunayama, Ikuo Matsuda, Akinori Nishikawa, Tomoko Kumamoto, Mami Samori, Nobuto Utsunomiya, Kyung-Duk Min, Masanori Asakura, Seiichi Hirota, Masaharu Ishihara, Satoshi Higasa, and Satoshi Yoshihara
- Subjects
Cytokine release syndrome ,Acute heart failure ,CAR T-cell therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Although cardiac dysfunction after chimeric antigen receptor (CAR) T-cell therapy has been increasingly reported, the underlying dynamics and pathogenesis are not well documented. Herein, we describe the clinical presentation and treatment for two patients who developed severe acute heart failure after CAR T-cell therapy. Both cases shared several common characteristics, including the bone marrow involvement at the time of CAR T-cell therapy and early onset of cytokine release syndrome (CRS) with fever developing on the day of CAR T-cell infusion. Patients with early onset and/or severe CRS should be carefully monitored for the possibility of heart failure.
- Published
- 2022
- Full Text
- View/download PDF
3. High Prevalence of PNH-phenotype Cells in Patients Who Received CD19-targeted CAR T-cell Therapy
- Author
-
Kyoko Yoshihara, Ikuo Matsuda, Nobuto Utsunomiya, Mami Samori, Saki Hirata, Masaya Okada, Seiichi Hirota, Satoshi Higasa, and Satoshi Yoshihara
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2021
- Full Text
- View/download PDF
4. ESTABLISHMENT OF A SUSTAINABLE CAR T-CELL THERAPY OPERATION SYSTEM BY UTILIZING THE ALREADY-EXISTING STRUCTURE AT THE BLOOD TRANSFUSION DIVISION
- Author
-
Junko Ikemoto, Satoshi Yoshihara, Izumi Yamashita, Mao Tsujimoto, Fuka Yamaguchi, Yuki Harada, Hiroki Sugiyama, Shinya Otsuka, Rie Murata, Hitomi Onomoto, Noriko Okuda, Risa Takao, Asuka Ikegami, Mari Suita, Ayaka Uemura, Mariko Kawaguchi, Kyoko Yoshihara, Kenichi Yamahara, and Satoshi Higasa
- Subjects
Cultural Studies ,Education - Published
- 2022
5. Early evaluation of CAR-T cell therapy response in R/R 18 DLBCLpatients using F-FDG PET/CT.
- Author
-
Kazuhiro Kitajima, Hiroyuki Yokoyama, Reona Wada, Yukihisa Tamaki, Kyoko Yoshihara, Katsuji Kaida, Satoshi Yoshihara, and Koichiro Yamakado
- Published
- 2024
6. Association between the pharmacokinetics of rabbit anti-thymocyte globulin and acute graft-versus-host disease in patients who received haploidentical hematopoietic stem cell transplantation
- Author
-
Masahiro Teramoto, Satoshi Maruyama, Hiroya Tamaki, Katsuji Kaida, Azusa Mayumi, Keiko Fukunaga, Takayuki Inoue, Kyoko Yoshihara, Satoshi Yoshihara, Kazuhiro Ikegame, Masaya Okada, Yuko Osugi, Hiroyasu Ogawa, Satoshi Higasa, Kunihiko Morita, Kana Matsumoto, and Takashi Kijima
- Subjects
Transplantation Conditioning ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Hematology ,Antilymphocyte Serum ,Retrospective Studies - Abstract
Anti-thymocyte globulin (ATG) is an important prophylactic drug against acute graft-versus-host disease (aGVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study analyzed the pharmacokinetics of rabbit ATG 2.5 mg/kg and its effect against aGVHD in 24 patients undergoing unmanipulated haplo-HSCT. All patients had hematological malignancies not in remission. The median absolute lymphocyte count (ALC) before rabbit ATG administration was 9.5/µL (range 0-41/µL). The grade ≥ II aGVHD group had a significantly lower median rabbit ATG concentration on days 0 (C
- Published
- 2022
7. FALSE-POSITIVE RESULTS IN AN IRREGULAR ANTIBODY SCREENING TEST AFTER MEASURING SAMPLES FROM A PATIENT RECEIVING ANTI-CD38 MONOCLONAL ANTIBODY USING AN AUTOMATED PRE-TRANSFUSION TESTING SYSTEM
- Author
-
Shinya Otsuka, Junko Ikemoto, Kyoko Yoshihara, Mao Tsujimoto, Fuka Yamaguchi, Yuki Harada, Hiroki Sugiyama, Hitomi Onomoto, Rie Murata, Noriko Okuda, Kenichi Yamahara, Satoshi Higasa, and Satoshi Yoshihara
- Published
- 2021
8. T‐cell lymphoma, B‐cell lymphoma, and myelodysplastic syndrome harboring common mutations: Trilineage tumorigenesis from a common founder clone
- Author
-
Kyoko Yoshihara, Yasuhito Nannya, Ikuo Matsuda, Mami Samori, Nobuto Utsunomiya, Masaya Okada, Seiichi Hirota, Seishi Ogawa, and Satoshi Yoshihara
- Published
- 2021
9. Measurable Residual Disease Assessment Using Next-Generation Flow in Patients With Relapsed and Refractory Multiple Myeloma Treated With a Combination of Carfilzomib, Lenalidomide, and Dexamethasone
- Author
-
TAKESHI YOROIDAKA, TAKESHI YAMASHITA, RYOICHI MURATA, KYOKO YOSHIHARA, SATOSHI YOSHIHARA, MIKIO UEDA, SHINJI NAKAO, KOSEI MATSUE, and HIROYUKI TAKAMATSU
- Subjects
Cancer Research ,Neoplasm, Residual ,Oncology ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,General Medicine ,Prospective Studies ,Neoplasm Recurrence, Local ,Multiple Myeloma ,Lenalidomide ,Dexamethasone - Abstract
Carfilzomib, lenalidomide, and dexamethasone (KRD) therapy is widely used for patients with relapse/refractory multiple myeloma (RRMM). However, the response in patients who underwent assessment for measurable residual disease (MRD) has not been elucidated in a prospective study. We aimed to clarify the response rate and outcome of KRD therapy in patients in RRMM, including those with MRD.Twenty-one consecutive RRMM patients treated with KRD at 4 Japanese Centers between September 2016 and October 2018 were enrolled and assessed for MRD in the bone marrow (cut-off: 1×10The median number of therapy lines before KRD was 3 (range=1-6), and the median number of KRD cycles was 4 (range=1-22). As the best overall response post-KRD therapy, 52% (11/21) of patients achieved a MRD negative complete response, 71% (15/21) achieved stringent complete response/complete response, and 14% (3/21) achieved a very good partial response. MRD negativity was achieved in 12 of 16 (75%) and 14 of 21 (67%) patients during and after KRD treatment, respectively. The 2-year progression-free survival and overall survival from the start of KRD therapy were 100% and 100%, respectively, in MRD-positive cases and 88% and 100%, respectively, in MRD-negative cases (median follow-up=1.8 years). Grade 3/4 toxicities were reported in 15 patients (71%), with thrombocytopenia being the most frequent toxicity (6 patients, 29%).This is the first study that prospectively assessed MRD of patients with RRMM after KRD therapy. KRD treatment achieved a high MRD negativity rate and good outcomes with manageable toxicities.
- Published
- 2022
10. Impact of the use of hydroxyethyl starch in granulocyte apheresis using Spectra Optia
- Author
-
Katsuji Kaida, Yuko Osugi, Satoshi Higasa, Keiko Fukunaga, Kenichi Yamahara, Hiroya Tamaki, Kazuhiro Ikegame, Junko Ikemoto, Masaya Okada, Hitomi Onomoto, Satoshi Yoshihara, Kyoko Yoshihara, Hiroki Sugiyama, Yoshihiro Fujimori, and Noriko Okuda
- Subjects
medicine.medical_specialty ,Renal function ,030204 cardiovascular system & hematology ,Hydroxyethyl starch ,Granulocyte ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Adverse effect ,reproductive and urinary physiology ,Retrospective Studies ,business.industry ,Potential risk ,Starch ,Hematology ,Leukocyte Transfusion ,Apheresis ,medicine.anatomical_structure ,Blood Component Removal ,Absolute neutrophil count ,biological phenomena, cell phenomena, and immunity ,business ,Granulocytes ,030215 immunology ,medicine.drug - Abstract
OBJECTIVES To determine the impact of the use of hydroxyethyl starch (HES) in granulocyte apheresis using Spectra Optia. BACKGROUND Granulocyte transfusion (GT) is a therapeutic option for neutropenic patients with severe bacterial or fungal infections. Recent studies in emergency medicine have shown the potential risk of using HES, which is routinely used in granulocyte apheresis to increase yield by sedimenting red blood cells. We hypothesized that the use of a newer device (Spectra Optia) would spare the need for HES. METHODS We retrospectively compared granulocyte apheresis with HES (HES group, n = 89) and without HES (non-HES group, n = 36) using Spectra Optia. RESULTS The granulocyte yield was significantly higher in the HES group (7.3 × 1010 vs. 2.0 × 10, p
- Published
- 2021
11. Feasibility of six cycles of lenalidomide-based triplet induction before stem cell collection for newly diagnosed transplant-eligible multiple myeloma
- Author
-
Yoshifumi Shimizu, Masaya Okada, Hiroyuki Kawamoto, Mahito Misawa, Hideki Ifuku, Takehito Imado, Hiroyuki Takatsuka, Yoshihiro Fujimori, Satoshi Yoshihara, Yokiko Ohe, and Kyoko Yoshihara
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Stem Cell Collection ,Dexamethasone ,Bortezomib ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Autologous stem-cell transplantation ,Induction therapy ,Internal medicine ,Humans ,Medicine ,Prospective Studies ,Lenalidomide ,Multiple myeloma ,Aged ,business.industry ,Induction Chemotherapy ,Hematology ,Middle Aged ,medicine.disease ,Carfilzomib ,Minimal residual disease ,Hematopoietic Stem Cell Mobilization ,chemistry ,030220 oncology & carcinogenesis ,Feasibility Studies ,Female ,Multiple Myeloma ,business ,030215 immunology ,medicine.drug - Abstract
Achieving a deep response with induction therapy has a major impact on outcomes following autologous stem cell transplantation. Although longer and intensified induction therapy may provide better disease control, longer exposure to lenalidomide negatively affects stem cell yield. We examined the feasibility of 6 cycles of lenalidomide-based triplet induction therapy before stem cell collection in transplant-eligible multiple myeloma patients.In this prospective study, patients received a combination of bortezomib, lenalidomide, and dexamethasone for 6 cycles. For patients who did not achieve a deep response after 3 cycles, bortezomib was substituted with carfilzomib for the last 2 cycles (5th and 6th courses).Although only half of the patients achieved a deep response after 3 cycles, all but 1 patient achieved a very good partial response (This study demonstrates that 6 cycles of lenalidomide-based induction therapy before stem cell collection are a feasible and promising approach for transplant-eligible newly diagnosed multiple myeloma patients.The study is registered at UMIN Clinical Trials Registry as UMIN000026936.
- Published
- 2021
12. Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study
- Author
-
Shinichi Ishii, Satoshi Fujino, Keiko Fukunaga, Yosihiro Fujimori, Hiroya Tamaki, Satoshi Maruyama, Masaya Okada, Takayuki Inoue, Yuko Osugi, Katsuji Kaida, Kazuhiro Ikegame, Masahiro Teramoto, Hiroyasu Ogawa, Takaya Yamashita, Azusa Mayumi, Kyoko Yoshihara, and Satoshi Yoshihara
- Subjects
Oncology ,Melphalan ,Transplantation ,medicine.medical_specialty ,Neutrophil Engraftment ,business.industry ,medicine.medical_treatment ,Hematology ,Hematopoietic stem cell transplantation ,Total body irradiation ,Tacrolimus ,Fludarabine ,03 medical and health sciences ,surgical procedures, operative ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Cytarabine ,business ,030215 immunology ,medicine.drug - Abstract
HLA haploidentical hematopoietic stem cell transplantation (HSCT), i.e., HSCT from a 1-HLA-haplotype-mismatched family donor, has been successfully performed even as a second transplantation for posttransplant relapse. Is the haploidentical the limit of HLA mismatches in HSCT? In order to explore the possibility of HLA-mismatched HSCT from family donors beyond haploidentical relatives, we conducted a prospective phase I/II study of 2-HLA-haplotype-mismatched HSCT (2-haplo-mismatch HSCT). We enrolled 30 patients with posttransplant relapse (acute myeloid leukemia: 18, acute lymphoblastic leukemia: 11, non-Hodgkin lymphoma: 1). 2-haplo-mismatch HSCT was performed as the second to sixth transplantations. The donors were siblings (n = 12), cousins (n = 16), and second cousins (n = 2). The conditioning regimen consisted of fludarabine, cytarabine, melphalan, low-dose anti-thymocyte globulin, and 3 Gy of total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. All patients achieved neutrophil engraftment, except for a case of early death. The cumulative incidences of grades II–IV and III–IV acute GVHD were 36.7% and 16.7%, respectively. The overall survival at 1 year, relapse, and non-relapse mortality rates was 30.1%, 38.9%, and 44.3%, respectively. Considering the poor prognosis of posttransplant relapse, 2-haplo-mismatch HSCT can be an alternative option in a second or third transplantation.
- Published
- 2020
13. Abstract 10168: Association Between the Grade of Cytokine Release Syndrome and Cardiac Dysfunction After Chimeric Antigen Receptor T Cell Therapy for Diffuse Large B Cell Lymphoma Patients
- Author
-
Isamu Sunayama, Yoshiyuki Orihara, Kyung-duk Min, Satoshi Yoshihara, Kyoko Yoshihara, Yuki Matsumoto, Koichi Nishimura, Tetsuo Horimatsu, Yoshiro Naito, Akiko Goda, Hiroya Tamaki, Satoshi Higasa, Masanori Asakura, and Masaharu Ishihara
- Subjects
Physiology (medical) ,otorhinolaryngologic diseases ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: As Chimeric Antigen Receptor T cell (CAR-T) therapy gains its clinical advantage in the management of diffuse large B cell lymphoma (DLBCL), accumulating evidence shows that it often accompanies cardiac dysfunction. Previous retrospective studies indicated the involvement of cytokine release syndrome (CRS) in cardiac dysfunction after CAR-T therapy, but their association is not fully investigated. Therefore, we designed a prospective study to clarify the association between the grade of CRS and cardiac dysfunction in the DLBCL patients after CAR-T therapy. Methods: In this prospective study, 14 DLBCL patients who underwent CAR-T therapy from July 2020 to May 2021 were enrolled. Before and after CAR-T therapy, we collected the levels of troponin T (TnT) as a marker for myocardial damage, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) as markers for systolic function, and E/e’ and left atrial volume index (LAVI) as markers for diastolic function. We classified all patients into two groups according to the severity of CRS after CAR-T therapy, namely the low-CRS Group (CRS Results: Average age was 56.4 years and 7 patients (50%) were female. The number of patients in the low-CRS and high-CRS Group were 11 and 3, respectively. Before CAR-T therapy, there were no differences in cardiac function between the two groups. From the hyper-early phase of CAR-T therapy, the increase of TnT, E/e’ and LAVI from the baseline were significantly larger in the high-CRS Group compared to the low-CRS Group (P=0.023, 0.039, and 0.024, respectively). Subsequently, the decrease of GLS from the baseline became significantly larger in the high-CRS Group compared to the low-CRS Group (P=0.049). These results indicated that cardiac dysfunction after CAR-T therapy occurred in the order of myocardial damage, diastolic dysfunction, and systolic dysfunction. Conclusion: We for the first time demonstrated the association between high-grade CRS and cardiac dysfunction after CAR-T therapy through a prospective study.
- Published
- 2021
14. Relationship between Pharmacokinetics of Rabbit Anti-Thymocyte Globulin and Acute Graft Versus Host Disease in Haploidentical Hematopoietic Stem Cell Transplantation
- Author
-
Masahiro Teramoto, Satoshi Maruyama, Hiroya Tamaki, Katsuji Kaida, Azusa Mayumi, Keiko Fukunaga, Takayuki Inoue, Kyoko Yoshihara, Satoshi Yoshihara, Kazuhiro Ikegame, Masaya Okada, Yuko Osugi, Hiroyasu Ogawa, Kunihiko Morita, Kana Matsumoto, and Satoshi Higasa
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2022
15. Treatment strategy in a patient showing borderline features between plasmablastic lymphoma and plasmablastic myeloma harboring a 17p deletion
- Author
-
Seiichi Hirota, Yoshihiro Fujimori, Yoshifumi Shimizu, Masaya Okada, Kyoko Yoshihara, Satoshi Yoshihara, Takehito Imado, Ikuo Matsuda, and Shohei Matsuo
- Subjects
medicine.medical_specialty ,Pathology ,Hematology ,medicine.diagnostic_test ,17p deletion ,business.industry ,General Medicine ,Smith–Magenis syndrome ,medicine.disease ,Internal medicine ,Biopsy ,medicine ,Treatment strategy ,Immunohistochemistry ,business ,Plasmablastic lymphoma ,Positron Emission Tomography-Computed Tomography - Published
- 2020
16. Predictive value of interim FDG-PET/CT findings in patients with diffuse large B-cell lymphoma treated with R-CHOP
- Author
-
Junichi Taniguchi, Kazuhiro Kitajima, Syuji Ueda, Hiroyuki Kawamoto, Hiroya Tamaki, Masaya Okada, Yoshihiro Fujimori, Akihiro Sawada, Koichiro Yamakado, Tazuko Tokugawa, Satoshi Yoshihara, and Kyoko Yoshihara
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Vincristine ,PET-CT ,03 medical and health sciences ,0302 clinical medicine ,Prednisone ,Medicine ,Progression-free survival ,medicine.diagnostic_test ,business.industry ,non-Hodgkin lymphoma ,medicine.disease ,Lymphoma ,030104 developmental biology ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Rituximab ,Radiology ,business ,Diffuse large B-cell lymphoma ,progression-free survival ,Research Paper ,medicine.drug - Abstract
Objectives: To examine the prognostic value of interim 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings after 2–4 cycles of rituximab, plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL) receiving standardized treatment. Results: After a median 3.36 years (range 0.33 to 9.14 years), 24 of the 80 patients had documented relapse. In Interim-PET findings, 2-year PFS was significantly shorter for PET-positive as compared with PET-negative patients (50.0% vs. 86.4%; p = 0.0012). In End-PET findings, 2-year PFS was significantly shorter for PET-positive as compared with PET-negative patients (25.0% vs. 84.7%; p < 0.0001). The positive predictive value (PPV) and negative predictive value (NPV) of Interim-PET for predicting relapse or disease progression were 57.1% and 75.8%, respectively, while those for End-PET were 75.0% and 75.0%, respectively. Methods: Eighty DLBCL patients treated with first-line 6–8 R-CHOP courses regardless of interim imaging findings were enrolled. Each underwent FDG-PET/CT scanning at staging, and again during (Interim-PET) and at the end of (End-PET) therapy. PET positivity or negativity at Interim-PET and End-PET as related to progression-free survival (PFS) was examined using Kaplan–Meier analysis. Conclusion: Mid-treatment FDG-PET/CT findings may be useful for determining disease status in patients with DLBCL undergoing induction R-CHOP chemotherapy, though are not recommended for treatment decisions as part of routine clinical practice.
- Published
- 2019
17. Early evaluation of tumor response to 90Y-ibritumomab radioimmunotherapy in relapsed/refractory B cell non-Hodgkin lymphoma: what is the optimal timing for FDG-PET/CT?
- Author
-
Tazuko Tokugawa, Yoshihiro Fujimori, Satoshi Yoshihara, Masaya Okada, Koichiro Yamakado, Toru Kashiwagi, Kazuhiro Kitajima, Kyoko Yoshihara, and Akihiro Sawada
- Subjects
Fluorodeoxyglucose ,PET-CT ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Follicular lymphoma ,General Medicine ,Progressive Metabolic Disease ,medicine.disease ,030218 nuclear medicine & medical imaging ,Lymphoma ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Radioimmunotherapy ,medicine ,Radiology, Nuclear Medicine and imaging ,Progression-free survival ,Radiology ,business ,Survival analysis ,medicine.drug - Abstract
To determine the earliest optimal timing for assessment of early response following radioimmunotherapy in non-Hodgkin lymphoma patients using FDG-PET/CT. FDG-PET/CT was performed prior to treatment (PET1), at 2 (PET2) weeks, and at 6 (PET3) weeks after 90Y-ibritumomab radioimmunotherapy in 55 patients. Response was evaluated based on the Deauville 5-point scale and Lugano criteria as well as semiquantitative analysis and compared with progression-free survival (PFS). PET 2 showed complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) in 33, 13, 6, and 3 patients, respectively, while PET 3 in 41, 8, 3, and 3 patients, respectively. Mean SUVmax of 168 target lesions decreased over time (PET1, 2, 3; 5.58 ± 2.58, 1.87 ± 1.78, 1.75 ± 2.25, respectively). Progression or recurrence after a median of 12.6 months (range 2.6–72.0 months) was seen in 44 patients. Patients with CMR or metabolic response (CMR + PMR) on PET2 showed significantly longer PFS as compared to those who did not (p = 0.00028 and p = 0.029, respectively). A similar significant difference was observed based on PET3 (p = 0.00013 and p = 0.017, respectively). The same trend was observed when analyzing only the subgroup of patients with follicular lymphoma (N = 43/55) (p
- Published
- 2019
18. A Clinically Applicable Prediction Model to Improve T Cell Collection in Chimeric Antigen Receptor T Cell Therapy
- Author
-
Tomoyasu Jo, Satoshi Yoshihara, Asuka Hada, Yasuyuki Arai, Toshio Kitawaki, Junko Ikemoto, Hitomi Onomoto, Hiroki Sugiyama, Kyoko Yoshihara, Natsuno Obi, Keiko Matsui, Norimi Niwa, Yoko Nakagawa, Junya Kanda, Tadakazu Kondo, Satoshi Saida, Itaru Kato, Hidefumi Hiramatsu, Souichi Adachi, Junko Takita, Akifumi Takaori-Kondo, and Miki Nagao
- Subjects
Transplantation ,Receptors, Chimeric Antigen ,T-Lymphocytes ,Cell- and Tissue-Based Therapy ,Lymphapheresis ,Cell Biology ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Immunotherapy, Adoptive ,Humans ,Molecular Medicine ,Immunology and Allergy ,CAR T cell therapy ,Collection efficiency - Abstract
As chimeric antigen receptor (CAR) T cell therapy targeting CD19 has shown favorable outcomes in patients with relapsed or refractory (r/r) mature B cell lymphomas and B cell acute lymphoblastic leukemia (B-ALL), an increasing number of patients are waiting to receive these treatments. Optimized protocols for T cell collection by lymphapheresis for chimeric antigen receptor (CAR) T cell therapy are urgently needed to provide CAR T cell therapy for patients with refractory and progressive disease and/or a low number of lymphocytes owing to prior chemotherapy. The predicted efficiency of CD³⁺ cell collection in apheresis can guide protocols for apheresis, but a clinically applicable model to produce reliable estimates has not yet been established. In this study, we prospectively analyzed 108 lymphapheresis procedures for tisagenlecleucel therapy at 2 centers. The apheresis procedures included 20 procedures in patients with B cell acute lymphoblastic leukemia and 88 procedures in patients with diffuse large B cell lymphoma, with a median age at apheresis of 58 years (range, 1 to 71 years). After lymphapheresis with a median processing blood volume of 10 L (range, 3 to 16 L), a median of 3.2 × 10⁹ CD³⁺ cells (range, .1 to 15.0 × 10⁹ cells) were harvested. Collection efficiency 2 (CE2) for CD³⁺ cells was highly variable (median, 59.3%; range, 11.0% to 199.8%). Multivariate analyses revealed that lower hemoglobin levels, higher circulating CD3+ cell counts, and higher platelet counts before apheresis significantly decreased apheresis CE2. Based on multivariate analyses, we developed a novel formula that estimates CE2 from precollection parameters with high accuracy (r = .56; P < .01), which also suggests the necessary processing blood volume. Our strategy for lymphapheresis should help reduce collection failure, as well as achieve efficient utilization of medical resources in clinical practice, thereby allowing delivery of CAR T cell therapy to more patients in a timely manner., キメラ抗原受容体T細胞療法におけるリンパ球採取効率化の取り組み --最適な治療戦略策定への貢献に期待--. 京都大学プレスリリース. 2022-06-20.
- Published
- 2022
19. [Clinical experience of leukapheresis for CD19 CAR-T cell therapy]
- Author
-
Tomoyasu, Jo, Satoru, Yoshihara, Yasuyuki, Arai, Junko, Ikemoto, Hitomi, Onomoto, Hiroki, Sugiyama, Kyoko, Yoshihara, Keiko, Matsui, Norimi, Niwa, Yoko, Nakagawa, Toshio, Kitawaki, Junya, Kanda, Akifumi, Takaori-Kondo, and Miki, Nagao
- Subjects
Receptors, Chimeric Antigen ,Antigens, CD19 ,Cell- and Tissue-Based Therapy ,Humans ,Leukapheresis ,Retrospective Studies - Abstract
To perform chimeric antigen receptor T (CAR-T) cell therapy in heavily pretreated patients with progressive disease and depleted lymphocytes, an optimized leukapheresis protocol must be established. To probe the effects of patient-related parameters on the collection efficiency of CD3
- Published
- 2021
20. Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study
- Author
-
Kazuhiro, Ikegame, Katsuji, Kaida, Keiko, Fukunaga, Yuko, Osugi, Kyoko, Yoshihara, Satoshi, Yoshihara, Shinichi, Ishii, Satoshi, Fujino, Takaya, Yamashita, Azusa, Mayumi, Satoshi, Maruyama, Masahiro, Teramoto, Takayuki, Inoue, Masaya, Okada, Hiroya, Tamaki, Hiroyasu, Ogawa, and Yosihiro, Fujimori
- Subjects
Transplantation Conditioning ,Haplotypes ,Recurrence ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Prospective Studies - Abstract
HLA haploidentical hematopoietic stem cell transplantation (HSCT), i.e., HSCT from a 1-HLA-haplotype-mismatched family donor, has been successfully performed even as a second transplantation for posttransplant relapse. Is the haploidentical the limit of HLA mismatches in HSCT? In order to explore the possibility of HLA-mismatched HSCT from family donors beyond haploidentical relatives, we conducted a prospective phase I/II study of 2-HLA-haplotype-mismatched HSCT (2-haplo-mismatch HSCT). We enrolled 30 patients with posttransplant relapse (acute myeloid leukemia: 18, acute lymphoblastic leukemia: 11, non-Hodgkin lymphoma: 1). 2-haplo-mismatch HSCT was performed as the second to sixth transplantations. The donors were siblings (n = 12), cousins (n = 16), and second cousins (n = 2). The conditioning regimen consisted of fludarabine, cytarabine, melphalan, low-dose anti-thymocyte globulin, and 3 Gy of total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. All patients achieved neutrophil engraftment, except for a case of early death. The cumulative incidences of grades II-IV and III-IV acute GVHD were 36.7% and 16.7%, respectively. The overall survival at 1 year, relapse, and non-relapse mortality rates was 30.1%, 38.9%, and 44.3%, respectively. Considering the poor prognosis of posttransplant relapse, 2-haplo-mismatch HSCT can be an alternative option in a second or third transplantation.
- Published
- 2019
21. High Prevalence of PNH-phenotype Cells in Patients Who Received CD19-targeted CAR T-cell Therapy
- Author
-
Satoshi Yoshihara, Satoshi Higasa, Seiichi Hirota, Mami Samori, Kyoko Yoshihara, Nobuto Utsunomiya, Saki Hirata, Masaya Okada, and Ikuo Matsuda
- Subjects
Oncology ,medicine.medical_specialty ,Letter ,High prevalence ,biology ,business.industry ,MEDLINE ,Hematology ,Phenotype ,CD19 ,Internal medicine ,medicine ,biology.protein ,CAR T-cell therapy ,Diseases of the blood and blood-forming organs ,In patient ,RC633-647.5 ,business - Published
- 2021
22. Spousal hematopoietic stem cell transplantation
- Author
-
Hiroh Saji, Satoshi Yoshihara, Yasushi Kusunoki, Hiroto Kojima, Toshihiro Soma, Kyoko Yoshihara, Masaya Okada, Hiroya Tamaki, Takayuki Inoue, Shinichi Ishii, Hiroyasu Ogawa, Kazuhiro Ikegame, and Katsuji Kaida
- Subjects
Adult ,Male ,Melphalan ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,03 medical and health sciences ,Fatal Outcome ,0302 clinical medicine ,HLA Antigens ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Spouses ,Antilymphocyte Serum ,Leukemia ,business.industry ,Hematopoietic Stem Cell Transplantation ,Radiotherapy Dosage ,Hematology ,Middle Aged ,Total body irradiation ,Allografts ,Combined Modality Therapy ,Tacrolimus ,Surgery ,Fludarabine ,Transplantation ,Regimen ,Treatment Outcome ,surgical procedures, operative ,Methylprednisolone ,Histocompatibility ,030220 oncology & carcinogenesis ,Female ,business ,Vidarabine ,030215 immunology ,medicine.drug - Abstract
We report a pilot series of five patients who received stem cell transplantation (SCT) from a spouse for post-transplant relapse or rejection. The inclusion criterion regarding HLA disparities was three or fewer antigen mismatches in the graft-versus-host direction at the HLA-A, B, and DR loci. Four patients received spousal SCT as a third transplant attempt after post-transplant relapse and one as rescue for graft rejection. The reduced intensity conditioning (RIC) regimen consisted of fludarabine, melphalan, and anti-thymocyte globulin (ATG) with 3 Gy of total body irradiation (TBI) for relapse cases and ATG plus 4 Gy of TBI for the rejection case. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. Peripheral blood stem cells were transplanted. Granulocyte engraftment was achieved in all cases between days 9 and 11 (median, 10) with complete spousal chimerism. In three of the five patients, no acute GVHD was observed, while one case developed grade III GVHD and one case grade IV. All four patients evaluable for the anti-leukemic effect achieved complete remission; however, all relapsed between 106 and 334 day post-transplant, and died between days 152 and 548. We suggest that spousal SCT can be performed as a repetitive SCT using a RIC regimen with low-dose ATG and steroid-containing GVHD prophylaxis.
- Published
- 2016
23. Early evaluation of tumor response to
- Author
-
Kazuhiro, Kitajima, Masaya, Okada, Toru, Kashiwagi, Kyoko, Yoshihara, Tazuko, Tokugawa, Akihiro, Sawada, Satoshi, Yoshihara, Yoshihiro, Fujimori, and Koichiro, Yamakado
- Subjects
Adult ,Aged, 80 and over ,Male ,B-Lymphocytes ,Lymphoma, B-Cell ,Antibodies, Monoclonal ,Middle Aged ,Radioimmunotherapy ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,Disease Progression ,Humans ,Female ,Prospective Studies ,Neoplasm Recurrence, Local ,Radionuclide Imaging ,Aged - Abstract
To determine the earliest optimal timing for assessment of early response following radioimmunotherapy in non-Hodgkin lymphoma patients using FDG-PET/CT.FDG-PET/CT was performed prior to treatment (PET1), at 2 (PET2) weeks, and at 6 (PET3) weeks afterPET 2 showed complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) in 33, 13, 6, and 3 patients, respectively, while PET 3 in 41, 8, 3, and 3 patients, respectively. Mean SUVUse of FDG-PET/CT findings with Lugano criteria for assessing early response to radioimmunotherapy after 6 weeks allowed for accurate evaluation and prognostic stratification, though scanning after 2 weeks was too soon to precisely evaluate response.• The optimal timing of FDG-PET/CT to obtain a suitable tool for assessment of response after
- Published
- 2018
24. Minimal Residual Disease Assessment Using Euroflow-NGF in Patients with Multiple Myeloma Treated with a Combination of Carfilzomib, Lenalidomide, and Dexamethasone (KRD)
- Author
-
Takeshi Yamashita, Mikio Ueda, Hiroyuki Takamatsu, Shinji Nakao, Ryoichi Murata, Takeshi Yoroidaka, Kyoko Yoshihara, Satoshi Yoshihara, and Kosei Matsue
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Bortezomib ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Minimal residual disease ,Carfilzomib ,chemistry.chemical_compound ,medicine.anatomical_structure ,Peripheral neuropathy ,chemistry ,Internal medicine ,Medicine ,Bone marrow ,business ,Dexamethasone ,Multiple myeloma ,Lenalidomide ,medicine.drug - Abstract
Background: Owing to the development of novel agents, the rate of complete response (CR) in multiple myeloma (MM) has increased. Additionally, the development of methods for measuring minimal residual disease (MRD) (e.g., multiparameter flow cytometry [MFC] and next-generation sequencing) has enabled us to stratify CR patients according to MRD levels. In this study, we hypothesized that deep response predicts better prognosis in MM. To investigate this hypothesis, we assessed the response of patients treated with carfilzomib + lenalidomide + dexamethasone (KRD) using MFC and compared survival outcomes between different groups defined by the MRD status. Methods: The response of patients with relapsed/refractory MM treated with KRD at four different centers between September 2016 and October 2018 was prospectively investigated using the EuroFlow next-generation flow (EuroFlow-NGF) method. In this method, ammonium chloride-based bulk lysis was used, followed by surface staining with antibodies against CD138-BV421, CD27-BV510, CD38 multiepitope (ME)-FITC, CD56-PE, CD45-PerCP Cy5.5, CD19-PECy7, CD117-APC, and CD81-APC C750 in tube 1 and surface/intracellular staining with antibodies against CD138-BV421, CD27-BV510, CD38 ME-FITC, CD56-PE, CD45-PerCP Cy5.5, CD19-PECy7, CD117-APC, CD81-APC C750, cytoplasmic (cy) Igκ-APC, and cyIgλ-APC C750 after permeabilization in tube 2. MRD levels were assessed using bone marrow (BM) cells after several KRD cycles, with the lower limit of detection set at 1 × 10−5. Presence of high-risk cytogenetics [del 17p, t(4;14) and/or t(14;16)] in BM cells was analyzed through FISH. Results: A total of 21 patients (12 males, 9 females) were treated with KRD and assessed for MRD levels. The median age of these patients was 66 years at KRD initiation (range 30-83 years), and 11 patients had ISS 1, 6 had ISS 2, and 4 had ISS 3. Four patients displayed high-risk chromosomal abnormalities, including del 17p (n = 3) and t(14;16) (n = 1). The median number of prior treatments was 3 (range 1-6); these included bortezomib (n=12), lenalidomide (n=19), and autologous stem-cell transplantation (n=12). The median number of KRD cycles was 4 (range 1-22). The proportion of patients achieving ≥CR and overall response (≥ partial response [PR]) was significantly higher after KRD treatment than the proportion that had been achieved by previous therapies (71% vs. 9.5%, p < 0.001; 100% vs. 71%, p = 0.008, respectively). Pre-KRD responses included 2 stringent CR (sCR), 7 very good PR (VGPR), 6 PR, 3 stable disease, and 3 progressive disease. Post-KRD responses included 13 sCR, 2 CR, 3 VGPR, and 3 PR. A total of 95% (20/21) of patients achieved sCR, and 5% (1/21) VGPR as best response. After KRD, response was upgraded in 19 (90%) patients and maintained in two PR (10%) patients. During and after KRD treatment, MRD negativity was achieved in 12 of 16 (75%) and in 15 of 21 (71%) patients, respectively. The median number of therapy lines after KRD was 1 (range 0-5). All 4 high-risk cytogenetic cases achieved MRD negativity. Among MRD-positive cases, both 2-year progression-free survival (PFS) and 2-year overall survival (OS) from KRD initiation were 100%. Among MRD-negative cases, 2-year PFS and OS from KRD initiation were 92% and 100%, respectively. The median follow-up was 1.8 years (range 0.5-2.5 years). One MRD-negative case showed extramedullary relapse 1.4 years after the last KRD cycle. This patient did not have high-risk cytogenetics and achieved "flow MRD negativity" after two KRD cycles, and the treatment was stopped after 7 KRD cycles due to peripheral neuropathy. Paiva et. al. also reported that only 6 of 225 (3%) MRD-negative patients relapsed. Strikingly, all 6 relapsing cases in the report had extramedullary plasmacytomas at diagnosis; all relapsed with extramedullary plasmacytomas and only 2 developed concomitant serological relapse (ASH 2017, abstract #905). Conclusions: KRD induced deep responses in relapsed/refractory MM patients who eventually displayed excellent PFS. All patients with high-risk cytogenetics achieved EuroFlow-NGF negativity. Post-remission imaging studies such as MRI/PET-CT may be necessary for patients who presented with extramedullary plasmacytomas even when they achieved flow MRD negativity. Figure Disclosures Yoroidaka: Ono Pharmaceutical: Honoraria. Takamatsu:Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Ono pharmaceutical: Honoraria, Research Funding; CSL Behring: Research Funding; SRL: Consultancy, Research Funding; Janssen Pharmaceutical: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Fujimoto Pharmaceutical: Honoraria; Becton, Dickinson and Company: Honoraria; Abbvie: Consultancy; Daiichi-Sankyo Company: Honoraria. Yamashita:Celgene: Honoraria; Ono Pharmaceutical: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Chugai Pharmaceutical Co.,Ltd: Honoraria; Kyowa Kirin: Honoraria; Daiichi-Sankyo Company: Honoraria; TEIJIN PHARMA LIMITED: Honoraria. Murata:Celgene: Honoraria; Ono pharmaceutical: Honoraria. Yoshihara:Kyowa Kirin: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Eisai Co., Ltd.: Honoraria. Yoshihara:Chugai Pharmaceutical Co.,Ltd: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis Pharma K.K.: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Kyowa Kirin: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria. Nakao:Bristol-Myers Squibb: Honoraria; Chugai Pharmaceutical Co.,Ltd: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Celgene: Honoraria; Alaxion Pharmaceuticals: Honoraria; Ohtsuka Pharmaceutical: Honoraria; Novartis Pharma K.K: Honoraria; Kyowa Kirin: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Ono Pharmaceutical: Honoraria; Daiichi-Sankyo Company, Limited: Honoraria; SynBio Pharmaceuticals: Consultancy. Matsue:Takeda Pharmaceutical Company Limited: Honoraria; Novartis Pharma K.K: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene: Honoraria; Ono Pharmaceutical: Honoraria.
- Published
- 2019
25. Adult bovine platelet lysate-derived serum 'NeoSERA' is safe, less ethical and powerful alternative to fetal bovine serum for the culture of mesenchymal stem cells
- Author
-
Masaya Okada, T. Sudo, Yoshihiro Fujimori, Kyoko Yoshihara, Toshihiro Soma, Satoshi Yoshihara, Akiko Hamada, Kenichi Yamahara, and Shunsuke Ohnishi
- Subjects
Cancer Research ,Transplantation ,business.industry ,Bovine spongiform encephalopathy ,Immunology ,Mesenchymal stem cell ,Cell Biology ,medicine.disease ,Regenerative medicine ,Umbilical cord ,Andrology ,Apheresis ,medicine.anatomical_structure ,Oncology ,Cell culture ,Immunology and Allergy ,Medicine ,Platelet lysate ,business ,Genetics (clinical) ,Fetal bovine serum - Abstract
Background & Aim Fetal bovine serum (FBS) is a common component of culture media and usually used for cellular research, as well as recent cell-based medical products. However, due to the high risk of contaminations and the variation from batch to batch, FBS might influence the outcome of research or cellular manufacturing. FBS also contains moral concerns because it harvested from bovine fetuses taken from pregnant cows. In addition, FBS is most expensive part of cell culture. To overcome several problems regarding FBS, we developed a new serum, adult bovine platelet lysate-derived cell culture supplement (NeoSERA), and investigate its usefulness as an alternative to FBS. Methods, Results & Conclusion NeoSERA is produced in Japan, considered to be a negligible bovine spongiform encephalopathy (BSE) risk country. We obtain adult donor bovine blood from animal less than 36 months old according to the regulation of EMA for BSE (EMA/410/01 rev.3). Using apheresis medical devices with closed disposable kits, sterile platelet-rich plasma (PRP) is collected from healthy donor bovine receiving a regular veterinary check. After stimulation and removal of coagulated fibrin by centrifugation, NeoSERA is collected in a completely closed system. To meet the scope of directives that apply to produce medicinal products from the European Agency for the Evaluation of Medicinal Products (EMEA/CVMP/743/00) and the United States Department of Agriculture (9CFR§113.450), NeoSERA is finally g-irradiated at a dose of over 30 kGy. NeoSERA completely meets the standard for biological ingredients in Japan (Ministry of Health, Labour and Welfare Notification No. 375 2014) and also obtained the certificate of eligibility for the raw material of regenerative medicine from Pharmaceuticals and Medical Devices Agency (PMDA, No. 0417002, 2017. 4.17). To test whether NeoSERA is useful for the expansion of mesenchymal stem cells (MSCs), a cell culture experiment was performed. 3 to 5 days after NeoSERA treatment, the proliferation of human bone marrow-, adipose tissue-, umbilical cord- and amnion-derived MSCs was significantly increased (p Our results confirm that safe, less ethical and economical bovine NeoSERA profoundly enhances the proliferation of MSCs for regenerative medicine and several cell lines for vaccine production.
- Published
- 2019
26. Minimal residual disease assessment using EuroFlow in patients with relapsed/refractory multiple myeloma who received carfilzomib+lenalidomide+dexamethasone (KRD) therapy
- Author
-
Kosei Matsue, Ryoichi Murata, Takeshi Yamashita, Hiroyuki Takamatsu, Mikio Ueda, Satoshi Yoshihara, Kyoko Yoshihara, Shinji Nakao, and Takeshi Yoroidaka
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,medicine.disease ,Carfilzomib ,Minimal residual disease ,chemistry.chemical_compound ,chemistry ,EuroFlow ,Internal medicine ,Relapsed refractory ,Medicine ,In patient ,business ,Multiple myeloma ,Dexamethasone ,medicine.drug ,Lenalidomide - Published
- 2019
27. Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial
- Author
-
Hiroki Nishikawa, Satoshi Yoshihara, Hiroyasu Ogawa, Kazuhiro Ikegame, Hiroya Tamaki, Akiko Hamada, Shunsuke Ohnishi, Yoichi M. Ito, Katsuji Kaida, Takanori Teshima, Toshihiro Soma, Norihiro Sato, Kyoko Yoshihara, Yuko Ohsugi, Hiroshi Hayashi, Yoshihiro Fujimori, Masaya Okada, Takayuki Inoue, Hiroaki Iijima, Toshiyuki Isoe, Daigo Hashimoto, Kenichi Yamahara, and Rika Okamoto
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Time Factors ,Adolescent ,Graft vs Host Disease ,Mesenchymal Stem Cell Transplantation ,Cell therapy ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Infusion therapy ,Internal medicine ,Protocol ,medicine ,Clinical endpoint ,Humans ,Amnion ,Aged ,030304 developmental biology ,clinical trials ,0303 health sciences ,business.industry ,Mesenchymal stem cell ,Hematopoietic Stem Cell Transplantation ,Mesenchymal Stem Cells ,General Medicine ,Middle Aged ,Clinical trial ,Transplantation ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,haematology ,Female ,Bone marrow ,Stem cell ,business ,Haematology (Incl Blood Transfusion) - Abstract
IntroductionRegenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for manufacture and marketing as a cell therapy for aGVHD. Our non-clinical studies confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs. This study will aim to evaluate the safety and efficacy of amnion-derived MSCs (AM01) in patients with steroid-refractory aGVHD.Methods and analysisThis study will be a multicentre, single-arm, open-label trial (an interventional study). This clinical trial will begin with a low-dose group, and when safety has been confirmed in at least three cases in the low-dose group, treatment will begin for the high-dose group, for which the safety will also be verified. The primary endpoint is to assess the safety of intravenous infusion therapy of AM01 within 24 hours after intravenous infusion of AM01. The secondary endpoint is to explore the efficacy of intravenous infusion therapy with AM01.Ethics and disseminationThe institutional review boards of all participating hospitals approved this study protocol (latest V3.3.0, 3 August 2018). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate peer-reviewed journal.Trial registration numberUMIN000029945.
- Published
- 2019
28. Low incidence of HHV‐6 reactivation in haploidentical hematopoietic stem cell transplantation with corticosteroid as graft‐vs‐host disease prophylaxis compared with cord blood transplantation
- Author
-
Tatsuya Fujioka, Jun Nakata, Hiroya Tamaki, Masaya Okada, Hiroyasu Ogawa, Takayuki Inoue, Toshihiro Soma, Kazuhiro Ikegame, Ruri Kato, Katsuji Kaida, Kyoko Yoshihara, and Satoshi Yoshihara
- Subjects
Male ,Transplantation Conditioning ,Herpesvirus 6, Human ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,030230 surgery ,Gastroenterology ,0302 clinical medicine ,Adrenal Cortex Hormones ,HLA Antigens ,biology ,Incidence ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,surgical procedures, operative ,Infectious Diseases ,Methylprednisolone ,Histocompatibility ,Corticosteroid ,Female ,030211 gastroenterology & hepatology ,Human herpesvirus 6 ,Cord Blood Stem Cell Transplantation ,Stem cell ,Immunosuppressive Agents ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Roseolovirus Infections ,Human leukocyte antigen ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Aged ,Antilymphocyte Serum ,Retrospective Studies ,Transplantation ,Interleukin-6 ,Umbilical Cord Blood Transplantation ,business.industry ,biology.organism_classification ,DNA, Viral ,Virus Activation ,business - Abstract
Background Human leukocyte antigen (HLA) mismatch and the administration of immunosuppressive agents are considered risks for human herpesvirus 6 (HHV-6) reactivation after stem cell transplantation (SCT). However, the incidence of HHV-6 reactivation in HLA-mismatched related SCT remains unknown. Methods We monitored plasma HHV-6 DNA loads weekly using real-time quantitative polymerase chain reaction for 5 weeks after SCT and compared serum IL-6 levels in HLA-mismatched SCT groups. Results Compared with detection in all 11 umbilical cord blood transplantation (CBT) patients (100%), plasma HHV-6 DNA was detected in only 3 of 42 haplo-SCT patients (7.1%) despite the use of methylprednisolone and antithymocyte globulin as graft-vs-host disease prophylaxis and a reduced-intensity conditioning regimen, respectively. Correspondingly, serum IL-6 levels in haplo-SCT patients were significantly lower than those in CBT patients. No HHV-6-associated encephalitis developed in either groups. Conclusions Neither HLA disparity nor the use of methylprednisolone and antithymocyte globulin were risk factors for HHV-6 reactivation in our haplo-SCT patients. Rather than increasing risk, the administration of immunosuppressive agents potentially prevented HHV-6 reactivation after haplo-SCT by suppressing IL-6 production.
- Published
- 2019
29. Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial.
- Author
-
Kenichi Yamahara, Akiko Hamada, Toshihiro Soma, Rika Okamoto, Masaya Okada, Satoshi Yoshihara, Kyoko Yoshihara, Kazuhiro Ikegame, Hiroya Tamaki, Katsuji Kaida, Takayuki Inoue, Yuko Ohsugi, Hiroki Nishikawa, Hiroshi Hayashi, Ito, Yoichi M., Hiroaki Iijima, Shunsuke Ohnishi, Daigo Hashimoto, Toshiyuki Isoe, and Takanori Teshima
- Abstract
Introduction Regenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for manufacture and marketing as a cell therapy for aGVHD. Our non-clinical studies confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs. This study will aim to evaluate the safety and efficacy of amnionderived MSCs (AM01) in patients with steroid-refractory aGVHD. Methods and analysis This study will be a multicentre, single-arm, open-label trial (an interventional study). This clinical trial will begin with a low-dose group, and when safety has been confirmed in at least three cases in the low-dose group, treatment will begin for the high-dose group, for which the safety will also be verified. The primary endpoint is to assess the safety of intravenous infusion therapy of AM01 within 24 hours after intravenous infusion of AM01. The secondary endpoint is to explore the efficacy of intravenous infusion therapy with AM01. Ethics and dissemination The institutional review boards of all participating hospitals approved this study protocol (latest V3.3.0, 3 August 2018). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate peer-reviewed journal. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
30. Cloning and characterization of two genes encoding dihydroxyacetone kinase from Schizosaccharomyces pombe IFO 0354
- Author
-
Kunio Ohmiya, Shuichi Karita, Tetsuya Kimura, Kunio Imai, Kyoko Yoshihara, Midori Takahashi, Takuya Furuichi, Kazuo Sakka, and Kouichi Suzuki
- Subjects
Genes, Fungal ,Molecular Sequence Data ,Biophysics ,Dihydroxyacetone ,Biochemistry ,Open Reading Frames ,chemistry.chemical_compound ,Structural Biology ,Schizosaccharomyces ,Genetics ,Amino Acid Sequence ,Cloning, Molecular ,Southern blot ,Cloning ,chemistry.chemical_classification ,Bacteria ,Base Sequence ,Sequence Homology, Amino Acid ,biology ,biology.organism_classification ,Molecular biology ,Recombinant Proteins ,Amino acid ,Molecular Weight ,Phosphotransferases (Alcohol Group Acceptor) ,Open reading frame ,chemistry ,Schizosaccharomyces pombe ,Cyclin-dependent kinase 7 ,Sequence Alignment - Abstract
We report the cloning and characterization of two genes encoding dihydroxyacetone kinase (EC 2.7.1.29), SpDAK1 and SpDAK2, from Schizosaccharomyces pombe IFO 0354. The open reading frames of both genes encode 591 amino acids and have Mrs of 62158 and 62170, respectively. Both predicted amino acid sequences exhibited a high identity to each other (99.8%) and relatively high identities (30% to 76%) to other putative dihydroxyacetone kinase gene products. A Western blot analysis showed that these enzymes are induced by glycerol and repressed by glucose. A genomic Southern blot analysis indicated the presence of SpDAK1 and the absence of SpDAK2 in a standard laboratory strain, S. pombe 972h-.
- Published
- 1998
31. A cytogenetic survey of 14,835 consecutive liveborns
- Author
-
Kyoko Yoshihara, Noriko Yabe, Tohru Maeda, Michiko Ohno, and Akira Matsunobu
- Subjects
Chromosome Aberrations ,Male ,Genetics ,Monosomy ,Derivative chromosome ,Marker chromosome ,Infant, Newborn ,Physiology ,Chromosome Disorders ,Chromosomal translocation ,Biology ,Fetal Blood ,medicine.disease ,Japan ,Karyotyping ,medicine ,Chromosome abnormality ,Humans ,Female ,Trisomy ,Sex Chromosome Aberrations ,Genetics (clinical) ,Chromosome 13 ,Chromosomal inversion - Abstract
The results of chromosome studies on cultured umbilical cord blood lymphocytes from a consecutive series of 14,835 liveborn infants (7,608 males and 7,227 females) are described. Ninety-three infants (6.27 per 1,000) had a major chromosome abnormality. Of these, thirty-one infants (2.09 per 1,000) had sex chromosome abnormalities. Seven male infants had a 47,XXY karyotype, five had a 47,XYY karyotype, and three were mosaics. One male had a ring Y chromosome in all cells examined. A pericentric inversion of the Y chromosome was found in one case. Seven female infants had a 47,XXX karyotype, one had a 45,X karyotype and six were mosaics. Sixty-two infants (4.18 per 1,000) had autosomal abnormalities. There were twenty-one infants with trisomy 21 including one mosaic, six infants with trisomy 18, and two infants with trisomy 13 of a Robertsonian translocation type. Three infants had an unbalanced derivative chromosome resulting from a parental reciprocal translocation. Two infants with a partial monosomy of chromosome 13 were detected. There were four infants carrying an additional small marker chromosome. Twenty-four infants (1.62 per 1,000) had a balanced structural rearrangement of the autosomes; eleven with a Robertsonian translocation, eleven with a reciprocal translocation, and two with a pericentric inversion. The incidence of each type of major chromosome abnormality in this study was quite similar to that obtained from previous newborn surveys.
- Published
- 1991
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.