102 results on '"Yumiko Maruyama"'
Search Results
2. P1261: NEGATIVE IMPACT OF HLA-B LEADER MISMATCH ON OUTCOMES OF HCT WITH PTCY FOR LYMPHOID MALIGNANCIES: A RETROSPECTIVE ANALYSIS FROM THE JAPANESE SOCIETY FOR TRANSPLANTATION AND CELLULAR THERAPY
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Minoru Kanaya, Daigo Hashimoto, Hirohisa Nakamae, Takahide Ara, Takahiro Fukuda, Koji Nagafuji, Tetsuya Eto, Nobuhiro Hiramoto, Yumiko Maruyama, Shuichi Ota, Ken-Ichi Matsuoka, Takashi Akasaka, Makoto Onizuka, Tatsuo Ichinohe, Yoshiko Atsuta, and Satoko Morishima
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. Changing trends in the risk factors for second primary malignancies after autologous stem cell transplantation for multiple myeloma before and after the introduction of proteasome inhibitors and immunomodulatory drugs
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Hiroyuki Takamatsu, Tomohiro Matsuda, Shohei Mizuno, Tsutomu Takahashi, Shin-ichi Fuchida, Ichiro Hanamura, Keisuke Kataoka, Nobuhiro Tsukada, Morio Matsumoto, Akira Hangaishi, Noriko Doki, Naoyuki Uchida, Masashi Sawa, Yumiko Maruyama, Shingo Kurahashi, Koji Nagafuji, Yoriko Harazaki, Shinichi Kako, Shinsuke Iida, Tatsuo Ichinohe, Yoshinobu Kanda, Yoshiko Atsuta, Kazutaka Sunami, and Multiple Myeloma Working Group in the Japanese Society for Transplantation and Cellular Therapy
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The incidence of second primary malignancies (SPM) in long-term survivors of multiple myeloma (MM) is increasing because of increased life expectancy. We retrospectively analyzed the risk factors for SPM in patients with MM after autologous stem cell transplantation (ASCT) before and after the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs). In total, 2,340 patients newly diagnosed with MM who underwent ASCT between 1995 and 2016 were enrolled in this study. Forty-three patients developed SPM (29 solid, 12 hematological, and 2 unknown tumors), with cumulative incidence rates of 0.8% and 2.5% at 24 and 60 months, respectively. The cumulative incidence rates of hematological and solid SPM at 60 months were 0.8% and 1.8%, respectively. The overall survival (OS) rate at 60 months after ASCT was 62.9% and the OS rates after the diagnosis of SPM at 24 months were 72.2% for hematological SPM and 70.9% for solid SPM. Multivariate analysis revealed that the use of IMiDs (P=0.024) and radiation (P=0.002) were significant independent risk factors for SPM. The probabilities of developing SPM and death due to other causes (mainly MM) at 60 months were 2.5% and 36.5%, respectively, indicating that the risk of SPM was lower than that of death from MM. Furthermore, SPM between the pre-novel and novel agent eras (ASCT between 2007 and 2016) groups significantly increased (1.9% vs. 4.3% at 60 months; P=0.022). The early occurrence of SPM after ASCT should be monitored cautiously.
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- 2023
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4. Peritransplant glucocorticoids redistribute donor T cells to the bone marrow and prevent relapse after haploidentical SCT
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Takayuki Inoue, Motoko Koyama, Katsuji Kaida, Kazuhiro Ikegame, Kathleen S. Ensbey, Luke Samson, Shuichiro Takahashi, Ping Zhang, Simone A. Minnie, Satoshi Maruyama, Shinichi Ishii, Takashi Daimon, Takahiro Fukuda, Hirohisa Nakamae, Takahide Ara, Yumiko Maruyama, Ken Ishiyama, Tatsuo Ichinohe, Yoshiko Atsuta, Bruce R. Blazar, Scott N. Furlan, Hiroyasu Ogawa, and Geoffrey R. Hill
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Transplantation ,Medicine - Abstract
Patients with acute leukemia who are unable to achieve complete remission prior to allogeneic hematopoietic stem cell transplantation (SCT) have dismal outcomes, with relapse rates well in excess of 60%. Haplo-identical SCT (haplo-SCT) may allow enhanced graft-versus-leukemia (GVL) effects by virtue of HLA class I/II donor-host disparities, but it typically requires intensive immunosuppression with posttransplant cyclophosphamide (PT-Cy) to prevent lethal graft-versus-host disease (GVHD). Here, we demonstrate in preclinical models that glucocorticoid administration from days –1 to +5 inhibits alloantigen presentation by professional recipient antigen presenting cells in the gastrointestinal tract and prevents donor T cell priming and subsequent expansion therein. In contrast, direct glucocorticoid signaling of donor T cells promotes chemokine and integrin signatures permissive of preferential circulation and migration into the BM, promoting donor T cell residency. This results in significant reductions in GVHD while promoting potent GVL effects; relapse in recipients receiving glucocorticoids, vehicle, or PT-Cy was 12%, 56%, and 100%, respectively. Intriguingly, patients with acute myeloid leukemia not in remission who received unmanipulated haplo-SCT and peritransplant glucocorticoids also had an unexpectedly low relapse rate at 1 year (32%; 95% CI, 18%–47%) with high overall survival at 3 years (58%; 95% CI, 38%–74%). These data highlight a potentially simple and effective approach to prevent relapse in patients with otherwise incurable leukemia that could be studied in prospective randomized trials.
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- 2021
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5. Cerebral radiation necrosis and brain abscess as delayed complications after carbon ion radiotherapy against nasal carcinoma
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Masanori Kurimoto, Yumiko Maruyama, Yayoi Tsukada, Hiromichi Yamamoto, and Kiyoshi Takagawa
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Nasal carcinoma ,Adenoid cystic carcinoma ,Carbon ion radiotherapy ,Radiation necrosis ,Brain abscess ,Surgery ,RD1-811 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
A case of radiation induced delayed brain necrosis associated with bacterial brain abscess is reported. A 50-year-old Japanese man with adenoid cystic carcinoma underwent carbon ion radiotherapy and the cancer disappeared on MRI one year later. The MRI taken 30 months after the therapy showed white matter edema of the left temporal lobe suggesting a radiation injury. He suffered atypical trigeminal neuralgia at the V1 territory. He became delirious as Glasgow coma scale: 9 by increased intracranial pressure. He suffered aspiration pneumonia and sepsis. 6.5 years later, an emergent craniotomy was chosen for his increased intracranial pressure and aggravating neurological symptoms. Left temporal pole and necrotic tissues were removed and bacterial brain abscess was found. Brain abscess was managed with antibiotic drugs. His clinical symptoms improved. Concerning with brain abscess in this case, radiotherapy might break down of the blood-brain barrier and hematogenous bacterial brain abscess was formed by chance he suffered from sepsis before craniotomy. Carbon ion radiotherapy is promising treatment for nasal carcinomas, but radiation induced late complications should be cared.
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- 2021
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6. Fatal Epstein-Barr Virus Reactivation in an Acquired Aplastic Anemia Patient Treated with Rabbit Antithymocyte Globulin and Cyclosporine A
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Tohru Takahashi, Yumiko Maruyama, Mayuko Saitoh, Hideto Itoh, Mitsuru Yoshimoto, and Masayuki Tsujisaki
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Epstein-Barr virus (EBV) associated lymphoproliferative disorder (LPD) after immunosuppressive therapy for aplastic anemia (AA) is extremely rare in a nontransplant setting and has not been well described. This report describes a severe AA patient in whom fatal EBV-LPD developed after being treated with rabbit antithymocyte globulins (ATG) and cyclosporine A (CsA). An 81-year-old man was diagnosed as having severe AA. He was started on CsA followed by administration of ATG for five consecutive days. One month after the start of ATG, persistent fever which was not responsive to antibiotics or antifungal agents developed and atypical lymphocytes emerged in peripheral blood. Repeated blood cultures were negative. An extremely high level of EBV virus in his peripheral blood plasma was detected by means of a quantitative real-time PCR assay. Even after the cessation of CsA, the fever persisted and the peripheral atypical lymphocytes proliferated rapidly. The patient suffered from respiratory failure, liver dysfunction, and metabolic acidosis. Rituximab was administered without success and he died.
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- 2015
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7. Cardiac Tamponade as a Recurrence of Angioimmunoblastic T-Cell Lymphoma with the Detection of a p.Gly17Val RHOA Mutation in the Pericardial Effusion
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Yuri, Tsuboi, Yumoe, Iimura, Fumiaki, Matsumura, Toru, Nanmoku, Sakurako, Suma, Ryota, Matsuoka, Tomoki, Nakagawa, Daishi, Nakagawa, Yasuhito, Suehara, Keiichiro, Hattori, Kimi, Sato, Yumiko, Maruyama, Tatsuhiro, Sakamoto, Yasuhisa, Yokoyama, Takayasu, Kato, Naoki, Kurita, Hidekazu, Nishikii, Naoshi, Obara, Masaki, Ieda, Shigeru, Chiba, and Mamiko, Sakata-Yanagimoto
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Internal Medicine ,General Medicine - Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is an intractable type of T-cell lymphoma. We and others have identified that the p.Gly17Val RHOA mutation is specifically identified in AITL. We herein report a patient whose condition deteriorated, resulting from massive pericardial effusion one month after undergoing autologous transplantation for AITL. He was diagnosed with cardiac tamponade caused by AITL recurrence in the presence of the p.Gly17Val RHOA mutation as well as T-lineage cells with an aberrant immune-phenotype in the pericardial effusion. This case suggests that a precision medicine approach by detecting the presence of a p.Gly17Val RHOA mutation is useful for the management of AITL.
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- 2023
8. Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI
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Mari Morita‐Fujita, Yasuyuki Arai, Tadakazu Kondo, Kaito Harada, Naoyuki Uchida, Takashi Toya, Yukiyasu Ozawa, Takahiro Fukuda, Shuichi Ota, Makoto Onizuka, Yoshinobu Kanda, Yumiko Maruyama, Satoru Takada, Toshiro Kawakita, Takahide Ara, Tatsuo Ichinohe, Takafumi Kimura, Yoshiko Atsuta, and Shinichi Kako
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Adult ,Cancer Research ,Oncology ,VP16/CY/TBI ,Humans ,Hematology ,General Medicine ,Registries ,acute lymphoblastic leukemia ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Philadelphia chromosome ,Whole-Body Irradiation ,Retrospective Studies - Abstract
The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph-) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph- ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37-0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph- ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph- ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL.
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- 2022
9. Severe short-term adverse events in related bone marrow or peripheral blood stem cell donors
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Ryu Yanagisawa, Tsuneaki Hirakawa, Noriko Doki, Kazuhiro Ikegame, Ken-ichi Matsuoka, Takahiro Fukuda, Hirohisa Nakamae, Shuichi Ota, Nobuhiro Hiramoto, Jun Ishikawa, Takahide Ara, Masatsugu Tanaka, Yuhki Koga, Toshiro Kawakita, Yumiko Maruyama, Yoshinobu Kanda, Masayuki Hino, Yoshiko Atsuta, Hiromasa Yabe, and Nobuhiro Tsukada
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Hematology - Abstract
The incidence of severe adverse events (SAEs) and associated risk factors in hematopoietic cell transplantation donors needs to be clarified for related donors (relatives of the transplant recipient), whose criteria for donation are more lenient than for unrelated donors. Data from related donors registered in the Japanese national data registry database between 2005 and 2021 were evaluated to determine the association of short-term SAE incidence with donor characteristics at registration.Fourteen of 4339 bone marrow (BM) donors (0.32%) and 54 of 10,684 peripheral blood stem cell (PBSC) donors (0.51%) experienced confirmed SAEs during the short donation period. No deaths were observed. Past medical history was a common risk factor for SAEs in both BM and PBSC donors. Age of 60 years or older and female sex were identified as risk factors for SAEs in PBSC donors. Female sex was also a risk factor for poor mobilization, which resulted in discontinuation of PBSC collection.Although donors should be selected carefully, a certain level of safety is ensured for related donors in Japan. Donor safety should be further increased by improving the selection method for related donors and extending the follow-up period.
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- 2022
10. Intensified conditioning regimens improved disease‐free survival and engraftment after unrelated single‐unit cord blood transplantation but not after matched sibling or matched unrelated donor allogeneic hematopoietic cell transplantation
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Takaaki, Konuma, Junya, Kanda, Naoyuki, Uchida, Akihiko, Nishijima, Masatsugu, Tanaka, Yukiyasu, Ozawa, Masashi, Sawa, Makoto, Onizuka, Shuichi, Ota, Yumiko, Maruyama, Yoshinobu, Kanda, Toshiro, Kawakita, Takahide, Ara, Tetsuya, Eto, Hirohisa, Nakamae, Takafumi, Kimura, Takahiro, Fukuda, and Yoshiko, Atsuta
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Cancer Research ,Oncology ,Hematology ,General Medicine - Abstract
The impact of conditioning intensity on different donor groups has been unclear in allogeneic transplantation. The objective of this study was to clarify the effect of conditioning intensity on disease-free survival (DFS), relapse, non-relapse mortality (NRM), neutrophil engraftment, and graft-versus-host disease for each donor type. We retrospectively evaluated the effect of conditioning intensity on transplant outcomes for patients with acute leukemia or myelodysplastic syndrome aged between 16 and 60 years in Japan using the transplant conditioning intensity (TCI) scoring system. A total of 8526 patients who received first allogeneic transplantation from 6/6 antigen-matched sibling donor (MSD, n = 2768), 8/8 allele-matched unrelated donor (MUD, n = 2357), and unrelated single-cord blood (UCB, n = 3401) were eligible for the analyses. Compared to conditioning with TCI score 4.0, which was corresponds to conventional myeloablative conditioning, including cyclophosphamide with total body irradiation 12 Gy or busulfan 12.8 mg, and was considered as the reference group in the multivariate analyses, intensified conditioning with TCI score ≥4.5 improved DFS (hazard ratio [HR],0.81, P 0.001) and relapse rate (HR, 0.70, P 0.001) but only after UCB transplants and not MSD and MUD transplants. In contrast, NRM was higher after intensified conditioning with TCI score ≥4.5 for MSD (HR, 1.39, P = 0.008) and MUD (HR, 1.47, P = 0.002) transplants but not UCB transplants (HR, 1.12, P = 0.240). Neutrophil engraftment was also significantly higher after intensified conditioning with TCI score ≥4.5 but only for UCB transplants (HR, 1.24, P 0.001), whereas it was significantly lower after reduced-intensity conditioning with TCI score ≤3.5 for MSD transplants only (HR, 0.82, P 0.001). These data demonstrated that an intensified conditioning regimen improved survival and engraftment rate only after a UCB transplants. Therefore, TCI scoring system could enable the optimization of conditioning intensity according to donor type, particularly in terms of survival and engraftment.
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- 2022
11. Comparable survival outcomes with haploidentical stem cell transplantation and unrelated bone marrow transplantation
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Yoshiko Atsuta, Junichi Sugita, Hirohisa Nakamae, Yumiko Maruyama, Ken Ishiyama, Souichi Shiratori, Takahiro Fukuda, Mio Kurata, Naoki Shingai, Yukiyasu Ozawa, Masayoshi Masuko, Koji Nagafuji, Satoru Takada, Shinichi Kako, Yoshinobu Kanda, Junya Kanda, Tatsuo Ichinohe, and Takanori Teshima
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Leukemia, Myeloid, Acute ,Transplantation ,Recurrence ,Hematopoietic Stem Cell Transplantation ,Humans ,Graft vs Host Disease ,Hematology ,Unrelated Donors ,Cyclophosphamide ,Bone Marrow Transplantation ,Retrospective Studies - Abstract
We retrospectively compared outcomes of unrelated donor bone marrow transplant (UBMT) and HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCy-haploPBSCT) using the Japanese registry data. Recipients of first HCT for acute leukemia and myelodysplastic syndromes between 2012 and 2015 were included. The analyzed subjects comprised UBMT recipients with 8/8 matched HLA alleles (n = 1470), 7/8 matched alleles (n = 859), 6/8 matched alleles (n = 186), and recipients of PTCy-haploPBSCT (n = 133). In multivariate analyses with 8/8 matched UBMT as the reference, PTCy-haploPBSCT showed similar overall mortality, decreased risk of non-relapse mortality (NRM), increased risk of relapse, and decreased risk of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD. Adjusted probabilities for 8/8 matched UBMT, PTCy-haploPBSCT, and 7/8 and 6/8 matched UBMT groups at 2 years post-transplant were 61%, 60%, 58%, and 52% for overall survival, 23%, 28%, 21%, and 19% for relapse, and 20%, 7%, 24%, and 33% for NRM. PTCy-haploPBSCT was associated with remarkably low NRM, contributing to survival outcomes that were comparable to 8/8 matched UBMT. The higher relapse rate in the PTCy-haploPBSCT group might be associated with the higher proportion of high-risk patients. PTCy-haploPBSCT may be a viable alternative when HLA-matched related donors are not available.
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- 2022
12. Overcoming minimal residual disease using intensified conditioning with medium-dose etoposide, cyclophosphamide and total body irradiation in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults
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Kaito Harada, Mari Morita-Fujita, Takahiro Fukuda, Yukiyasu Ozawa, Noriko Doki, Masako Toyosaki, Yumiko Maruyama, Yoshinobu Kanda, Takashi Ashida, Tetsuya Eto, Satoru Takada, Naoyuki Uchida, Tatsuo Ichinohe, Junya Kanda, Makoto Onizuka, Yoshiko Atsuta, Shinichi Kako, and Yasuyuki Arai
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Adult ,Cancer Research ,Transplantation ,Neoplasm, Residual ,Transplantation Conditioning ,myeloablative conditioning ,Immunology ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,acute lymphoblastic leukemia ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Philadelphia chromosome ,etoposide ,Oncology ,Acute Disease ,Immunology and Allergy ,Humans ,Cyclophosphamide ,Genetics (clinical) ,Whole-Body Irradiation ,Retrospective Studies - Abstract
BACKGROUND AIMS: An intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic impacts of the addition of VP16 to cyclophosphamide (CY) and total body irradiation (TBI) in patients with Philadelphia chromosome-positive (Ph+) ALL with regard to minimal residual disease (MRD) status have not been elucidated. METHODS: The authors retrospectively compared the outcomes of patients with Ph+ ALL who underwent allogeneic transplantation following VP16/CY/TBI (n=101) and CY/TBI (n=563). RESULTS: At 4 years, the VP16/CY/TBI group exhibited significantly better disease-free survival (DFS) (72.6% versus 61.7%, P=0.027) and relapse rate (11.5% versus 21.1%, P=0.020) and similar non-relapse mortality (16.0% versus 17.2%, P=0.70). In subgroup analyses, the beneficial effects of the addition of VP16 on DFS were more evident in patients with positive MRD status (71.2% versus 48.4% at 4 years, P=0.022) than those with negative MRD status (72.8% versus 66.7% at 4 years, P=0.24). Although MRD positivity was significantly associated with worse DFS in patients who received CY/TBI (48.4% versus 66.7%, P < 0.001), this was not the case in those who received VP16/CY/TBI (71.2% versus 72.8%, P=0.86). CONCLUSIONS: This study demonstrated the benefits of the addition of VP16 in Ph+ ALL patients, especially those with positive MRD status. VP16/CY/TBI could be a potential strategy to overcome the survival risk of MRD positivity.
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- 2022
13. A Case of Acute Suppurative Thyroiditis Causing Deep Neck Infection with Esophageal Perforation
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Yayoi Tsukada, Yumiko Maruyama, Daisuke Uno, Yuki Kitagawa, and Tomokazu Yoshizaki
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- 2022
14. Repeated immunosuppressive rabbit antithymocyte globulin therapy for adult patients with relapsed or refractory aplastic anemia.
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Tatsuhiro Sakamoto, Naoshi Obara, Yumiko Maruyama, Takayasu Kato, Naoki Kurita, Keiichiro Hattori, Yasuhito Suehara, Hidekazu Nishikii, Yasuhisa Yokoyama, Mamiko Sakata-Yanagimoto, Kensuke Usuki, and Shigeru Chiba
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APLASTIC anemia ,CYCLOSPORINE ,GLOBULINS ,ANEMIA treatment ,SALVAGE therapy - Abstract
Objectives: Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporin A is the standard treatment for aplastic anemia (AA). However, the efficacy of repeated IST with rabbit ATG (rATG) as salvage therapy remains unclear in patients with relapsed or refractory AA. Methods: We retrospectively evaluated the efficacy and safety of IST2 with rATG (IST2-rATG) in 19 consecutive patients with relapsed or refractory AA who received first-line IST with rATG in two centers between 2009 and 2020. Results: The overall 6-month response rate of the patients was 58%. The response rates were similar between patients with relapsed and refractory AA. The presence of glycophosphatidylinositol-deficient blood cells was associated with a better response to IST2-rATG. Despite retreatment with the same rATG, serum disease and severe allergic reactions were not observed. Conclusion: IST2-rATG is effective and safe for the treatment of adult patients with relapsed and refractory AA after receiving first-line IST with rATG. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Neutralizing antibody levels and epidemiological information of patients with breakthrough COVID-19 infection in Toyama, Japan
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Hideki Tani, Noriko Inasaki, Takahisa Shimada, Yumiko Saga, Hiroyasu Kaya, Yumiko Maruyama, Sadaya Matano, Hiroyuki Itoh, Tatsuhiko Kashii, Emiko Yamazaki, Shunsuke Yazawa, Masae Itamochi, and Kazunori Oishi
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Microbiology (medical) ,Infectious Diseases ,General Medicine - Abstract
Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has exploded owing to the emergence of various SARS-CoV-2 variants and has become a major problem at present. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Analysis of 44 specimens diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta variants of pseudotyped viruses in 40 specimens. In contrast, almost no neutralizing activity was observed against the Omicron BA.1 variant. Many cases without neutralizing activity or BI were immunosuppressed individuals. The results of this study show that BI occurs even when there are sufficient neutralizing antibodies in the blood due to exposure to close contacts at the time of infection. Thus, even after vaccination, sufficient precautions must be taken to prevent infection.
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- 2023
16. Pott's Puffy Tumor in an Adult
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Daisuke Uno, Yumiko Maruyama, Yayoi Tsukada, Yuki Kitagawa, and Tomokazu Yoshizaki
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- 2022
17. Supplementary Data from Genomic Screening for Genes Silenced by DNA Methylation Revealed an Association between RASD1 Inactivation and Dexamethasone Resistance in Multiple Myeloma
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Yasuhisa Shinomura, Minoru Toyota, Tadao Ishida, Takashi Tokino, Kohzoh Imai, Mitsuru Mori, Toshiaki Hayashi, Hajime Sakai, Hideki Asaoku, Yasushi Sasaki, Isao Tarasawa, Yumiko Maruyama, Hiromu Suzuki, Hiroshi Yasui, Reo Maruyama, and Masanori Nojima
- Abstract
Supplementary Data from Genomic Screening for Genes Silenced by DNA Methylation Revealed an Association between RASD1 Inactivation and Dexamethasone Resistance in Multiple Myeloma
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- 2023
18. Data from Genomic Screening for Genes Silenced by DNA Methylation Revealed an Association between RASD1 Inactivation and Dexamethasone Resistance in Multiple Myeloma
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Yasuhisa Shinomura, Minoru Toyota, Tadao Ishida, Takashi Tokino, Kohzoh Imai, Mitsuru Mori, Toshiaki Hayashi, Hajime Sakai, Hideki Asaoku, Yasushi Sasaki, Isao Tarasawa, Yumiko Maruyama, Hiromu Suzuki, Hiroshi Yasui, Reo Maruyama, and Masanori Nojima
- Abstract
Purpose: Epigenetic changes such as DNA methylation play a key role in the development and progression of multiple myeloma. Our aim in the present study was to use genomic screening to identify genes targeted for epigenetic inactivation in multiple myeloma and assess their role in the development of resistance to dexamethasone.Experimental Design: Gene expression was examined using microarray screening, reverse transcription-PCR, and real-time quantitative PCR. DNA methylation was examined using bisulfite PCR, bisulfite sequencing, and bisulfite pyrosequencing in 14 multiple myeloma cell lines, 87 multiple myeloma specimens, and 12 control bone marrow samples. WST-8 assays were used to assess cell viability after treatment with 5-aza-2′-deoxycytidine and/or dexamethasone.Results: Microarray analysis was done to screen for genes up-regulated by 5-aza-2′-deoxycytidine. In RPMI8226 cells, 128 genes were up-regulated, whereas 83 genes were up-regulated in KMS12PE cells. Methylation of 22 genes with CpG islands in their 5′ regions, including RASD1, was confirmed. Methylation of RASD1 was associated with its inactivation, which correlated with resistance to dexamethasone. Treating multiple myeloma cells with 5-aza-2′-deoxycytidine restored sensitivity to dexamethasone. Methylation of RASD1 was also detected in a subset of primary multiple myeloma specimens, and the levels of methylation were increased after repeated antitumor treatments. Gene signature analysis revealed various genes to be synergistically induced by treatment with a combination of 5-aza-2′-deoxycytidine plus dexamethasone.Conclusion: Our findings indicate that epigenetic inactivation of genes, including RASD1, plays a key role in the development of dexamethasone resistance in multiple myeloma. Moreover, they show the utility of demethylation therapy in cases of advanced multiple myeloma.
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- 2023
19. Supplementary Materials & Methods, Figures S1-S4, and Tables S1-S6 from Comparative Genome Analysis Identifies the Vitamin D Receptor Gene as a Direct Target of p53-Mediated Transcriptional Activation
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Takashi Tokino, Yasuhisa Shinomura, Kohzoh Imai, Haruyuki Tatsumi, Yumiko Maruyama, Mutsumi Ohe-Toyota, Kimishige Akino, Hiromu Suzuki, Hiroaki Mita, Hirofumi Akashi, Yasushi Sasaki, Minoru Toyota, Fumio Aoki, and Reo Maruyama
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Methods paragraph, 4 Figures, 6 Tables
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- 2023
20. Data from Comparative Genome Analysis Identifies the Vitamin D Receptor Gene as a Direct Target of p53-Mediated Transcriptional Activation
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Takashi Tokino, Yasuhisa Shinomura, Kohzoh Imai, Haruyuki Tatsumi, Yumiko Maruyama, Mutsumi Ohe-Toyota, Kimishige Akino, Hiromu Suzuki, Hiroaki Mita, Hirofumi Akashi, Yasushi Sasaki, Minoru Toyota, Fumio Aoki, and Reo Maruyama
- Abstract
p53 is the most frequently mutated tumor suppressor gene in human neoplasia and encodes a transcriptional coactivator. Identification of p53 target genes is therefore key to understanding the role of p53 in tumorigenesis. To identify novel p53 target genes, we first used a comparative genomics approach to identify p53 binding sequences conserved in the human and mouse genome. We hypothesized that potential p53 binding sequences that are conserved are more likely to be functional. Using stringent filtering procedures, 32 genes were newly identified as putative p53 targets, and their responsiveness to p53 in human cancer cells was confirmed by reverse transcription-PCR and real-time PCR. Among them, we focused on the vitamin D receptor (VDR) gene because vitamin D3 has recently been used for chemoprevention of human tumors. VDR is induced by p53 as well as several other p53 family members, and analysis of chromatin immunoprecipitation showed that p53 protein binds to conserved intronic sequences of the VDR gene in vivo. Introduction of VDR into cells resulted in induction of several genes known to be p53 targets and suppression of colorectal cancer cell growth. In addition, p53 induced VDR target genes in a vitamin D3-dependent manner. Our in silico approach is a powerful method for identification of functional p53 binding sites and p53 target genes that are conserved among humans and other organisms and for further understanding the function of p53 in tumorigenesis. (Cancer Res 2006; 66(9): 4574-83)
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- 2023
21. A Case of Nasopharyngeal Lipoma
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Yayoi Tsukada, Yumiko Maruyama, Yuki Kitagawa, and Tomokazu Yoshizaki
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Otorhinolaryngology - Published
- 2022
22. A Case of Skull Base Osteomyelitis Caused by Fungi
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Yayoi Tsukada and Yumiko Maruyama
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Otorhinolaryngology - Published
- 2022
23. [Acute myeloid leukemia harboring NUP98::DDX10]
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Naoki, Kurita, Takayasu, Kato, Toru, Nanmoku, Yumiko, Maruyama, Yasuhito, Suehara, Keiichiro, Hattori, Tatsuhiro, Sakamoto, Yasuhisa, Yokoyama, Chikashi, Yoshida, Yuri, Tsuboi, Naoshi, Obara, Hidekazu, Nishikii, Mamiko, Sakata-Yanagimoto, and Shigeru, Chiba
- Subjects
Nuclear Pore Complex Proteins ,DEAD-box RNA Helicases ,Leukemia, Myeloid, Acute ,Neoplasm, Residual ,Recurrence ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Humans ,Female ,Middle Aged ,Prognosis - Abstract
NUP98::DDX10 is a rare fusion gene associated with acute myeloid leukemia (AML), for which the prognosis and indication for allogeneic hematopoietic stem cell transplantation are unknown. A 48-year-old woman was diagnosed with AML harboring NUP98::DDX10. The results of quantitative RT-PCR of the fusion mRNA as a minimal residual disease (MRD) marker guided the treatment. In August 2019, the patient achieved hematological remission following standard remission induction therapy with idarubicin and cytarabine. After four cycles of consolidation therapies, MRD was detected, and she underwent allogeneic stem cell transplantation in May 2020. As MRD persisted in June, the immunosuppressant was stopped and three cycles of azacitidine were administered. Despite this, a hematological relapse occurred in January 2021 that was resistant to high-dose cytarabine and an investigational agent. She died as a result of the disease's progression. Thus, a second thought should be given to the timing of transplantation, the bridging, and the intervention for relapse after transplantation. The cases must be accumulated.
- Published
- 2022
24. Usefulness of Abscess Tonsillectomy for the Treatment of Severe Peritonsillar Abscess
- Author
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Yumiko Maruyama, Tomomi Yoshikawa, Yayoi Tsukada, Yuki Kitagawa, Tomokazu Yoshizaki, and Shoko Kojima
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,medicine ,Peritonsillar Abscess ,business ,Abscess ,medicine.disease ,Tonsillectomy ,Surgery - Published
- 2021
25. Fludarabine/busulfan versus busulfan/cyclophosphamide as myeloablative conditioning for myelodysplastic syndrome: a propensity score-matched analysis
- Author
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Hidehiro Itonaga, Yuho Najima, Shuhei Kurosawa, Toshiro Kawakita, Shuichi Ota, Yoshimitsu Shimomura, Ken-ichi Matsuoka, Yumiko Maruyama, Yukiyasu Ozawa, Junya Kanda, Yoshiko Atsuta, Takeshi Kobayashi, Kazunori Imada, Jun Aoki, Takahiro Fukuda, Shinichi Kako, Yoshinobu Kanda, and Hideyuki Nakazawa
- Subjects
Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Cumulative incidence ,Propensity Score ,Busulfan ,Retrospective Studies ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Confidence interval ,Fludarabine ,Leukemia, Myeloid, Acute ,Myelodysplastic Syndromes ,Propensity score matching ,business ,Vidarabine ,medicine.drug - Abstract
Myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) is effective for acute myeloid leukemia. However, the effectiveness of Flu/Bu4 for myelodysplastic syndrome (MDS) remains poorly understood. Therefore, we retrospectively analyzed nationwide registry data in Japan from 2006 to 2018 and compared transplant outcomes of adult MDS patients receiving Flu/Bu4 and busulfan/cyclophosphamide (Bu4/Cy) using propensity score (PS) matching. The primary endpoint was overall survival (OS). Among 2,482 MDS patients, 153 patients were assigned each to the Flu/Bu4 and Bu4/Cy groups. The 3-year OS rates were 52.7% (95% confidence interval [CI], 43.8-60.8%) and 49.5% (95% CI, 40.8-57.6%) in the Flu/Bu4 and Bu4/Cy group, respectively (P = 0.548). The 3-year progression-free survival (P = 0.858), the cumulative incidence of relapse (P = 0.536), and cumulative incidence of non-relapse mortality (P = 0.684) were not significantly different between the two groups. According to the findings of subgroup analyses, no patient had a favorable OS when using either of the two regimens. In conclusion, although our PS-matched cohort mainly comprised older patients who had a low hematopoietic cell transplantation-comorbidity index and low-risk disease status, Flu/Bu4 could be an alternative to Bu4/Cy for MDS patients prior to allo-HSCT.
- Published
- 2021
26. Difference in outcomes following allogeneic hematopoietic cell transplantation for patients with acute myeloid leukemia and myelodysplastic syndromes
- Author
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Hirohisa Nakamae, Satoshi Yamasaki, Masatsugu Tanaka, Yoshinobu Kanda, Tatsuo Ichinohe, Takaaki Konuma, Toshiro Kawakita, Naoki Shingai, Yukiyasu Ozawa, Makoto Onizuka, Yumiko Maruyama, Tetsuya Eto, Kaito Harada, Masamitsu Yanada, Shingo Yano, Souichi Shiratori, Shohei Mizuno, Ken-ichi Matsuoka, Yoshiko Atsuta, Jun Aoki, Hiroya Tamaki, Masashi Sawa, and Naoyuki Uchida
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Disease ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Overall survival ,Humans ,Medicine ,Relapse risk ,neoplasms ,Retrospective Studies ,Hematopoietic cell ,business.industry ,Myelodysplastic syndromes ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,medicine.disease ,Transplantation ,Leukemia, Myeloid, Acute ,Myelodysplastic Syndromes ,business - Abstract
To evaluate whether outcomes following allogeneic hematopoietic cell transplantation differ according to disease type, a three-way comparison for patients with de novo acute myeloid leukemia (AML) (n = 3318), AML evolving from myelodysplastic syndromes (MDS) (n = 208), and MDS with excess blasts (MDS-EB) (n = 994) was performed. The 5-year probabilities of overall survival (OS) for de novo AML, AML evolving from MDS, and MDS-EB were 60%, 42%, and 41% (p < 0.001), respectively. Multivariate analysis revealed that, compared to de novo AML, AML evolving from MDS was associated with a higher risk of NRM (p = 0.030) and MDS-EB with a higher risk of relapse (p < 0.001), both leading to lower OS (p = 0.010 and p < 0.001, respectively). These findings demonstrate inter-disease differences in post-transplant outcomes and highlight the needs to reduce NRM for AML evolving from MDS and to reduce relapse for MDS-EB.
- Published
- 2021
27. Effect of the COVID-19 pandemic on allogeneic stem cell transplantation in Japan
- Author
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Yoshimitsu Shimomura, Tetsuhisa Kitamura, Masashi Nishikubo, Tomotaka Sobue, Naoyuki Uchida, Noriko Doki, Masatsugu Tanaka, Ayumu Ito, Jun Ishikawa, Takahide Ara, Shuichi Ota, Makoto Onizuka, Masashi Sawa, Yukiyasu Ozawa, Yumiko Maruyama, Kazuhiro Ikegame, Yoshinobu Kanda, Tatsuo Ichinohe, Takahiro Fukuda, Shinichiro Okamoto, Takanori Teshima, and Yoshiko Atsuta
- Subjects
Hematology - Abstract
The coronavirus disease 2019 (COVID-19) pandemic affected healthcare quality and access worldwide and may also have negatively affected the frequency and outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated the effect of the pandemic on allogeneic HSCT in Japan. Our subjects were patients who received allogeneic HSCT during January 2018-December 2020 in Japan. We assessed differences in yearly number of allogeneic HSCTs and 1-year outcomes in 2020 versus both 2019 and 2018. The total number of patients who received allogeneic HSCT increased from 3621 patients in 2018 and 3708 patients in 2019 to 3865 patients in 2020. Some following changes in allogeneic HSCT methods were observed: patients were older, fewer patients received bone marrow transplantation, fewer patients received transplants from unrelated donors, fewer patients received transplants from matched donors, more patients received reduced-intensity conditioning, and fewer patients received anti-thymocyte globulin in 2020 compared with previous years. HSCT outcomes were not affected, as 1-year overall survival was not significantly different (65.8% in 2020, vs. 66.5% in 2019 and 66.4% in 2018). Our results suggest that we can maintain transplant care during the pandemic by controlling the spread of COVID-19 and modifying HSCT methods.
- Published
- 2022
28. Haploidentical transplantation with post-transplant cyclophosphamide versus single cord blood transplantation for myelodysplastic syndrome: A retrospective study from the Adult Myelodysplastic Syndrome Working Group of the Japanese Society for Transplantation and Cellular Therapy (JSTCT)
- Author
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Takaaki Konuma, Yoshimitsu Shimomura, Ken Ishiyama, Takahide Ara, Hirohisa Nakamae, Nobuhiro Hiramoto, Tetsuya Eto, Yumiko Maruyama, Koji Nagafuji, Jun Ishikawa, Naoyuki Uchida, Masatsugu Tanaka, Makoto Onizuka, Yasunori Ueda, Naoyuki Anzai, Takafumi Kimura, Yoshinobu Kanda, Takahiro Fukuda, and Yoshiko Atsuta
- Subjects
Adult ,Transplantation Conditioning ,Japan ,Myelodysplastic Syndromes ,Transplantation, Haploidentical ,Hematopoietic Stem Cell Transplantation ,Humans ,Graft vs Host Disease ,Hematology ,Cord Blood Stem Cell Transplantation ,Cyclophosphamide ,Retrospective Studies - Published
- 2022
29. Advantages of Higher Busulfan Dose Intensity in Fludarabine-Combined Conditioning for Patients with Acute Myeloid Leukemia Undergoing Cord Blood Transplantation
- Author
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Sho Shibata, Yasuyuki Arai, Tadakazu Kondo, Shohei Mizuno, Kaito Harada, Shigesaburo Miyakoshi, Naoyuki Uchida, Yumiko Maruyama, Tetsuya Eto, Yuna Katsuoka, Kosei Matsue, Kaichi Nishiwaki, Satoru Takada, Noriko Doki, Mitsuru Itoh, Koji Nagafuji, Toshiro Kawakita, Junji Tanaka, Takahiro Fukuda, Yoshiko Atsuta, and Masamitsu Yanada
- Subjects
Fludarabine ,Transplantation ,Acute myeloid leukemia ,Cord blood transplantation ,Conditioning regimen ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology ,Busulfan - Abstract
The alkylating agent busulfan is commonly used as conditioning in allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML). However, a consensus has not yet been reached regarding the optimal busulfan dose in cord blood transplantation (CBT). Therefore, we conducted this large nationwide cohort study to retrospectively analyze the outcomes of CBT in patients with AML receiving busulfan at intermediate (6.4 mg/kg i.v.; BU2) or higher (12.8 mg/kg i.v.; BU4) doses within a fludarabine/i.v. busulfan (FLU/BU) regimen. Among 475 patients who underwent their first CBT following FLU/BU conditioning between 2007 and 2018, 162 received BU2 and 313 received BU4. Multivariate analysis identified BU4 as a significant factor for longer disease-free survival (hazard ratio [HR], .85; 95% confidence interval [CI], .75 to .97; P = .014) and a lower relapse rate (HR, .84; 95% CI, .72 to .98; P = .030). No significant differences were observed in non-relapse mortality between BU4 and BU2 (HR, 1.05; 95% CI, .88-1.26; P = .57). Subgroup analyses showed that BU4 provided significant benefits for patients who underwent transplantation while not in complete remission (CR) and those age
- Published
- 2023
30. Indirectly Recognizable Epitopes Derived from Recipient Mismatched HLA-B Are Associated with Adverse Prognosis in Single-Unit Cord Blood Transplantation
- Author
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Takeshi Sugio, Koji Kato, Naoyuki Uchida, Kohta Miyawaki, Matthias Niemann, Eric Spierings, Makoto Onizuka, Yasufumi Uehara, Masatsugu Tanaka, Noriko Doki, Tetsuya Eto, Hikaru Kobayashi, Yumiko Maruyama, Tatsuo Ichinohe, Junya Kanda, Yoshiko Atsuta, and Satoko Morishima
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
31. Reducing Mortality of Single-Unit Unrelated Cord Blood Transplantation for Relapsed Acute Myeloid Leukemia after a Previous Allogeneic Transplantation: A Real-World Retrospective Study Over the Past 19 Years in Japan
- Author
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Takaaki Konuma, Shohei Mizuno, Kaito Harada, Naoyuki Uchida, Satoshi Takahashi, Tetsuya Eto, Shuichi Ota, Hikaru Kobayashi, Yuta Katayama, Yasuo Mori, Yumiko Maruyama, Makoto Onizuka, Akihito Yonezawa, Toshiro Kawakita, Takafumi Kimura, Yoshinobu Kanda, Takahiro Fukuda, Yoshiko Atsuta, and Masamitsu Yanada
- Subjects
Adult ,Transplantation ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,Middle Aged ,Leukemia, Myeloid, Acute ,Japan ,Recurrence ,Molecular Medicine ,Immunology and Allergy ,Humans ,Transplantation, Homologous ,Cord Blood Stem Cell Transplantation ,Retrospective Studies - Abstract
Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). Second or subsequent allogeneic HCT using unrelated cord blood has been performed for adult patients with AML who have relapsed after a previous allogeneic HCT. Although outcomes after unrelated cord blood transplantation (CBT) as the first allogeneic HCT have significantly improved in recent years, it is unclear whether survival and engraftment improve after CBT as the second or subsequent allogeneic HCT for adult AML patients relapsing after a previous allogeneic HCT. The objective of this retrospective study was to evaluate trends of survival and other transplantation outcomes after single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT over the past 19 years in Japan. We retrospectively assessed survival trends and other outcomes of single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT according to the time period of CBT (2001-2007, 2008-2013, or 2014-2019) using a nationwide Japanese database. The median age was 45 years among 1109 CBTs, and 844 (78.6%) patients were not in complete remission at the time of CBT. Over the 3 time periods, there was a progressive increase in higher cryopreserved cord blood total nucleated cell dose and myeloablative conditioning regimens. The 2-year overall survival was 14.0% in 2001-2007, 19.9% in 2008-2013, and 24.4% in 2014-2019 (P.001 by log-rank trend test). The 2-year relapse-related mortality was 54.0% in 2001-2007, 44.4% in 2008-2013, and 39.1% in 2014-2019 (P0.001 by Gray's test), but nonrelapse mortality was not significantly different across the time periods (P = 0.557 by Gray's test). The 42-day neutrophil engraftment also significantly improved (62.9% in 2001-2007, 69.7% in 2008-2013, and 79.9% in 2014-2019; P0.001 by Gray's test). Our data demonstrate significant improvements in overall and relapse-related mortality, as well as neutrophil engraftment, after single-unit unrelated CBT as a second or subsequent allogeneic HCT for adult patients with AML relapsed after previous allogeneic HCT over the past 19 years.
- Published
- 2022
32. Adding melphalan to fludarabine and a myeloablative dose of busulfan improved survival after allogeneic hematopoietic stem cell transplantation in a propensity score-matched cohort of hematological malignancies
- Author
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Naoyuki Uchida, Masahiko Hara, Hisashi Yamamoto, Toshiro Kawakita, Yumiko Maruyama, Takahiro Fukuda, Takashi Ashida, Yoshiko Atsuta, Atsushi Wake, Takashi Ikeda, Tatsuo Ichinohe, Takayuki Ishikawa, Satoshi Morishige, Yoshimitsu Shimomura, Satoru Takada, and Minoko Takanashi
- Subjects
Male ,Oncology ,Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Propensity Score ,Busulfan ,Transplantation ,Proportional hazards model ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Fludarabine ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Cohort ,business ,Vidarabine ,030215 immunology ,medicine.drug - Abstract
Fludarabine and a myeloablative dose of busulfan (Flu/Bu4) can improve prognosis after allogeneic hematopoietic stem cell transplantation (HSCT) with melphalan (Mel). We investigated the prognostic impact of adding Mel to Flu/Bu4 by comparing between Flu/Bu4/Mel and Flu/Bu4 groups. This study included 846 propensity score (PS)-matched patients who received either Flu/Bu4/Mel (n = 423) or Flu/Bu4 (n = 423) from 2394 patients enrolled in a multicenter prospective registry, from January 2010 to December 2016. The primary endpoint (5-year overall survival [OS]), and the prognostic impact of adding Mel was evaluated using Cox regression analysis. The study population median age was 58 (interquartile 50-64) years and 61.0% were male. Patient characteristics were well-balanced between groups. Five-year OS was 34.2% (95% confidence interval [CI]: 27.3-41.1%) and 30.1% (24.8-35.6%) in the Flu/Bu4/Mel and Flu/Bu4 groups, respectively (log-rank P = 0.019). The adjusted hazard ratio of adding Mel was 0.77 (95% CI: 0.62-0.96) (P = 0.022) for the 5-year OS, and this attributed to a lower incidence of 5-year relapse (0.71, 0.56-0.90, P = 0.005) and relapse associated mortality (0.73, 0.57-0.95, P = 0.018). There was no statistical difference in 5-year non-relapse mortality between groups (log-rank P = 0.855). Flu/Bu4/Mel was associated with better 5-year OS compared to Flu/Bu4 in a PS-matched cohort after allogeneic HSCT.
- Published
- 2021
33. A Case of Necrotizing Lymphadenitis Suspected as Being Complicated by Bilateral Brachial Plexus Neuritis
- Author
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Tomomi Yoshikawa, Yayoi Tsukada, Tomokazu Yoshizaki, and Yumiko Maruyama
- Subjects
Brachial Plexus Neuritis ,medicine.medical_specialty ,Otorhinolaryngology ,business.industry ,Necrotizing lymphadenitis ,Medicine ,business ,Surgery - Published
- 2021
34. A Case of Suppurative Streptococcal Infection Complicated by Rheumatic Fever, with the Surgeon who Operated on the Abscess in the Aforementioned Patient also Developing Cellulitis of the Arm, Presumably Caused by Body Fluid Exposure during the Surgery
- Author
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Yayoi Tsukada, Tomokazu Yoshizaki, Ryotaro Nakazawa, Yumiko Maruyama, and Shoko Kojima
- Subjects
medicine.medical_specialty ,Otorhinolaryngology ,business.industry ,Cellulitis ,Body fluid exposure ,Medicine ,Rheumatic fever ,business ,medicine.disease ,Abscess ,Surgery - Published
- 2020
35. Comparable survival outcomes with haploidentical stem cell transplantation and cord blood transplantation
- Author
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Junichi Sugita, Yoshiko Atsuta, Hirohisa Nakamae, Yumiko Maruyama, Ken Ishiyama, Souichi Shiratori, Takahiro Fukuda, Mio Kurata, Naoki Shingai, Yukiyasu Ozawa, Masayoshi Masuko, Koji Nagafuji, Naoyuki Uchida, Masatsugu Tanaka, Makoto Onizuka, Junya Kanda, Takafumi Kimura, Tatsuo Ichinohe, and Takanori Teshima
- Subjects
Adult ,Transplantation ,Transplantation Conditioning ,Adolescent ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Hematology ,Middle Aged ,Young Adult ,Leukemia, Myeloid, Acute ,Recurrence ,Humans ,Cord Blood Stem Cell Transplantation ,Cyclophosphamide ,Aged ,Retrospective Studies - Abstract
HLA-haploidentical stem cell transplantation using post-transplant cyclophosphamide (PTCy-haplo) and umbilical cord blood transplantation (UCBT) are alternative to HLA-matched stem cell transplantation. We conducted a matched-pair analysis of PTCy-haplo and UCBT using the Japanese registry data. We identified 136 patients aged between 16 and 69 years who received PTCy-haplo as their first transplantation for acute leukemia or myelodysplastic syndromes. Control group included 408 UCBT recipients selected to match the PTCy-haplo group. Overall and relapse-free survival probabilities at 2 years were comparable between the PTCy-haplo and UCBT groups: 55% vs. 53% for overall survival (p = 0.46), and 47% vs. 48% for relapse-free survival (p = 0.79), respectively. The cumulative incidence of relapse was significantly higher (43% vs. 29%, respectively, p = 0.006), while the cumulative incidence of non-relapse mortality (NRM) was significantly lower (9% vs. 23%, respectively, p 0.001) in the PTCy-haplo group. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was lower in the PTCy-haplo group compared to the UCBT group (29% vs. 41%, respectively, p = 0.016), while those of grade III-IV acute GVHD and chronic GVHD were not statistically different between the two groups. Our results suggest that both PTCy-haplo and UCBT are viable alternatives to HLA-matched stem cell transplantation.
- Published
- 2022
36. Comparison of fludarabine, a myeloablative dose of busulfan, and melphalan vs conventional myeloablative conditioning regimen in patients with relapse and refractory acute myeloid leukemia in non-remission status
- Author
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Shuichi Ota, Shigeki Hirabayashi, Shohei Mizuno, Masamitsu Yanada, Takahiro Fukuda, Takafumi Kimura, Tetsuya Eto, Masahiko Hara, Masatsugu Tanaka, Yukiyasu Ozawa, Tatsuo Ichinohe, Junichi Mukae, Yoshiko Atsuta, Tadakazu Kondo, Nobuaki Nakano, Yoshimitsu Shimomura, Yumiko Maruyama, Naoyuki Uchida, Toshiro Kawakita, and Yoshinobu Kanda
- Subjects
Oncology ,Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,Graft vs Host Disease ,Refractory ,Recurrence ,Internal medicine ,medicine ,Humans ,In patient ,Busulfan ,Retrospective Studies ,Myeloablative conditioning regimen ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Fludarabine ,Leukemia, Myeloid, Acute ,business ,Vidarabine ,medicine.drug - Published
- 2021
37. Clinical practice guidelines for the diagnosis and management of acute otitis media in children-2018 update
- Author
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Haruo Takahashi, Fumiyo Kudo, Tatsuya Hayashi, Ken Kitamura, Sho Hashimoto, Hisakazu Yano, Yumiko Maruyama, Hidenobu Taiji, Shoichi Sawada, Yoshifumi Uno, Goro Takahashi, Hiromi Kojima, and Muneki Hotomi
- Subjects
medicine.medical_specialty ,Adolescent ,Acute otitis media ,Otoscopy ,Master plan ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Disease severity ,Japan ,Recurrence ,otorhinolaryngologic diseases ,Medicine ,Humans ,030223 otorhinolaryngology ,Intensive care medicine ,Child ,Watchful Waiting ,business.industry ,Recurrent acute otitis media ,Infant, Newborn ,Disease Management ,Infant ,Drug Resistance, Microbial ,General Medicine ,Anti-Bacterial Agents ,Clinical Practice ,Otitis Media ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Child, Preschool ,Practice Guidelines as Topic ,Surgery ,business - Abstract
"Clinical Practice Guidelines for the Diagnosis and Management of Acute Otitis Media in Children-2018 update (2018 Guidelines)" aim to provide appropriate recommendations about the diagnosis and management of children with acute otitis media (AOM), including recurrent acute otitis media (recurrent AOM), in children under 15 years of age. These evidence-based recommendations were created with the consensus of the subcommittee members, taking into consideration unique characteristics of bacteriology and antimicrobial susceptibilities of AOM pathogens in Japan, as well as global advances in vaccines., The subcommittee re-evaluated key clinical issues based on SCOPE (a master plan of the guidelines) and created clinical questions (CQ) about the diagnosis and management of AOM patients. A literature search of the publications from 2013 to 2016 were added to the Guidelines 2013, not only to assess the evidence on the effectiveness of vaccines, but also to provide up to date information of the bacteriology and antimicrobial susceptibilities of AOM causative pathogens in Japan., We have proposed guidelines for disease severity-based management of AOM patients, after classifying AOM severity into mild, moderate, and severe, based on age, clinical manifestations, and otoscopic findings., Precise otoscopic findings are essential for judging AOM severity, which can lead to appropriate management of AOM patients.
- Published
- 2020
38. A Case of Masticator Space Abscess Drained Nasally via a Rigid Endoscope
- Author
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Yumiko Maruyama and Yayoi Tsukada
- Subjects
Otorhinolaryngology ,business.industry ,Rigid endoscope ,Masticator space ,medicine ,Anatomy ,Abscess ,medicine.disease ,business - Published
- 2020
39. [IgG-variant Bing-Neel syndrome diagnosed by detecting MYD88 L265P mutation in the cerebrospinal fluid cells]
- Author
-
Yumiko, Maruyama, Hidekazu, Nishikii, Ryota, Matsuoka, Kenichi, Makishima, Naoki, Kurita, Manabu, Kusakabe, Yasuhisa, Yokoyama, Takayasu, Kato, Mamiko, Sakata-Yanagimoto, Naoshi, Obara, Naoya, Nakamura, and Shigeru, Chiba
- Subjects
Male ,Immunoglobulin G ,Mutation ,Myeloid Differentiation Factor 88 ,Humans ,Waldenstrom Macroglobulinemia ,Rituximab ,Aged - Abstract
Bing-Neel syndrome (BNS), which presents with a variety of neurological complications, is a rare manifestation of the lymphoplasmacytic lymphoma (LPL) and is characterized by the infiltration of LPL cells into the central nervous system. In this study, we report the case of a patient with BNS, which was confirmed by detecting MYD88 L265P mutation in the cerebrospinal fluid (CSF) cells. A 74-year-old patient was diagnosed with IgG-variant LPL. He achieved a very good partial response to the treatment with rituximab and bendamustine (RB) and was stable for over 5 years, when presenting a slowly progressive motor deficit in the lower limbs. It was difficult to confirm BNS from morphological analysis of the CSF cells. After detecting MYD88 L265P mutation in the CSF cells, he was subsequently diagnosed with BNS and treated with RB and intrathecal chemotherapy, resulting in rapid clinical improvement. With the onset of neurological manifestation during the clinical course of LPL, the detection of MYD88 L265P mutation in the CSF cells could be helpful for the diagnosis and management of BNS.
- Published
- 2021
40. Peritransplant glucocorticoids redistribute donor T cells to the bone marrow and prevent relapse after haploidentical SCT
- Author
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Tatsuo Ichinohe, Yoshiko Atsuta, Takahiro Fukuda, Katsuji Kaida, Ken Ishiyama, Simone A. Minnie, Yumiko Maruyama, Hiroyasu Ogawa, Geoffrey R. Hill, Bruce R. Blazar, Kathleen S. Ensbey, Shinichi Ishii, Satoshi Maruyama, Scott N. Furlan, Shuichiro Takahashi, Motoko Koyama, Hirohisa Nakamae, Ping Zhang, Takahide Ara, Takashi Daimon, Kazuhiro Ikegame, Luke Samson, and Takayuki Inoue
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,Bone marrow transplantation ,medicine.medical_treatment ,T-Lymphocytes ,Hematopoietic stem cell transplantation ,Mice ,Cell migration/adhesion ,Bone Marrow ,Internal medicine ,medicine ,Animals ,Humans ,Glucocorticoids ,Acute leukemia ,Transplantation ,business.industry ,Stem cell transplantation ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,General Medicine ,medicine.disease ,Leukemia ,medicine.anatomical_structure ,surgical procedures, operative ,Transplantation, Haploidentical ,Female ,Bone marrow ,business ,Glucocorticoid ,medicine.drug ,Research Article - Abstract
Patients with acute leukemia who are unable to achieve complete remission prior to allogeneic hematopoietic stem cell transplantation (SCT) have dismal outcomes with relapse rates well in excess of 60%. Haplo-identical SCT (haplo-SCT) may allow enhanced graft-versus-leukemia (GVL) effects by virtue of HLA class I/II donor-host disparities but typically requires intensive immune-suppression with post-transplant cyclophosphamide (PT-Cy) to prevent lethal graft-versus-host disease (GVHD). Here we demonstrate in preclinical models that glucocorticoid administration from day -1 to +5 inhibits alloantigen presentation by professional recipient antigen presenting cells in the gastrointestinal tract and prevents donor T-cell priming and subsequent expansion therein. In contrast, direct glucocorticoid signaling of donor T-cells promotes chemokine and integrin signatures permissive of preferential circulation and migration into the bone marrow, promoting donor T-cell residency. This results in significant reductions in GVHD whilst promoting potent GVL effects (relapse in recipients receiving glucocorticoids, vehicle or PT-Cy was 12%, 56% and 100% respectively). Intriguingly, patients with acute myeloid leukemia not in remission that received unmanipulated haplo-SCT and peri-transplant glucocorticoids also had an unexpectedly low relapse rate at 1 year (32%: 95% CI, 18%-47%) with high overall survival at 3 years (58%: 95% CI, 38-74%). These data highlight a potentially simple and effective approach to prevent relapse in patients with otherwise incurable leukemia that could be studied in prospective randomized trials.
- Published
- 2021
41. Altered effect of killer immunoglobulin-like receptor-ligand mismatch by graft versus host disease prophylaxis in cord blood transplantation
- Author
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Daishi Onai, Naoyuki Uchida, Takafumi Kimura, Masatsugu Tanaka, Satoko Morishima, Makoto Onizuka, Hikaru Kobayashi, Kazutaka Ozeki, Seitaro Terakura, Takahiro Fukuda, Hisayuki Yokoyama, Yoshiyuki Takahashi, Yoshiko Atsuta, Yukiyasu Ozawa, Masahiro Hirayama, Atsushi Wake, Yumiko Maruyama, Junya Kanda, Yuna Katsuoka, and Masashi Sawa
- Subjects
medicine.medical_specialty ,Graft vs Host Disease ,chemical and pharmacologic phenomena ,Mycophenolate ,Ligands ,Gastroenterology ,Receptors, KIR ,immune system diseases ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Transplantation ,Acute leukemia ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,medicine.disease ,Tacrolimus ,Leukemia, Myeloid, Acute ,Graft-versus-host disease ,Methotrexate ,Cord Blood Stem Cell Transplantation ,business ,medicine.drug - Abstract
The role of killer immunoglobulin-like receptor-ligand mismatch (KIR-ligand mismatch) between donors and recipients undergoing cord blood transplantation (CBT) is controversial. If each immunosuppressant differently affects natural killer (NK) cell function, the effect of KIR-ligand mismatch may be altered depending on the type of graft versus host disease (GVHD) prophylaxis. To verify this hypothesis, the difference in the effect of KIR-ligand mismatch was retrospectively assessed between patients who received CBT for acute leukemia, myelodysplastic syndrome, or chronic myeloid leukemia, as well as GVHD prophylaxis comprising tacrolimus plus methotrexate (MTX) or mycophenolate mofetil (MMF). In the MMF group (n = 1363), KIR-ligand mismatch augmented the incidence of non-relapse mortality (NRM; hazard ratio [HR], 1.40; P = 0.008), which worsened overall survival (OS; HR, 1.30, P = 0.0077). In the analysis of each KIR-ligand mismatch type, HLA-C2 mismatch had a favorable effect on relapse incidence (HR, 0.56; P = 0.0043) and OS (HR, 0.72; P = 0.037) only in the MTX group. In the MMF group, HLA-A3/A11 mismatch worsened NRM (HR, 1.93; P < 0.001) and OS (HR, 1.48; P = 0.014). These results imply that the effects of KIR-ligand mismatch differ with the type of GVHD prophylaxis and that assessing the KIR-ligand mismatch status is important for CBT.
- Published
- 2021
42. Cerebral radiation necrosis and brain abscess as delayed complications after carbon ion radiotherapy against nasal carcinoma
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Hiromichi Yamamoto, Masanori Kurimoto, Yayoi Tsukada, Kiyoshi Takagawa, and Yumiko Maruyama
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medicine.medical_specialty ,Adenoid cystic carcinoma ,medicine.medical_treatment ,lcsh:Surgery ,Radiation necrosis ,lcsh:RC346-429 ,030218 nuclear medicine & medical imaging ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Nasal carcinoma ,medicine ,Atypical trigeminal neuralgia ,Brain abscess ,Craniotomy ,lcsh:Neurology. Diseases of the nervous system ,Intracranial pressure ,business.industry ,Glasgow Coma Scale ,lcsh:RD1-811 ,medicine.disease ,Radiation therapy ,Carbon ion radiotherapy ,Surgery ,Neurology (clinical) ,Radiology ,business ,030217 neurology & neurosurgery - Abstract
A case of radiation induced delayed brain necrosis associated with bacterial brain abscess is reported. A 50-year-old Japanese man with adenoid cystic carcinoma underwent carbon ion radiotherapy and the cancer disappeared on MRI one year later. The MRI taken 30 months after the therapy showed white matter edema of the left temporal lobe suggesting a radiation injury. He suffered atypical trigeminal neuralgia at the V1 territory. He became delirious as Glasgow coma scale: 9 by increased intracranial pressure. He suffered aspiration pneumonia and sepsis. 6.5 years later, an emergent craniotomy was chosen for his increased intracranial pressure and aggravating neurological symptoms. Left temporal pole and necrotic tissues were removed and bacterial brain abscess was found. Brain abscess was managed with antibiotic drugs. His clinical symptoms improved. Concerning with brain abscess in this case, radiotherapy might break down of the blood-brain barrier and hematogenous bacterial brain abscess was formed by chance he suffered from sepsis before craniotomy. Carbon ion radiotherapy is promising treatment for nasal carcinomas, but radiation induced late complications should be cared.
- Published
- 2021
43. A Case of Ramsay Hunt Syndrome with Multiple Cranial Nerve Neuropathy
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Yayoi Tsukada and Yumiko Maruyama
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medicine.medical_specialty ,Otorhinolaryngology ,Ramsay Hunt syndrome ,business.industry ,medicine ,business ,Dermatology - Published
- 2019
44. A Case of Nonfunctional Parathyroid Cyst Diagnosed Preoperatively by Analysis of the Cyst Aspirate for Parathyroid Hormone
- Author
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Yumiko Maruyama, Shoko Kojima, Yayoi Tsukada, and Tomokazu Yoshizaki
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Pathology ,medicine.medical_specialty ,Otorhinolaryngology ,business.industry ,medicine ,Parathyroid hormone ,Cyst ,Parathyroid cyst ,business ,medicine.disease - Published
- 2019
45. Myeloablative Versus Reduced-Intensity Conditioning With Fludarabine/Busulfan for Myelodysplastic Syndrome: A Propensity Score-Matched Analysis
- Author
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Shuhei Kurosawa, Yoshimitsu Shimomura, Hidehiro Itonaga, Yuho Najima, Takeshi Kobayashi, Yukiyasu Ozawa, Yoshinobu Kanda, Shinichi Kako, Toshiro Kawakita, Ken-ichi Matsuoka, Yumiko Maruyama, Shuichi Ota, Hideyuki Nakazawa, Kazunori Imada, Takafumi Kimura, Junya Kanda, Takahiro Fukuda, Yoshiko Atsuta, and Ken Ishiyama
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Adult ,Transplantation ,Graft vs Host Disease ,Cell Biology ,Hematology ,Middle Aged ,Leukemia, Myeloid, Acute ,Myelodysplastic Syndromes ,Humans ,Molecular Medicine ,Immunology and Allergy ,Neoplasm Recurrence, Local ,Propensity Score ,Busulfan ,Vidarabine ,Retrospective Studies - Abstract
There are limited data comparing myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) and reduced-intensity conditioning with fludarabine/busulfan (Flu/Bu2) in patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed nationwide registry data and compared the outcomes of adult patients with MDS receiving Flu/Bu4 and Flu/Bu2 by propensity score (PS) matching. Patients who met the following criteria were eligible for enrollment: (1) age ≥16 years; (2) diagnosis of de novo MDS; (3) first allo-HSCT between 2006 and 2018; (4) related bone marrow transplantation (BMT) or peripheral blood stem cell transplantation from an HLA-matched donor, unrelated BMT from an HLA-matched or HLA-1 allele-mismatched donor, or unrelated cord blood transplantation; and (5) receiving Flu/Bu4 or Flu/Bu2 as a conditioning regimen. Flu/Bu4 comprised intravenous busulfan (total dose, 12.8 mg/kg) combined with fludarabine (total dose, 125-180 mg/m
- Published
- 2022
46. Single Cord Blood Transplantation Versus Unmanipulated Haploidentical Transplantation for Adults with Acute Myeloid Leukemia in Complete Remission
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Noriko Doki, Junya Kanda, Yumiko Maruyama, Takaaki Konuma, Masatsugu Tanaka, Satoshi Morishige, Seitaro Terakura, Yoshinobu Kanda, Masashi Sawa, Naoyuki Uchida, Shohei Mizuno, Kaito Harada, Kazuhiro Ikegame, Satoshi Yamasaki, Yoshimitsu Shimomura, Ken-ichi Matsuoka, Yukiyasu Ozawa, Tatsuo Ichinohe, Takafumi Kimura, Hirohisa Nakamae, Masamitsu Yanada, and Yoshiko Atsuta
- Subjects
Oncology ,Adult ,medicine.medical_specialty ,Disease ,Human leukocyte antigen ,Japan ,hemic and lymphatic diseases ,Internal medicine ,Immunology and Allergy ,Medicine ,Humans ,Cord blood transplantation ,Retrospective Studies ,Transplantation ,business.industry ,Complete remission ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Cell Biology ,Hematology ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,Cord blood ,Cohort ,Transplantation, Haploidentical ,Molecular Medicine ,Cord Blood Stem Cell Transplantation ,business - Abstract
Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative post-remission therapy for adult patients with acute myeloid leukemia (AML) in complete remission (CR). The availability of alternative human leukocyte antigen (HLA)-mismatched donors, such as cord blood and haploidentical related donors, could allow patients to receive allogeneic HCT who are without an HLA-matched sibling or unrelated donor. The use of these alternative donors is preferable for patients with advanced disease due to the rapid availability. However, comparative data for cord blood transplantation (CBT) and haploidentical related donor transplantation (haplo-HCT) are limited for adult patients with AML in CR. We sought to compare overall survival (OS); leukemia-free survival (LFS); graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS); and chronic GVHD-free, relapse-free survival (CRFS) between single-unit CBT (SCBT) and haplo-HCT recipients for adult patients with intermediate- or poor-risk AML in CR. We retrospectively analyzed and compared the results of allogeneic hematopoietic cell transplantation in 1313 adult patients with intermediate- or poor-risk AML in CR who received either SCBT (n = 1102) or unmanipulated haplo-HCT (n = 211) between 2007 and 2018 in Japan. Among the whole cohort, the cumulative incidences of neutrophil and platelet recovery were significantly lower in SCBT recipients compared with those in haplo-HCT recipients (P.001 for neutrophil, P.001 for platelet). SCBT was significantly associated with a higher incidence of grade II to IV acute GVHD and lower incidence of extensive chronic GVHD compared to haplo-HCT (P = .013 for grades II to IV acute GVHD; P = .006 for extensive chronic GVHD). Haplo-HCT recipients developed a higher incidence of cytomegalovirus (CMV) antigenemia compared to SCBT recipients (P = .004). In the multivariate analysis, there were no significant differences for grades III or IV acute GVHD (hazard ratio [HR], 1.17; 95% confidence interval [CI], .88 to 1.57; P = .26), relapse incidence (HR, 1.09; 95% CI, .76 to 1.58; P = .61), non-relapse mortality (HR, .83; 95% CI, .58 to 1.18; P = .32), OS (HR, .92; 95% CI, .70 to 1.20; P = .56), LFS (HR, .94; 95% CI, .73 to 1.21; P = .67), GRFS (HR, 1.12; 95% CI, .90 to 1.40; P = .27), or CRFS (HR, 1.15; 95% CI, .92 to 1.44; P = .19) between the two donor types. In the propensity score matching analysis, which identified 180 patients in each cohort, there were no significant differences in transplant outcomes between the two donor types, except for delayed neutrophil (P.001) and platelet recovery (P.001) and a higher incidence of grades II to IV acute GVHD (P = .052) in SCBT. SCBT and unmanipulated haplo-HCT had similar survival outcomes for adult patients with AML in CR despite the lower hematopoietic recovery and higher grade II to IV acute GVHD in SCBT recipients and the higher CMV antigenemia in haplo-HCT recipients.
- Published
- 2020
47. [Philadelphia chromosome-positive acute lymphoblastic leukemia complicated by bone marrow necrosis during consolidation chemotherapy]
- Author
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Kantaro, Ishitsuka, Naoshi, Obara, Takuya, Suyama, Ryota, Matsuoka, Yumiko, Maruyama, Tatsuhiro, Sakamoto, Manabu, Kusakabe, Takayasu, Kato, Naoki, Kurita, Hidekazu, Nishikii, Yasuhisa, Yokoyama, Mamiko, Sakata-Yanagimoto, Yuichi, Hasegawa, Atsushi, Shinagawa, and Shigeru, Chiba
- Subjects
Consolidation Chemotherapy ,Male ,Bone Marrow ,Positron Emission Tomography Computed Tomography ,Humans ,Philadelphia Chromosome ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma - Abstract
A 46-year-old man who had previously undergone open surgery for renal cell carcinoma (RCC) developed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). After the induction therapy, he achieved complete molecular remission. However, fever and bilateral buttock pain continued during the consolidation therapy. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) showed FDG accumulation in both iliac bones and in the sacrum; however, no causative diseases, including relapse of Ph-ALL and RCC, were detected. Iliac bone marrow biopsy revealed bone marrow necrosis (BMN), the etiology of which was presumed to be the leukemia itself and the therapeutic response to chemotherapy. Fever resolution and buttock pain alleviation were observed over the next months. We observed diffuse fibrosis in the bone marrow at day 162 and day 364 after cord blood transplantation. Moreover, the FDG accumulation was significantly reduced on PET-CT. BMN is not widely recognized despite its potential association with hematologic malignancies. Additional cases of BMN should be reviewed to clarify BMN etiology and clinical features.
- Published
- 2020
48. Comparison of Myeloablative Versus Reduced-Intensity Fludarabine/Busulfan Regimen in Patients with Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
- Author
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Yumiko Maruyama, Shuhei Kurosawa, Yuho Najima, Takahiro Fukuda, Yoshiko Atsuta, Yoshinobu Kanda, Yukiyasu Ozawa, Kazunori Imada, Toshiro Kawakita, Ken Ishiyama, Hideyuki Nakazawa, Takafumi Kimura, Shuichi Ota, Junya Kanda, Takeshi Kobayashi, Shinichi Kako, Hidehiro Itonaga, Yoshimitsu Shimomura, and Ken-ichi Matsuoka
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Reduced intensity ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biochemistry ,Fludarabine ,Regimen ,Internal medicine ,medicine ,In patient ,business ,Busulfan ,medicine.drug - Abstract
Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for myelodysplastic syndrome (MDS) but is associated with high non-relapse mortality (NRM). Its use was originally limited to younger patients eligible for myeloablative conditioning (MAC). Introducing reduced-intensity conditioning (RIC), such as a combination of fludarabine with reduced doses of busulfan (Flu/Bu2), increased the number of elderly patients suitable for allo-HSCT. Additionally, a combination of fludarabine and myeloablative doses of busulfan (Flu/Bu4) was developed to retain the antitumor activity of MAC and reduce the NRM to the level of RIC. However, few published reports have compared Flu/Bu4 and Flu/Bu2 in patients with MDS. We thus retrospectively performed a nationwide study to compare the outcomes of Flu/Bu4 and Flu/Bu2 in MDS patients undergoing allo-HSCT. Methods Clinical data were obtained from the Japanese Data Center for Hematopoietic Cell Transplantation. Inclusion criteria were age ≥16 years, diagnosis of de novo MDS, first allo-HSCT between 2006 and 2018, and receiving Flu/Bu4 consisted of intravenous busulfan (12.8 mg/kg) and fludarabine (125-180 mg/m 2) or Flu/Bu2 consisted of intravenous busulfan (6.4 mg/kg) and the same dose of fludarabine. Administration of anti-thymocyte globulin and low-dose total body irradiation (TBI, total dose ≤4 Gy) was permitted. Propensity score (PS)-matched analysis was performed to minimize selection bias, and the PS was calculated by logistic regression using the following factors: age, sex, hematopoietic cell transplantation-comorbidity index, French-American-British classification at diagnosis, cytogenetic risk, International Prognostic Scoring System score at diagnosis, disease status at allo-HSCT, bone marrow (BM) blasts at allo-HSCT, days from diagnosis to allo-HSCT, stem cell source, graft-versus-host disease (GVHD) prophylaxis, administration of anti-thymocyte globulin and TBI, and year of allo-HSCT. PS matching was performed at a 1:1 ratio using the nearest neighbor-matching method; caliper width was fixed at 0.2. The primary endpoint was the 3-year overall survival (OS). Results In total, 3406 patients underwent their first allo-HSCT: 447 and 256 received Flu/Bu4 and Flu/Bu2, respectively. Among them, 202 patients were assigned to each of the Flu/Bu4 and Flu/Bu2 groups after PS matching. The PS model created comparable cohorts with balanced baseline characteristics. The median age was 61 (range, 21-75) years. At the time of allo-HSCT, BM blasts were ≥5% in 273 (67.6%) patients. Regarding stem cell source, BM, peripheral blood stem cell, and cord blood was used in 268 (66.3%), 51 (12.6%), and 85 (21.0%) patients, respectively. The median follow-up period for survivors was 1117 (range, 40-3784) days. The 3-year OS rates were 44.8% (95% confidence interval [CI], 37.1-52.1%) and 46.9% (95% CI, 39.2-54.2%) in the Flu/Bu4 and Flu/Bu2 groups, respectively (P = 0.671, Figure 1A). The 3-year GVHD- and relapse-free survival rates were 28.8% (95% CI, 22.2-35.7%) and 33.0% (95% CI, 26.2-40.0%; P = 0.357, Figure 1B); the 3-year cumulative incidence of relapse, 28.9% (95% CI, 22.6-35.6%) and 30.0% (95% CI, 23.6-36.6%; P = 0.471, Figure 1C); and the 3-year cumulative incidence of NRM, 28.2% (95% CI, 21.7-35.0%) and 27.1% (95% CI, 20.6-33.9%; P = 0.597, Figure 1D) in the Flu/Bu4 and Flu/Bu2 groups, respectively. The 100-day cumulative incidence of grade II-IV acute GVHD was significantly higher in the Flu/Bu4 group than in the Flu/Bu2 group (41.7% [95% CI, 34.8-48.4%] vs. 29.3% [95% CI, 23.2-35.7%], P = 0.012, Figure 1E). The 100-day cumulative incidences of grade III-IV acute GVHD were 11.4% (95% CI, 7.5-16.3%) and 6.5% (95% CI, 3.6-10.5%; P = 0.064), while the 1-year cumulative incidences of extensive chronic GVHD were 19.5% (95% CI, 14.2-25.4%) and 15.1% in the Flu/Bu4 and Flu/Bu2 groups, respectively (95% CI, 10.5-20.6%; P = 0.196, Figure 1F). According to the findings of subgroup analyses, no patient had a favorable OS when using either of the two regimens (Figure 2). Conclusion The OS did not significantly differ between the Flu/Bu4 and Flu/Bu2 groups. While the Flu/Bu4 group was at an increased risk of acute GVHD, the relapse was not significantly different between the two groups. Data from more patients are needed to determine the optimal intensity of conditioning regimens in patients with MDS. Figure 1 Figure 1. Disclosures Kanda: Sanofi: Research Funding; MSD: Honoraria; Otsuka Pharmaceutical: Honoraria, Research Funding. Kako: Novartis Pharma K.K.: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Sanofi K.K.: Honoraria; Bristol-Myers Squibb/Celgene K.K.: Honoraria; Meiji Seika Pharma Co., Ltd.: Honoraria; Kyowa Hakko Kirin Co., Ltd.: Honoraria; Pfizer Japan Inc.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Fuji Pharma Co., Ltd.: Honoraria; CSL Behring K.K.: Honoraria; Amgen K.K.: Honoraria; Takeda Pharmaceutical Co., Ltd.: Honoraria. Imada: Novartis Pharma K.K.: Honoraria; Takeda Pharmaceutical Co. Ltd.: Honoraria; Otsuka Pharmaceutical Co. Ltd.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; Bristol-Myers Squibb K.K.: Honoraria; Celgene Co., Ltd.: Honoraria. Kanda: Astellas Pharma Inc.: Consultancy, Honoraria; Bristol-Myers Squibb Co: Honoraria; CHUGAI PHARMACEUTICAL Co., Ltd.: Honoraria; DAIICHI SANKYO Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Research Funding; Janssen Pharmaceutical K.K.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co., Ltd.: Honoraria; Megakaryon Co: Honoraria, Membership on an entity's Board of Directors or advisory committees; NextGeM Inc: Patents & Royalties; Novartis Pharma K.K.: Honoraria; Ono Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Sanofi K.K.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; SymBio Pharmaceuticals, Ltd.: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Company Limited: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen Astellas BioPharma: Honoraria; TEIJIN PHARMA LIMITED.: Honoraria. Atsuta: Mochida Pharmaceutical Co., Ltd.: Speakers Bureau; Astellas Pharma Inc.: Speakers Bureau; AbbVie GK: Speakers Bureau; Kyowa Kirin Co., Ltd: Honoraria; Meiji Seika Pharma Co, Ltd.: Honoraria.
- Published
- 2021
49. Randomized controlled trial of juzen-taiho-to in children with recurrent acute otitis media
- Author
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Ken Kitamura, Hideki Origasa, Toshimitsu Kobayashi, Haruo Takahashi, Noboru Yamanaka, Tomokazu Yoshizaki, Yumiko Maruyama, Makoto Ito, and Yasuaki Harabuchi
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Juzen taiho to ,medicine.drug_class ,Antibiotics ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Randomized controlled trial ,Recurrence ,law ,otorhinolaryngologic diseases ,Humans ,Medicine ,030212 general & internal medicine ,Beneficial effects ,Respiratory tract infections ,business.industry ,Recurrent acute otitis media ,Infant ,Treatment options ,General Medicine ,Middle Ear Ventilation ,Anti-Bacterial Agents ,Otitis Media ,Otorhinolaryngology ,Child, Preschool ,Acute Disease ,Female ,Surgery ,Mitogens ,business ,030217 neurology & neurosurgery ,Drugs, Chinese Herbal - Abstract
Objective Recurrent acute otitis media (AOM) in young children is rapidly increasing worldwide. Repeated antibiotic use leads to antibiotic-resistant pathogen development. Complementary and alternative medicine approaches have been suggested as a supplemental treatment option to conventional antimicrobial medicine. This randomized, parallel-group, open-label, non-herbal medicine controlled trial assessed the efficacy of a traditional Japanese herbal medicine, juzen-taiho-to (JTT) for AOM prevention in otitis-prone children. Methods Children prone to recurrent AOM aged 6–48 months were recruited from 26 otolaryngology clinics in Japan and received conventional AOM treatment based on Japanese guidelines with or without 2 daily oral doses of JTT (0.10–0.25 g/kg/day). The mean number of AOM episodes, coryza episodes, and duration of total antibiotic administration per month were compared during 3-month intervention. Results At least one episode of AOM was diagnosed in 71% of JTT-group and 92% of control participants during follow-up. JTT administration reduced the frequency of AOM episodes by 57% compared with children who received conventional treatment alone (0.61 ± 0.54 vs. 1.07 ± 0.72 AOM instances/month; P = 0.005) and also significantly decreased number of coryza episodes ( P = 0.015) and total antibiotic administration ( P = 0.024). Conclusions This is the first report of recurrent AOM prevention by herbal medication. JTT appears to effectively prevent recurrent AOM in children. Subsequent double-blind studies are needed to confirm the beneficial effects of JTT on recurrent AOM and upper respiratory tract infections.
- Published
- 2017
50. [Fatal exacerbations of chronic active Epstein-Barr virus infection subsequent to cytotoxic chemotherapy]
- Author
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Sakurako, Suma, Naoki, Kurita, Naoko, Baba, Kantaro, Ishitsuka, Shinichiro, Sukegawa, Kenichi, Makishima, Yusuke, Kiyoki, Yumiko, Maruyama, Takayasu, Kato, Yasuhisa, Yokoyama, Mamiko, Sakata-Yanagimoto, Naoshi, Obara, Yuichi, Hasegawa, and Shigeru, Chiba
- Subjects
Adult ,Male ,Epstein-Barr Virus Infections ,Fatal Outcome ,Transplantation Conditioning ,Recurrence ,Multiple Organ Failure ,Chronic Disease ,Hematopoietic Stem Cell Transplantation ,Humans ,Female ,Middle Aged ,Lymphohistiocytosis, Hemophagocytic - Abstract
Chronic active Epstein-Barr virus infection (CAEBV) is critical owing to lethal complications such as hemophagocytic lymphohistiocytosis (HLH), multiple organ failure, and malignant lymphoma. Here we present two cases of CAEBV who developed rapid and life-threatening disease progression after cytotoxic chemotherapy. Case 1: In a 34-year-old male, CAEBV recurred after 4-month remission obtained by initial therapy with etoposide, cyclosporine, and prednisolone. Accordingly, cord blood transplantation was planned. A day after administering high-dose melphalan as the conditioning, he developed respiratory failure, pancytopenia, and hyperferritinemia. He died 3 days later. Case 2: A 53-year-old female attained remission after initial therapy for CAEBV. After 1 month, she relapsed, and high-dose cytarabine (HDAC) was administered. A day after HDAC administration, she suddenly developed respiratory failure, which was followed by multiple organ failure. She died 3 days later. Thus, planned strategy for prompt allogeneic hematopoietic stem cell transplantation is necessary to prevent disease progression and control cytokinemia before cytotoxic chemotherapy for CAEBV.
- Published
- 2019
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