Researchers Database

fujiwara shinichirou

    DivisionofCellTransplantationandTransfusion Professor
Last Updated :2021/12/07

Researcher Information

URL

J-Global ID

Research Interests

  • 癌遺伝子   抗原発現   悪性リンパ腫   CD25   

Research Areas

  • Life sciences / Hematology and oncology
  • Other / Other / Laboratory medicine

Academic & Professional Experience

  • 2009 - 2011  Jichi Medical UniversitySchool of Medicine助教

Published Papers

  • Umino K, Fujiwara SI, Ikeda T, Kawaguchi SI, Toda Y, Ito S, Ochi SI, Nagayama T, Mashima K, Minakata D, Nakano H, Yamasaki R, Morita K, Kawasaki Y, Yamamoto C, Ashizawa M, Hatano K, Sato K, Oh I, Ohmine K, Muroi K, Kanda Y
    Leukemia & lymphoma 60 (8) 1 - 8 1042-8194 2019/04 [Refereed][Not invited]
     
    This study sought to investigate the impact of the soluble interleukin-2 receptor level in the relapsed or refractory phase (r/r sIL-2R) on the clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL). We determined the optimal cutoff value of r/r sIL-2R for disease progression within 6 months from salvage chemotherapy to be 861 U/mL. The high r/r sIL-2R group exhibited a significantly lower survival rate than the low r/r sIL-2R group (1-year event-free survival [EFS], 22.6% vs. 55.7%, p < .001 and 1-year overall survival [OS], 45.9% vs. 75.1%, p < .001). Independent significant correlations were observed between r/r sIL-2R and both inferior 1-year EFS and OS in a multivariate analysis (hazard ratio [HR]: 2.69, 95% CI: 1.61-4.51, p < .001 and HR: 2.99, 95% CI: 1.57-5.70, p < .001). This study demonstrates that r/r sIL-2R could be useful for predicting a poor prognosis in patients with r/r DLBCL.
  • Umino K, Fujiwara SI, Minakata D, Yamamoto C, Meguro A, Matsuyama T, Sato K, Ohmine K, Izumi T, Muroi K, Kanda Y
    Leukemia & lymphoma 60 (3) 734 - 741 1042-8194 2019/03 [Refereed][Not invited]
  • Fujiwara SI, Ikeda T, Morita K, Shinzato T, Ishikawa N, Nakamura N, Yagisawa T, Kanda Y
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 19 (8) 2374 - 2377 1600-6135 2019/03 [Refereed][Not invited]
     
    Patients who undergo kidney transplantation are at increased risk of cancer due to the long-term use of immunosuppressive treatment. Postrenal transplant cancers usually originate from recipient cells, but donor-related cancers have been rarely reported. We report the case of 49-year-old woman who developed multiple myeloma of donor origin 7 years after kidney transplantation. The donor was the mother of the recipient and also developed multiple myeloma 1 year after kidney donation. The diagnosis of multiple myeloma was based on IgG lambda monoclonal protein and the infiltration of plasma cells in bone marrow. The renal biopsy did not reveal plasmacytoma in the transplanted kidney. Epstein-Barr virus DNA load was negative in peripheral blood. The patient responded to lenalidomide and dexamethasone, and subsequently received autologous stem cell transplantation. Donor chimerism was detected in the recipient marrow by short tandem repeat analysis; however, studies of Ig gene rearrangement were inconclusive due to insufficient DNA quality. The chromosomal abnormalities in the two myelomas were different. This case suggests that donor cells with myeloma-initiating potential can be transferred to a recipient via a renal graft and can lead to the development of donor-derived multiple myeloma in the recipient under immunosuppression.
  • Minakata D, Fujiwara SI, Ikeda T, Kawaguchi SI, Toda Y, Ito S, Ochi SI, Nagayama T, Mashima K, Umino K, Nakano H, Yamasaki R, Morita K, Kawasaki Y, Sugimoto M, Yamamoto C, Ashizawa M, Hatano K, Sato K, Oh I, Ohmine K, Muroi K, Ohmori T, Kanda Y
    International journal of hematology 109 (2) 141 - 146 0925-5710 2019/02 [Refereed][Not invited]
     
    We evaluated clinical outcomes of disseminated intravascular coagulation (DIC) in patients with hematological malignancies treated with synthetic protease inhibitors (SPIs) and compared the effects of gabexate mesilate (FOY) and nafamostat mesilate (FUT). We retrospectively examined 127 patients [acute myeloid leukemia (n = 48), acute lymphoblastic leukemia (n = 25), and non-Hodgkin lymphoma (n = 54)] with DIC, who were diagnosed according to Japanese Ministry of Health, Labour and Welfare criteria and treated with SPIs [FOY (n = 55) and FUT (n = 72)] at our hospital from 2006 to 2015. The DIC resolution rates on days 7 and 14 were 42.6% and 62.4%, respectively. No significant differences were observed in DIC resolution rates between the FUT and FOY groups [40.3% vs. 45.5% (day 7), P = 0.586; 56.3% vs. 69.8% (day 14), P = 0.179, respectively]. Multivariate analysis revealed that response to chemotherapy was the only independent predictor of DIC resolution on days 7 and 14 (ORR 2.81, 95% CI 1.32-5.98, P = 0.007; ORR 2.51, 95% CI 1.12-5.65, P = 0.026). Resolution of DIC was correlated with improvement of background hematological malignancies, and no significant differences were observed between the two SPIs.
  • Fujiwara SI, Kanda J, Tatara R, Ogawa H, Fukuda T, Okumura H, Ohashi K, Iwato K, Ueda Y, Ishiyama K, Eto T, Matsuoka KI, Nakamae H, Onizuka M, Atsuta Y, Kanda Y, HLA Working, Group of, the Japan, Society for, Hematopoietic Cell Transplantation
    Bone marrow transplantation 54 (8) 1327 - 1336 0268-3369 2019/01 [Refereed][Not invited]
     
    The significance of low-dose total body irradiation (TBI) in HLA-mismatched reduced-intensity conditioning stem cell transplantation (RICT) remains unknown. We, retrospectively, evaluated the impact of low-dose TBI in patients with hematological malignancies who received first RICT from ≥1 antigen-mismatched donors between 2004 and 2014. Of the 575 patients, 361 patients received low-dose TBI (2 or 4 Gy). There were no significant differences in neutrophil engraftment or platelet recovery between TBI and non-TBI groups. The benefit of low-dose TBI on neutrophil engraftment was not observed in any subgroups. Low-dose TBI was not associated with decreased secondary graft failure. Suppressed mixed chimerism and autologous hematopoiesis by low-dose TBI was observed. There were no significant differences in cumulative incidences of acute GVHD or nonrelapse mortality rates in either group; however, low-dose TBI improved overall survival (OS), especially in patients with high-risk disease, multi-HLA mismatch, and fludarabine/busulfan conditioning. Multivariate analysis demonstrated that low-dose TBI was an independent prognostic factor for OS. Compared with the non-TBI group, 4 Gy TBI, but not 2 Gy TBI, was associated with increased acute GVHD and reduced relapse. These findings suggest that low-dose TBI may be beneficial for patients at high risk for relapse in HLA-mismatched RICT.
  • Morita K, Fujiwara SI, Ikeda T, Kawaguchi SI, Toda Y, Ito S, Ochi SI, Nagayama T, Mashima K, Umino K, Minakata D, Nakano H, Yamasaki R, Kawasaki Y, Sugimoto M, Ashizawa M, Yamamoto C, Hatano K, Sato K, Oh I, Ohmine K, Muroi K, Ashizawa K, Yamamoto Y, Oshiro H, Kanda Y
    Acta haematologica 141 (3) 158 - 163 0001-5792 2019 [Refereed][Not invited]
     
    TAFRO syndrome, a rare systemic inflammatory disease, can lead to multiorgan failure without appropriate treatment. Although thrombocytopenia is frequently seen in patients with TAFRO syndrome, little is known about its pathogenesis. Moreover, while recent studies have reported the presence of an anterior mediastinal mass in some patients, the pathological status of this remains unclear. Here, we report a case of fatal bleeding in a patient with TAFRO syndrome accompanied by an anterior mediastinal mass. A 55-year-old female was transferred to our hospital with a 2-week history of fever, epistaxis, and dyspnea. Laboratory tests revealed severe thrombocytopenia, computed tomography (CT) showed pleural effusions, and bone marrow biopsy revealed reticulin myelofibrosis. We suspected TAFRO syndrome, but the CT scan showed an anterior mediastinal mass that required a biopsy to exclude malignancy. She soon developed severe hemorrhagic diathesis and died of intracranial hemorrhage despite intensive treatment. She had multiple autoantibodies against platelets, which caused platelet destruction. An autopsy of the mediastinal mass revealed fibrous thymus tissues with infiltration by plasma cells. Our case suggests that thrombocytopenia could be attributed to antibody-mediated destruction and could be lethal. Hence, immediate treatment is imperative in cases of severe thrombocytopenia, even when accompanied by an anterior mediastinal mass.
  • Fujiwara SI, Fujishima N, Kanamori H, Ito M, Sugimoto T, Saito S, Sakaguchi T, Nagai K, Masuoka H, Nagai K, Morita A, Kino S, Tanaka A, Hasegawa Y, Yokohama A, Fujino K, Makino S, Matsumoto M, Takeshita A, Muroi K
    Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 57 (6) 746 - 751 1473-0502 2018/12 [Refereed][Not invited]
  • Umino K, Fujiwara SI, Ikeda T, Toda Y, Ito S, Mashima K, Minakata D, Nakano H, Yamasaki R, Kawasaki Y, Sugimoto M, Yamamoto C, Ashizawa M, Hatano K, Sato K, Oh I, Ohmine K, Muroi K, Kanda Y
    Hematology (Amsterdam, Netherlands) 23 (8) 470 - 477 1024-5332 2018/09 [Refereed][Not invited]
  • Shin-ichiro Fujiwara, Yuya Shirato, Takashi Ikeda, Shin-ichiro Kawaguchi, Yumiko Toda, Shoko Ito, Shin-ichi Ochi, Takashi Nagayama, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Hirofumi Nakano, Kaoru Morita, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
    International Journal of Hematology 107 (6) 712 - 715 1865-3774 2018/06 [Refereed][Not invited]
     
    Tyrosine kinase inhibitors (TKIs) are standard therapy for chronic myeloid leukemia (CML). However, the effects of these agents on mature B cell lymphoma are not well known. We describe a 50-year-old man who was diagnosed with CML in the chronic phase and treated with imatinib. After 3 years of imatinib therapy that achieved a complete cytogenetic response of CML, he developed Philadelphia-negative follicular lymphoma (FL). Rituximab monotherapy induced a partial response of FL, and he subsequently achieved a major molecular response (MMR) of CML. Three years later, however, the MMR was lost, followed by the progression of FL. Imatinib was switched to nilotinib for the treatment of CML, while we chose watchful waiting for FL. He achieved MMR again under treatment with nilotinib for 8 months including one month of substitutional use of dasatinib due to adverse events, but thereafter nilotinib was switched to bosutinib due to hyperbilirubinemia. With the administration of second-generation TKIs (2G-TKIs) for a total of 18 months, he achieved a complete response to FL without antilymphoma treatment. This is the first report to suggest that 2G-TKIs may have direct or indirect effects on FL.
  • Shinichi Kako, Shinichiro Fujiwara, Miki Sato, Shun-ichi Kimura, Hideki Nakasone, Kazuteru Ohashi, Toshiro Kawakita, Tetsuo Maeda, Takanobu Morishita, Ritsuro Suzuki, Takahiro Fukuda, Tatsuo Ichinohe, Mio Kurata, Yoshiko Atsuta, Yoshinobu Kanda
    Biology of Blood and Marrow Transplantation 24 (10) 2139 - 2144 1523-6536 2018 [Refereed][Not invited]
     
    Compared with 4-times-daily infusion of intravenous busulfan (ivBU4), the safety and efficacy of once-daily infusion of ivBU (ivBU1) has not been fully clarified. We have been routinely using ivBU1 in a conditioning regimen in adult patients with myeloid malignancy who undergo allogeneic hematopoietic stem cell transplantation. In this study, a total of 91 patients who received ivBU1 for 2 days (n = 18) or 4 days (n = 73) in our institutions were compared with 273 control patients who received ivBU4, who were matched for age, sex, performance status, disease risk, conditioning regimen, and donor type, selected from the database of the Japanese Society for Hematopoietic Cell Transplantation using optimal matching algorithms. One-year overall survival (56.8% versus 57.1%, P =.94), disease-free survival (51.6% versus 50.8%, P =.73), relapse rate (28.5% versus 26.2%, P =.94), nonrelapse mortality (19.9% versus 23.0%, P =.71), and the incidence of graft-versus-host disease were not significantly different between the ivBU1 and ivBU4 groups. In patients who received ivBU1, neutrophil recovery was slower (median days: 22 versus 17, P =.001), and the incidence of veno-occlusive disease was lower (2.6% versus 17.4%, P =.04). In conclusion, ivBU1 can be safely administered with clinical outcomes similar to those with ivBU4.
  • Shin-ichiro Fujiwara, Shuichi Kino, Asashi Tanaka, Yuichi Hasegawa, Akihiko Yokohama, Keizo Fujino, Makino Shigeyoshi, Mayumi Matsumoto, Akihiro Takeshita, Kazuo Muroi
    TRANSFUSION AND APHERESIS SCIENCE 56 (5) 708 - 712 1473-0502 2017/10 [Refereed][Not invited]
     
    Background: Premedication before transfusion is commonly administered in clinical practice despite a lack of evidence for its efficacy. The aim of this study was to clarify the status of premedication and evaluate expert opinions regarding its use in Japanese medical institutions. Method: Between May and July 2016, we conducted a questionnaire survey on premedication before transfusion in 252 medical institutes that were certified by an academic society or employed transfusion experts. Results: A total of 141 institutes (54.2%) responded, and hematologists (n = 113) comprised the most frequent respondents. The purpose of premedication was to prevent urticaria, pruritus, and fever, and washed blood products were used for anaphylactic shock or refractory transfusion reactions before. Drugs for premedication were intravenously administered either just before or 30 min before transfusion. Both inpatients and outpatients were premedicated in a similar manner, and institutional guidelines were not established. More than half of the experts recognized premedication as efficient and necessary, and premedication for previous transfusion reactions was frequently implemented, particularly for platelet transfusion or in patients with hematological diseases. Some institutions administered one or more drugs for premedication from the first transfusion. Antihistamines and hydrocortisone were the most frequently used as premedication. Conclusion: Our study reports the current status of premedication for transfusion in Japan. Antihistamines and hydrocortisone were most commonly used for premedication despite a lack of evidence of their use. These findings may help clarify the indications for premedication and the use of washed blood products. (C) 2017 Elsevier Ltd. All rights reserved.
  • Hirofumi Nakano, Shin-ichiro Fujiwara, Shoko Ito, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi, Yoshinobu Kanda
    HEMATOLOGICAL ONCOLOGY 35 (3) 357 - 364 0278-0232 2017/09 [Refereed][Not invited]
     
    The early clearance of blast cells in peripheral blood (PB) during induction chemotherapy can predict the clinical outcome in acute leukemia. We retrospectively analyzed the kinetics of white blood cell (WBC) count, blast cell percentage (BCP), and blast cell count (BCC) in PB in 78 patients with de novo acute myeloid leukemia who underwent a uniform induction chemotherapy between December 2001 and December 2015 at Jichi Medical University. By a repeated-measures analysis of variance, the interaction of the decline in BCP with the achievement of complete remission (CR) was stronger than those of the decline in WBC or BCC. A receiver operating characteristic curve analysis for the achievement of CR showed that the areas under the curve for the decline in WBC, BCP, and BCC were 0.592, 0.703, and 0.634, respectively, and a decline in BCP of 9.25%/day within 4 or 5days from induction chemotherapy was the optimal cutoff value. A multivariate analysis showed that a rapid decline in BCP (9.25%/day) was a significant predictive factor for CR, independent of the cytogenetic risk (p=0.0096). A rapid decline in BCP during the first 5days of induction chemotherapy may be a good predictor of CR. Copyright (c) 2015 John Wiley & Sons, Ltd.
  • Daisuke Minakata, Shin-ichiro Fujiwara, Takashi Ikeda, Yumiko Toda, Shoko Ito, Kiyomi Mashima, Kento Umino, Hirofumi Nakano, Ryoko Yamasaki, Kaoru Morita, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
    INTERNATIONAL JOURNAL OF HEMATOLOGY 106 (3) 411 - 417 0925-5710 2017/09 [Refereed][Not invited]
     
    We retrospectively analyzed the relationship between white blood cell (WBC) count elevation after priming and clinical response in 115 patients with AML (61 untreated and 54 relapsed or refractory) treated with low-dose cytarabine, aclarubicin, and G-CSF priming. Receiver operating characteristic curve analysis showed that the ratio of maximum WBC count to pretreatment WBC count (WBCratio) was most strongly associated with complete remission (CR) in previously untreated patients among several parameters we analyzed in this study; however, the prediction accuracy was not clinically significant considering the area under the curve of 0.694. Based on the cutoff value of the WBCratio, CR rate and event-free survival in the high WBCratio group were significantly better than those in the low WBCratio group in untreated patients. Regarding the WBC differential counts, a high ratio of the maximum to pretreatment value of neutrophils rather than that of peripheral blasts was associated with a superior CR rate. In addition, an increase in blasts after G-CSF priming had a significant negative impact on CR rate in untreated patients. In conclusion, an increase in blast counts after G-CSF priming was not predictive of achieving CR.
  • Shoko Ito, Shin-ichiro Fujiwara, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi, Yoshinobu Kanda
    ANNALS OF HEMATOLOGY 96 (5) 719 - 724 0939-5555 2017/05 [Refereed][Not invited]
     
    The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4.2 years. Diagnosis of AML and CLL was made simultaneously in 16 patients. The CR rate of AML was 42.9%, and the median survival was only 1.5 months after the diagnosis of AML. Patients who achieved CR tended to survive longer than those who did not. Our results demonstrated that the development of AML in patients with untreated CLL was associated with a poor response to chemotherapy and an extremely poor prognosis.
  • Umino K, Fujiwara SI, Ikeda T, Toda Y, Ito S, Mashima K, Minakata D, Nakano H, Yamasaki R, Kawasaki Y, Sugimoto M, Yamamoto C, Ashizawa M, Hatano K, Sato K, Oh I, Ohmine K, Muroi K, Kanda Y
    Hematology (Amsterdam, Netherlands) 22 (9) 1 - 6 1024-5332 2017/04 [Refereed][Not invited]
  • Kento Umino, Shin-Ichiro Fujiwara, Shoko Ito, Kiyomi Mashima, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Masahiro Ashizawa, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi, Yoshinobu Kanda
    LEUKEMIA & LYMPHOMA 58 (2) 316 - 323 1042-8194 2017/02 [Refereed][Not invited]
     
    We evaluated 121 patients with follicular lymphoma (FL) and analyzed the association between the soluble interleukin-2 receptor (sIL-2R) level at diagnosis and the cumulative incidence of transformation. By a receiver-operating characteristic analysis, we determined a cutoff value of sIL-2R for transformation at 4360U/mL to classify patients into two groups. Patients in the high sIL-2R group showed a shorter progression-free survival (PFS) and shorter disease-specific survival (DSS) (p<0.001 and p=0.018). Furthermore, the cumulative incidence of transformation in the high sIL-2R group was higher than that in the low sIL-2R group (40.9% vs. 7.3% at 5 years, p<0.001). In a multivariate analysis, high sIL-2R was an independent predictive risk factor for transformation (HR 7.42, 95% CI: 2.75-20.0, p<0.001). This study showed that the sIL-2R level at diagnosis may be a prognostic factor for transformation, PFS, and DSS in patients with FL.
  • Shin-ichiro Fujiwara, Kazuo Muroi, Chihiro Yamamoto, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Keiya Ozawa
    HEMATOLOGY 22 (6) 347 - 353 1024-5332 2017 [Refereed][Not invited]
     
    Objectives: CD25 has been reported to be highly expressed in leukemia stem cells and correlated with adverse outcomes in young patients with acute myeloid leukemia (AML). However, the significance of CD25 expression in elderly patients with AML has not yet been investigated. Methods: We retrospectively analyzed 154 newly diagnosed AML patients aged 60 years or over by flow cytometry. Results: CD25-positive AML was characterized by high white blood cell counts, secondary AML, rare favorable karyotypes, and positivity for CD34 and CD7 antigens, compared with CD25-negative AML. CD25 positivity was significantly correlated with an inferior complete remission (CR), event-free survival (EFS), and overall survival. Multivariate analysis showed CD25 positivity to be a significant prognostic predictor of CR and EFS. A regimen of low-dose cytarabine and aclarubicin combined with granulocyte-colony-stimulating factor (CAG) led to higher CR rates in the CD25-positive AML patients than intensive chemotherapies. CD25 expression was increased at relapse and in the development of leukemic status from myelodysplastic syndrome or myeloproliferative neoplasm. Discussion: An effective treatment strategy for elderly patients with CD25-positive AML has not been established. Further studies are needed to evaluate the effect of a CAG regimen and allogenic stem cell transplantation in patients. Conclusion: CD25 is an independent prognostic factor in elderly AML patients. Alternative therapies for CD25-positive elderly AML patients are needed.
  • Kento Umino, Shin-ichiro Fujiwara, Kazuya Sato, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Kaoru Hatano, Kiyoshi Okazuka, Lekuni Oh, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi, Yoshinobu Kanda
    ACTA HAEMATOLOGICA 137 (2) 93 - 99 0001-5792 2017 [Refereed][Not invited]
     
    The prognosis of patients with systemic lymphoma with central nervous system (CNS) involvement is very poor and there is no established standard therapy. We retrospectively analyzed 18 patients (4 untreated and 14 relapsed) with systemic lymphoma with CNS involvement who received methotrexate and cytarabine-based multiagent chemotherapy (modified Bonn protocol). Complete and partial responses were achieved in 56 and 22% of the patients, respectively. The 1-year overall survival (OS) and progression-free survival (PFS) was 81.0 and 39.2%, respectively. Patients with parenchymal involvement showed a better 1-year PFS than those with either leptomeningeal involvement or both. In a multivariate analysis, poor performance status (PS) was the only independent prognostic factor for the 1-year OS and PFS (HR 10.8, 95% CI 1.09-108, p = 0.042; HR 20.8, 95% CI 2.39-181, p = 0.006, respectively). Grade 4 neutropenia and thrombocytopenia occurred in 17 patients each (94%), but there were no grade 4 nonhematopoietic adverse events. The modified Bonn pro-tocol resulted in relatively favorable response and survival, and provided clinical benefits to patients with good PS, in particular. This study demonstrated that the modified Bonn protocol could be a feasible and encouraging treatment approach for lymphoma with CNS and systemic involvement. (C) 2017 S. Karger AG, Basel
  • Chihiro Yamamoto, Shoko Ito, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Hirofumi Nakano, Masahiro Ashizawa, Kiyoshi Okazuka, Kaoru Hatano, Kazuya Sato, Lekuni Oh, Shin-Ichiro Fujiwara, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi, Yoshinobu Kanda
    LEUKEMIA & LYMPHOMA 57 (11) 2541 - 2547 1042-8194 2016/11 [Refereed][Not invited]
     
    The combination of mitoxantrone (MIT), etoposide (ETP), and cytarabine (Ara-C) (MEC) is a frequently used salvage therapy for acute leukemia, but has been associated with severe myelosuppression. Therefore, we investigated the miniMEC regimen with reduced doses of AraC and MIT. Thirteen ALL and 44 AML patients, all relapsed or refractory, received miniMEC, which consisted of MIT at 8 mg/m(2) for 3 d, ETP at 100 mg/m(2) for 5 d, and Ara-C at 100 mg/m(2) infused over 24 h for 7 d. CR + CRi was achieved in eight ALL patients (61.5%) and 16 AML patients (36.4%). Median duration of neutropenia was 30 d (range, 1-50). Thirty-one patients (54.4%) subsequently received allogeneic stem cell transplantation (SCT), and overall survival was significantly improved in this group (median OS 161 versus 481 d, p=0.006). We concluded that miniMEC is a safe and effective bridging therapy to SCT.
  • Kazuhiko Ikeda, Keiji Minakawa, Kazuo Muroi, Shin-ichiro Fujiwara, Minami Yamada-Fujiwara, Yoshihiro Fujimori, Ryuji Tanosaki, Hitoshi Ohto
    TRANSFUSION 56 (11) 2839 - 2847 0041-1132 2016/11 [Refereed][Not invited]
     
    BACKGROUND: Improving apheresis technology may lead to an efficient and safe peripheral blood stem cell (PBSC) collection. Recently, the Spectra Optia (Optia, Terumo BCT) was introduced as an automated apheresis instrument, but comparisons with other instruments have been few. This is the first randomized multicenter and crossover comparison of the Optia with the automated program of the established apheresis instrument, the Spectra (Spectra-Auto, Terumo BCT). STUDY DESIGN AND METHODS: A total of 233 apheresis procedures performed in 46 autologous patients and 108 allogeneic donors were investigated. Apheresis performed in the first day for all subjects using the Spectra-Auto (n = 79) and the Optia (n = 75) were evaluated as first-day analysis. Seventy-nine subjects, who required another session on the second day, underwent apheresis using the other instrument than the first-day instrument and were compared with each other in a paired crossover analysis. RESULTS: The two instruments processed similar volumes with comparable run times and volumes of acid-citrate-dextrose used. The volumes of collected products were greater in the Optia. Yields of mononuclear cells and CD34+ cells were not different, but collection efficiencies were higher in the Optia (p = 0.008 in CE1 of crossover analysis). Spectra-Auto-collected products contained more contaminating red blood cells (RBCs), whereas there was a trend of more contaminating platelets (PLTs) in the Optia-collected products. Slight reductions were noted in the RBC or PLT counts of subjects who underwent apheresis with the Spectra-Auto or the Optia, respectively. CONCLUSION: The Optia is safe and more efficient in the PBSC collection compared with the Spectra-Auto.
  • Takahiro Suzuki, Hiroyuki Kobayashi, Yasufumi Kawasaki, Kiyoshi Okazuka, Kaoru Hatano, Shin-ichiro Fujiwara, Iekuni Oh, Ken Ohmine, Yoshinobu Kanda
    INTERNATIONAL JOURNAL OF HEMATOLOGY 104 (4) 446 - 453 0925-5710 2016/10 [Refereed][Not invited]
     
    Anti-thymocyte globulin (ATG) is a key drug in immunosuppressive therapy for patients with aplastic anemia. The mainstay of ATG therapy had been a horse ATG (hATG) formulation, Lymphoglobulin or ATGAM, but Lymphoglobulin was recently discontinued, and Thymoglobulin, a rabbit ATG (rATG) formulation, is currently used as the first-line drug in many countries, including Japan. However, a recent randomized clinical trial reported significantly unfavorable outcomes associated with the use of rATG regimens. We retrospectively analyzed clinical outcomes of adult patients with moderate to severe aplastic anemia who were treated with 3.5 mg/kg of Thymoglobulin (n = 22) or 15 mg/kg of Lymphoglobulin (n = 25) in our facility. The estimated overall response rates in the rATG and hATG groups were 64.6 versus 56.0 % at 6 months, and 76.4 versus 69.2 % at 12 months, respectively; and there was no statistical difference between the two groups (P = 0.32). Overall survival at 24 months was not significantly different: rATG 89.8 % versus hATG 96.0 % (P = 0.39). Early phase infection was observed in 37.5 % of cases in the rATG and 14.8 % in the hATG group, but the frequency was not statistically different (P = 0.107). Our data indicate that Thymoglobulin at a dose of 3.5 mg/kg is a viable alternative when hATG is not available.
  • Yoshinobu Maeda, Hisakazu Nishimori, Yoshihiro Inamoto, Hirohisa Nakamae, Masashi Sawa, Yasuo Mori, Kazuteru Ohashi, Shin-Ichiro Fujiwara, Mitsune Tanimoto
    ACTA MEDICA OKAYAMA 70 (5) 409 - 412 0386-300X 2016/10 [Refereed][Not invited]
     
    Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HSCT). Retinoic acid (tamibarotene) exerts multiple effects on cell differentiation and is clinically used for the treatment of acute promyelocytic leukemia. Tamibarotene down-regulates both Th1 and Th17 differentiation in donor T cells after allogeneic HSCT, resulting in attenuation of experimental chronic GVHD. Based on preclinical data, we have launched a phase II study of tamibarotene in patients with steroid-refractory chronic GVHD. This study will clarify whether tamibarotene can exert beneficial effects in patients with steroid-refractory chronic GVHD.
  • Miyuki Sugimoto, Shoko Ito, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Masahiro Ashizawa, Chihiro Yamamoto, Shin-ichiro Fujiwara, Kiyoshi Okazuka, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi, Shinichi Kako, Yoshinobu Kanda
    ANNALS OF HEMATOLOGY 95 (9) 1513 - 1519 0939-5555 2016/09 [Refereed][Not invited]
     
    The BEAM regimen consisting of carmustine (BCNU), etoposide, cytarabine, and melphalan (MEL) is widely used before autologous hematopoietic stem cell transplantation (auto-HSCT) for lymphoma. However, intravenous BCNU is not available in Japan, and therefore, ranimustine (MCNU) has been used instead of BCNU (the MEAM regimen). We retrospectively analyzed the outcome of 79 adult patients who underwent auto-HSCT for lymphoma using this regimen in two centers, with 1- and 2-day dosing of MEL, respectively. Three-year overall survival (OS) and progression-free survival (PFS) probabilities were 77.3 and 56.5 % in the entire population and 71.7 and 58.0 % in patients with diffuse large B cell lymphoma. These outcomes were at least equivalent to those with the BEAM regimen. There was no regimen-related pulmonary toxicity. In a multivariate analysis, older age was the only factor that was significantly associated with for OS. In a comparison of the two MEL dosing schedules, while there was no significant differences in either OS or PFS, diarrhea was observed more frequently with 1-day dosing of MEL. In conclusion, the MEAM regimen appeared to be a promising conditioning regimen in auto-HSCT for lymphoma. A large prospective study is warranted to confirm the current findings.
  • Daisuke Minakata, Shin-ichiro Fujiwara, Shoko Ito, Kiyomi Mashima, Kento Umino, Hirofumi Nakano, Yasufumi Kawasaki, Miyuki Sugimoto, Ryoko Yamasaki, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi, Yoshinobu Kanda
    LEUKEMIA RESEARCH 42 82 - 87 0145-2126 2016/03 [Refereed][Not invited]
     
    This retrospective analysis compared the efficacy of intensive induction therapy consisting of daunorubicin and cytarabine (DNR-AraC) to that of less-intensive therapy including low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming (CAG). Patients aged 60 years or older who were newly diagnosed as acute myeloid leukemia (AML) were analyzed. Sixty-four and 48 patients were treated with DNR-AraC and CAG, respectively. The complete remission rates, 3-year overall survival and event-free survival in the DNR-AraC group were significantly superior to those in the CAG group (65.6% vs. 29.2%, p < 0.001, 38.4% vs. 12.3%, p = 0.0033, and 20.3% vs. 7.8%, p = 0.0030, respectively), although these differences were not statistically significant in multivariate analyses. Next, we calculated a propensity score for selecting the CAG regimen from six factors. The DNR-AraC regimen was associated with better survival than the CAG regimen in a low propensity score group, but there was no difference in survival between regimens in a high propensity score group. Intensive therapy should be performed for patients with sufficient general and comorbid conditions, but less-intensive therapy may be sufficient for patients with higher age, myelodysplasia-related changes, and lower white blood cell counts, which were relevant factors in the propensity score calculation. (C) 2015 Elsevier Ltd. All rights reserved.
  • Kaoru Hatano, Tadashi Nagai, Tomohiro Matsuyama, Yu Sakaguchi, Shin-ichiro Fujiwara, Iekuni Oh, Kazuo Muroi, Keiya Ozawa
    ACTA HAEMATOLOGICA 133 (1) 98 - 100 0001-5792 2015 [Refereed][Not invited]
  • Takahiro Suzuki, Iekuni Oh, Ken Ohmine, Akiko Meguro, Masaki Mori, Shin-ichiro Fujiwara, Chihiro Yamamoto, Tadashi Nagai, Keiya Ozawa
    INTERNATIONAL JOURNAL OF HEMATOLOGY 101 (1) 32 - 36 0925-5710 2015/01 [Refereed][Not invited]
     
    Erythropoiesis-stimulating agents (ESAs) are used to ameliorate anemia in lower-risk myelodysplastic syndromes (MDS). Serum erythropoietin (EPO) level < 500 IU/L is widely accepted as a major predictive factor for response to ESAs. However, few data about EPO levels in the Japanese population are available. We therefore evaluated distribution of serum EPO levels in Japanese patients with MDS. Forty-three cases were analyzed; 30 were classified as lower-risk MDS (low or intermediate-1 by the international prognostic scoring system). Twenty-two cases were transfusion dependent. The overall median hemoglobin level was 7.7 g/dL. The median value of serum EPO was 254 IU/L (range: 16.4-23,000). Serum EPO levels had a strong inverse correlation with hemoglobin levels, and a significantly larger proportion of patients showed high EPO levels (> 500 IU/L) in the transfusion-dependent group. In the higher-risk group, no significant correlation between EPO and hemoglobin was observed. Regression analyses showed that serum EPO of 500 IU/L corresponds to 8.29 g/dL of hemoglobin in lower-risk MDS. The results indicate that patients with hemoglobin levels of 8.0 g/dL or more, who are still transfusion independent, may be good candidates for ESA treatment.
  • Shin-ichiro Fujiwara, Kazuo Muroi, Raine Tatara, Tomohiro Matsuyama, Ken Ohmine, Takahiro Suzuki, Masaki Mori, Tadashi Nagai, Akira Tanaka, Keiya Ozawa
    LEUKEMIA & LYMPHOMA 55 (2) 307 - 313 1042-8194 2014/02 [Refereed][Not invited]
     
    CD25 expression in follicular lymphoma (FL) has not yet been investigated. Eighty-five patients with newly diagnosed FL were retrospectively evaluated. On two-color flow cytometric analysis, CD25 was detected on CD19 + and CD20 + lymphoma cells. CD25 expression in FL tended to be higher than in reactive lymphadenopathy, but was lower than in diffuse large B-cell lymphoma. Patients with CD25 + FL (n = 12) showed clinical features of elevated soluble interleukin-2 receptor (IL-2R) levels, B symptoms and an advanced age compared with CD25 - FL (n = 73). The overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients with CD25 + FL were significantly inferior to those with CD25 - FL (ORR, 60 vs. 93%; 2-year PFS, 32 vs. 80.3%; 6-year OS, 47.4 vs. 85.9%, respectively). Multivariate analysis demonstrated that CD25 positivity is an independent prognostic factor for PFS and OS in FL. CD25 + FL may constitute a distinct subgroup associated with aggressiveness and an inferior prognosis.
  • Raine Tatara, Makoto Sato, Shin-ichiro Fujiwara, Iekuni Oh, Kazuo Muroi, Keiya Ozawa, Tadashi Nagai
    INTERNAL MEDICINE 53 (20) 2365 - 2368 0918-2918 2014 [Refereed][Not invited]
     
    Hemophagocytic lymphohistiocytosis (HLH), which is associated with various underlying conditions, is characterized by hypercytokinemia. Because it is frequently lethal, immediate mitigation of the hypercytokinemia is vital to save patients, particularly when treatments for the patient's underlying condition are ineffective on HLH. We herein present a case of Hodgkin lymphoma associated with HLH in which the HLH did not improve even after chemotherapy. We attempted to save the patient using hemoperfusion with a polymyxin B-immobilized fiber column to remove cytokines; following this treatment, the patient rapidly recovered. Hemoperfusion may be a strategic method to rescue intractable HLH patients.
  • Muroi K, Fujiwara S, Tatara R, Sato K, Oh I, Ohmine K, Suzuki T, Nagai T, Ozawa K, Kanda Y
    Journal of clinical and experimental hematopathology : JCEH 54 (3) 243 - 245 1346-4280 2014 [Refereed][Not invited]
  • Fujiwara S, Muroi K, Tatara R, Ohmine K, Matsuyama T, Mori M, Nagai T, Ozawa K
    Case reports in hematology 2014 272458  2090-6560 2014 [Refereed][Not invited]
  • Kazutaka Fukumura, Yoshihiro Yamashita, Masahito Kawazu, Eirin Sai, Shin-Ichiro Fujiwara, Naoya Nakamura, Kengo Takeuchi, Mizuo Ando, Kohei Miyazono, Toshihide Ueno, Keiya Ozawa, Hiroyuki Mano
    Oncology Reports 30 (4) 1542 - 1548 1021-335X 2013/10 [Refereed][Not invited]
     
    Peripheral T-cell lymphoma (PTCL) is an aggressive lymphoma with a 5-year overall survival rate of < 30%. To identify carcinogenesis-related genes in PTCL, we conducted high-throughput resequencing of target-captured cDNA in a PTCL specimen, revealing a total of 19 missense mutations among 18 independent genes. One of such substitutions, c.2201G> A in STK10 cDNA, replaces an arginine residue to a histidine (R634H) in the encoded protein. Of note, while wild-type STK10 suppresses NF-κ B activity and potentiates dexamethasone-induced apoptosis, the R634H change significantly decreases such pro-apoptotic activity. This c.2201G> A change of STK10 was also identified in another PTCL specimen, but now registered as a single nucleotide polymorphism in the latest dbSNP database. Furthermore, other somatic mutations of STK10 have been reported, and we now reveal that some of them (L85P and K277E) have more profound anti-apoptotic effects compared to R634H. These results suggest that STK10 functions as a tumor suppressor gene, and that dysfunction of STK10 activity either through polymorphism or somatic mutations may confer anti-apoptotic effects contributing to carcinogenesis.
  • Shin-ichiro Fujiwara, Kazuo Muroi, Yuji Hirata, Kazuya Sato, Tomohiro Matsuyama, Ken Ohmine, Takahiro Suzuki, Katsutoshi Ozaki, Masaki Mori, Tadashi Nagai, Akira Tanaka, Keiya Ozawa
    HEMATOLOGY 18 (1) 14 - 19 1024-5332 2013/01 [Refereed][Not invited]
     
    CD25 (interluekin-2 receptor) expression in diffuse large B-cell lymphoma (DLBCL) cells has been not examined. To characterize CD25(+) DLBCL, 123 patients, who were newly diagnosed with DLBCL, were analyzed by single-color flow cytometry (FCM). CD25-positivity was significantly higher in DLBCL patients (n = 123; mean +/- SD, 27.8 +/- 30.6%) than in those with reactive lymphadenopathy (n = 16; mean +/- SD, 8.6 +/- 4.3%) and follicular lymphoma (n = 60; mean +/- SD, 12.7 +/- 12.4%). By two-color FCM, CD25/CD19 or CD25/CD20 dual positivity in DLBCL patients was shown: mean +/- SD, 63.7 +/- 25.5% (n = 13) and 55.0 +/- 28.1% (n = 14), respectively. Eighty-two percent of the patients with DLBCL received rituximab combined with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. A cut-off value of 60% with CD25-positivity clearly divided patients with DLBCL into two groups: CD25-high or CD25-low DLBCL. Although clinical and immunophenotypic features were not significantly different in both groups, the former showed a significantly poorer response and more inferior progression-free survival than the latter. CD25 may be a new prognostic marker and could be a therapeutic target in DLBCL.
  • Raine Tatara, Tadashi Nagai, Mizuho Suzuki, Iekuni Oh, Shin-ichiro Fujiwara, Masataro Norizuki, Kazuo Muroi, Keiya Ozawa
    INTERNAL MEDICINE 52 (17) 1987 - 1990 0918-2918 2013 [Refereed][Not invited]
     
    We herein report the findings of a case of myelodysplastic syndrome that was complicated by septicemia and meningoencephalitis, both of which were caused by Bacillus cereus. In contrast to all of the previous cases of B. cereus that have been seen at our institution, this patient did not have any invasive devices, such as a central venous catheter, that could have acted as a conduit for a B. cereus infection. Although B. cereus-induced meningoencephalitis is often lethal, the immediate treatment with a regimen of antibiotics including vancomycin was effective in eradicating the infection and, therefore, in reversing both the septicemia and the meningoencephalitis.
  • Muroi K, Fujiwara S, Tatara R, Sugimoto M, Yamamoto C, Uehara E, Meguro A, Hatano K, Okazuka K, Oh I, Ohmine K, Suzuki T, Mori M, Nagai T, Ozawa K
    Journal of clinical and experimental hematopathology : JCEH 3 53 247 - 250 1346-4280 2013 [Refereed][Not invited]
  • Hosonuma R, Fujiwara S, Sasazaki M, Hirata Y, Yamamoto C, Uesawa M, Oh I, Matsuyama T, Mori M, Ozawa K, Muroi K
    [Rinsho ketsueki] The Japanese journal of clinical hematology 4 53 469 - 471 0485-1439 2012/04 [Refereed][Not invited]
  • Oka S, Muroi K, Fujiwara S, Oh I, Matsuyama T, Ohmine K, Suzuki T, Ozaki K, Mori M, Nagai T, Ozawa K, Hanafusa T
    Journal of clinical and experimental hematopathology : JCEH 1 52 63 - 66 1346-4280 2012 [Refereed][Not invited]
  • Kobayashi H, Matsuyama T, Oka S, Fujiwara S, Oh I, Suzuki T, Ozaki K, Mori M, Nagai T, Ozawa K, Muroi K
    Journal of clinical and experimental hematopathology : JCEH 1 52 81 - 83 1346-4280 2012 [Refereed][Not invited]
  • Oka S, Muroi K, Sato K, Fujiwara S, Oh I, Matsuyama T, Ohmine K, Suzuki T, Ozaki K, Mori M, Nagai T, Fukushima N, Fukushima N, Tanaka A, Ozawa K
    Journal of clinical and experimental hematopathology : JCEH 2 52 127 - 131 1346-4280 2012 [Refereed][Not invited]
  • Akiko Meguro, Katsutoshi Ozaki, Kazuya Sato, Iekuni Oh, Shinichiro Fujiwara, Rie Hosonuma, Miyuki Sasazaki, Yuji Kikuchi, Yuji Hirata, Chihiro Yamamoto, Mitsuyo Uesawa, Hiroyuki Kobayashi, Haruko Matsu, Hiroshi Okabe, Eisuke Uehara, Akinori Nishikawa, Raine Tatara, Kaoru Hatano, Chizuru Yamamoto, Tomohiro Matsuyama, Masaki Toshima, Masuzu Ueda, Ken Ohmine, Takahiro Suzuki, Masaki Mori, Tadashi Nagai, Kazuo Muroi, Keiya Ozawa
    LEUKEMIA & LYMPHOMA 53 (1) 43 - 49 1042-8194 2012/01 [Refereed][Not invited]
     
    In the rituximab era, several large studies have suggested that full-dose rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) might be the best treatment for patients with diffuse large B-cell lymphoma (DLBCL) aged 60 years and older. However, it remains unclear whether this is also the case for those aged 70 years and older. Previously untreated patients with DLBCL aged 70 years and older (elderly) were treated with R-70%CHOP, and patients younger than 70 years (younger) were treated with full-dose R-CHOP every 3 weeks, for a total of 6-8 cycles. Complete remission (CR) rates in elderly versus younger patients were 75 vs. 78% (p = 0.7), respectively. The 3-year overall survival, event-free survival and progression-free survival of elderly versus younger patients were 58 vs. 78% (p < 0.05), 45 vs. 70% (p < 0.05) and 64 vs. 72% (p = 0.43), respectively. Severe adverse events were more frequent in the elderly, even with the dose reduction in that age group. Three-year PFS with R-70% CHOP for patients aged 70 years and older was not significantly worse than that with full-dose R-CHOP for younger patients, suggesting that R-70% CHOP might be a reasonable choice for patients with DLBCL aged 70 years and older, especially for those with comorbidities.
  • Yuji Hirata, Koji Kishino, Fumiko Onozaki, Yoko Nakaki, Shin-ichiro Fujiwara, Chizuru Yamamoto, Kazuya Sato, Tomohiro Matsuyama, Katsutoshi Ozaki, Masaki Mori, Keiya Ozawa, Kazuo Muroi
    HEMATOLOGY 16 (4) 221 - 224 1024-5332 2011/07 [Refereed][Not invited]
     
    Transplantation with cryopreserved allogeneic peripheral blood stem cells (PBSCs) from related donors is widely conducted in Japan. To freeze PBSCs, a solution containing dimethyl sulfoxide (DMSO), which can have various adverse effects, is added. DMSO-depleted allogeneic PBSCs were transplanted into 21 patients. The cryoprotectant was manually removed from thawed PBSCs and the cells were mixed with a solution containing citrate dextrose as an anticoagulant and RPMI-1640 medium. DMSO-depleted PBSCs were immediately infused into patients subjected to conditioning. Infusion-related adverse effects were only observed in three patients. The median neutrophil recovery (>= 0.5 x 10(9)/l) and platelet recovery (>= 20 x 10(9)/l) were 13.0 and 14.0 days, respectively. Only one patient with mixed-lineage leukemia in non-complete remission did not show engraftment, likely due to a second transplantation and a two-antigen disparity in human leukocyte antigen system A. The results suggest the removal of DMSO from thawed PBSCs to be safe and useful for transplantation.
  • Kazuya Sato, Katsutoshi Ozaki, Shin-ichiro Fujiwara, Iekuni Oh, Tomohiro Matsuyama, Ken Ohmine, Takahiro Suzuki, Masaki Mori, Tadashi Nagai, Kazuo Muroi, Keiya Ozawa
    INTERNATIONAL JOURNAL OF HEMATOLOGY 92 (4) 647 - 650 0925-5710 2010/11 [Refereed][Not invited]
     
    According to the international working group response criteria for malignant lymphoma revised in 2007, 18F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) combined with or without computed tomography (CT) is recommended for pre-treatment staging and response assessment among patients with diffuse large B-cell lymphoma and Hodgkin lymphoma. Recently, along with the widespread use of PET/CT, unexpected uptake and accumulation of (18)FDG has been reported. Discussed in the present report are patients with malignant lymphoma and second primary carcinomas that were incidentally found by PET/CT. A total of 497 consecutive PET/CT were performed on 290 patients with malignant lymphoma in our institution from April 2008 through March 2010. Eight patients (2.8%) had pathologically confirmed second primary carcinomas consisting of 4 colon cancers, 3 lung cancers, and 1 pancreatic cancer. Two cases were diagnosed at the initial staging, and the others were detected after treatment for lymphoma. It is noteworthy that PET revealed high accumulations of (18)FDG in 5 (62.5%) of the 8 patients without corresponding tumors in conventional CT. All of the 4 patients with colon carcinoma underwent curative surgery. The present study suggests that incidental findings by PET in malignant lymphoma can lead to early detection and successful treatment of second malignancies.
  • Tadashi Nagai, Ken Ohmine, Shin-ichiro Fujiwara, Mitsuyo Uesawa, Chihiro Sakurai, Keiya Ozawa
    LEUKEMIA RESEARCH 34 (8) 1057 - 1063 0145-2126 2010/08 [Refereed][Not invited]
     
    Small molecules are attractive agents for the treatment of leukemia. We found that a combination of a farnesyltransferase inhibitor, tipifarnib, and an mTOR inhibitor, rapamycin, synergistically inhibited the growth of myeloid leukemia cell lines and primary leukemia cells by inducing apoptosis and cell-cycle blockage. The combined agents reduced the level of phospho-ERK1/2, suggesting that they altered the network of signaling pathways. They also showed synergistic effects in tipifarnib-resistant K562/RR cells. The results support the utility of this combination as a potential therapy for leukemia. The combination might also be effective in overcoming resistance to tipifarnib. (C) 2010 Elsevier Ltd. All rights reserved.
  • Tomoaki Wada, Yoshihiro Yamashita, Yasushi Saga, Kayoko Takahashi, Koji Koinuma, Young Lim Choi, Ruri Kaneda, Shin-Ichiro Fujiwara, Manabu Soda, Hideki Watanabe, Kentaro Kurashina, Hisashi Hatanaka, Munehiro Enomato, Shuji Takada, Hiroyuki Mano, Mitsuaki Suzuki
    INTERNATIONAL JOURNAL OF ONCOLOGY 35 (5) 973 - 976 1019-6439 2009/11 [Refereed][Not invited]
     
    The purpose of this study was to screen for genes involved in ovarian carcinogenesis in an attempt to develop an effective molecular-targeted therapy for ovarian cancer. We constructed retroviral expression libraries for the human ovarian cancer cell lines SHIN-3 and TYK-CPr, and performed a focus formation assay with 3T3 cells. As a result, proteasome subunit beta-type 2 (PSMB2), ubiquitin-specific protease 14 (USP14), and keratin 8 (KRT8) were identified from SHIN-3, and polymerase H RNA subunit (POLR2E), chaperonin containing T-complex polypeptide 1 subunit 4 (CCT4), glia maturation factor beta (GMFB), and neuroblastoma ras viral oncogene homolog (NRAS) from TYK-CPr. NRAS gene analysis revealed a CAA -> AAA substitution at codon 61, resulting in a Glu -> Lys change at position 61. When the mutant NRAS was introduced into fibroblasts for its expression, many transformed foci were generated, confirming the transforming ability of the mutant NRAS.
  • Satoko Oka, Kazuo Muroi, Masaki Mori, Tomohiro Matsuyama, Shin-Ichiro Fujiwara, Iekuni Oh, Kazuya Sato, Satoru Kikuchi, Masuzu Ueda, Masaki Toshima, Takahiro Suzuki, Katsutoshi Ozaki, Tadashi Nagai, Keiya Ozawa
    LEUKEMIA & LYMPHOMA 50 (2) 290 - 293 1042-8194 2009 [Refereed][Not invited]
  • Manabu Soda, Young Lim Choi, Munehiro Enomoto, Shuji Takada, Yoshihiro Yamashita, Shunpei Ishikawa, Shin-ichiro Fujiwara, Hideki Watanabe, Kentaro Kurashina, Hisashi Hatanaka, Masashi Bando, Shoji Ohno, Yuichi Ishikawa, Hiroyuki Aburatani, Toshiro Niki, Yasunori Sohara, Yukihiko Sugiyama, Hiroyuki Mano
    NATURE 448 (7153) 561 - U3 0028-0836 2007/08 [Refereed][Not invited]
     
    Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells. Mouse 3T3 fibroblasts forced to express this human fusion tyrosine kinase generated transformed foci in culture and subcutaneous tumours in nude mice. The EML4-ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined; these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. Our data demonstrate that a subset of NSCLC patients may express a transforming fusion kinase that is a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC.
  • Mori M, Muroi K, Matsuyama T, Oka S, Ono Y, Yamamoto C, Uesawa M, Okabe H, Matsu H, Tatara R, Kikuchi Y, Fujiwara S, Kikuchi S, Sato K, Ueda M, Toshima M, Ozaki K, Takatoku M, Nagai T, Ozawa K
    [Rinsho ketsueki] The Japanese journal of clinical hematology 8 48 624 - 631 0485-1439 2007/08 [Refereed][Not invited]
  • Hisashi Hatanaka, Shuji Takada, Young Lim Choi, Shin-ichiro Fujiwara, Manabu Soda, Munehiro Enomoto, Kentaro Kurashina, Hideki Watanabe, Yoshihiro Yamashita, Kentaro Sugano, Hiroyuki Mano
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 356 (3) 723 - 726 0006-291X 2007/05 [Refereed][Not invited]
     
    Colorectal cancer (CRC) is one of the leading causes of cancer death in humans. In order to identify novel cancer-promoting genes in CRC, we here constructed a retroviral cDNA expression library from a CRC cell line RKO, and used it for a focus formation assay with mouse 3T3 fibroblasts, leading to the identification of 42 independent cDNAs. One of such cDNAs turned out to encode purinergic receptor P2Y, G-protein coupled, 2 (P2RY2). The oncogenic potential of P2RY2 was confirmed in vitro with the focus formation assay as well as soft agar-growth assay, and also in vivo with a tumorigenicity assay in nude mice. While our P2RY2 cDNA encodes a protein with two amino-acid substitutions compared to the reported one, we have confirmed that the wild-type P2RY2 has a strong transforming potential as well. These results indicate an unexpected role of P2RY2 in the carcinogenesis of human cancers. (c) 2007 Elsevier Inc. All rights reserved.
  • Young Lim Choi, Ruri Kaneda, Tomoaki Wada, Shin-ichiro Fujiwara, Manabu Soda, Hideki Watanabe, Kentaro Kurashina, Hisashi Hatanaka, Munehiro Enomoto, Shuji Takada, Yoshihiro Yamashita, Hiroyuki Mano
    LEUKEMIA RESEARCH 31 (2) 203 - 209 0145-2126 2007/02 [Refereed][Not invited]
     
    To identify transforming genes in acute myeloid leukemia (AML) we here constructed a retroviral cDNA expression library from an AML patient, and then used this library to infect a mouse cell line 32Dcl3-mCAT. cDNA inserts of the cell clones which proliferated in the presence of granulocyte colony-stimulating factor were derived from JAK3 encoding a JAK3 mutant with a valine-to-alanine substitution at codon 674 and two additional amino acid substitutions. The transforming activity of JAK3(V674A) was confirmed by its introduction into 32Dcl3-mCAT. Sequencing of the original JAK3 cDNA derived from the patient, however, failed to detect the V674A mutation. (c) 2006 Elsevier Ltd. All rights reserved.
  • Shin-Ichiro Fujiwara, Kazuo Muroi, Satoru Kikuchi, Chizuru Kawano-Yamamoto, Tomohiro Matsuyama, Masaki Mori, Tadashi Nagai, Miyuki Akutsu, Keiya Ozawa
    LEUKEMIA & LYMPHOMA 48 (3) 640 - 642 1042-8194 2007 [Refereed][Not invited]
  • Shin-Ichiro Fujiwara, Yoshihiro Yamashita, Young Lim Choi, Hideki Watanabe, Kentaro Kurashina, Manabu Soda, Munehiro Enomoto, Hisashi Hatanaka, Shuji Takada, Keiya Ozawa, Hiroyuki Mano
    LEUKEMIA & LYMPHOMA 48 (5) 978 - 986 1042-8194 2007 [Refereed][Not invited]
     
    Biphenotypic acute leukemia ( BAL) is a relatively rare subtype of acute leukemia characterized by the presence of both myeloid and lymphoid cell surface antigens. We have now screened for transforming genes in BAL blasts with the use of the focus formation assay with a retroviral cDNA expression library constructed from malignant blasts isolated from a BAL patient. Some of the retroviral inserts recovered from transformed foci were found to encode wild-type purinergic receptor P2Y, G protein coupled, 8 ( P2RY8). The oncogenic potential of P2RY8 was confirmed with the in vitro focus formation assay as well as with an in vivo tumorigenicity assay in nude mice. A variety of luciferase-based reporter assays revealed that P2RY8 increased both the trans-activation activities of CREB and Elk-1 as well as the transcriptional activities of the serum response element and enhancer-promoter fragments of the c-Fos and c-Myc genes. Quantitation of P2RY8 mRNA in CD34(+) cells of bone marrow showed that P2RY8 expression is frequently increased in leukemia patients, especially in those with refractory disease. Our data thus reveal an abundant expression of P2RY8 in leukemic cells and its unexpected role in the pathogenesis of acute leukemia.
  • Shuji Takada, Eugene Berezikov, Yoshihiro Yamashita, Mariana Lagos-Quintana, Wigard P. Kloosterman, Munehiro Enomoto, Hisashi Hatanaka, Shin-ichiro Fujiwara, Hideki Watanabe, Manabu Soda, Young Lim Choi, Ronald H. A. Plasterk, Edwin Cuppen, Hiroyuki Mano
    NUCLEIC ACIDS RESEARCH 34 (17) e115  0305-1048 2006/10 [Refereed][Not invited]
     
    MicroRNAs (miRNAs) are noncoding RNA molecules of 21 to 24 nt that regulate the expression of target genes in a post-transcriptional manner. Although evidence indicates that miRNAs play essential roles in embryogenesis, cell differentiation and pathogenesis of human diseases, extensive miRNA profiling in cells or tissues has been hampered by the lack of sensitive cloning methods. Here we describe a highly efficient profiling method, termed miRNA amplification profiling (mRAP), as well as its application both to mouse embryos at various developmental stages and to adult mouse organs. A total of 77 436 Small-RNA species was sequenced, with 11 776 of these sequences found to match previously described miRNAs. With the use of a newly developed computational prediction algorithm, we further identified 229 independent candidates for previously unknown miRNAs. The expression of some of these candidate miRNAs was confirmed by northern blot analysis and whole-mount in situ hybridization. Our data thus indicate that the total number of miRNAs in vertebrates is larger than previously appreciated and that the expression of these molecules is tightly controlled in a tissue- and developmental stage-specific manner.
  • Takahiro Nagashima, Kazuo Muroi, Chizuru Kawano-Yamamoto, Takuji Miyoshi, Raine Tatara, Akiko Meguro, Shin-Ichiro Fujiwara, Yoko Obara, Iekuni Oh, Satoru Kikuchi, Kazuya Sato, Tomohiro Matsuyama, Masaki Toshima, Ken Ohmine, Katsutoshi Ozaki, Masaaki Takatoku, Masaki Mori, Tadashi Nagai, Keiya Ozawa
    LEUKEMIA & LYMPHOMA 47 (8) 1613 - 1617 1042-8194 2006/08 [Refereed][Not invited]
     
    Frequency and clinical significance of cerebrospinal fluid (CSF) pleocytosis in hemopoietic stem cell (HSC) transplantation were surveyed. Cyclosporine (CSA)- or tacrolimus (FK506)-based regimens were used as graft-vs-host disease (GVHD) prophylaxis in allogeneic HSC transplantation. CSF pleocytosis with or without neurologic symptoms was detected in 12 of 25 patients receiving allogeneic HSC transplants but in none of 11 patients receiving autologous HSC transplants. Of the 12 patients with CSF pleocytosis, only one patient developed leukoencephalopathy later. There was a correlation between CSF cell numbers and trough levels of CSA but not with those of FK506. In patients receiving allogeneic HSC transplants, CSF pleocytosis may be relatively common and may reflect neurologic damage associated with calcineurin inhibitors.
  • S Takada, J Ota, N Kansaku, H Yamashita, T Izumi, M Ishikawa, T Wada, R Kaneda, YL Choi, K Koinuma, SI Fujiwara, H Aoki, H Kisanuki, Y Yamashita, H Mano
    GENERAL AND COMPARATIVE ENDOCRINOLOGY 145 (2) 208 - 213 0016-6480 2006/01 [Refereed][Not invited]
     
    Sox9 is a member of the Sry-type HMG-box (Sox) gene family. It encodes a transcription factor and is thought to be important for sexual differentiation in chicken. In the present study we have isolated Sox9 cDNAs from quail and duck, and examined the expression patterns of the corresponding genes in early embryonic gonads by whole-mount in situ hybridization. We developed a polymerase chain reaction-based protocol to identify the sex of quail and duck embryos before its morphological manifestation. Sox9 expression was first detected on days 5 and 7 in the gonads of male quail and duck embryos, respectively, and was not apparent in female gonads at these stages. These expression patterns are similar to that of chicken Sox9. Our results thus suggest that the expression of quail and duck Sox9 is associated with testis differentiation. (c) 2005 Elsevier Inc. All rights reserved.
  • S Fujiwara, Y Yamashita, YM Choi, T Wada, R Kaneda, S Takada, Y Maruyama, K Ozawa, H Mano
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 338 (2) 1256 - 1262 0006-291X 2005/12 [Refereed][Not invited]
     
    Pancreatic ductal carcinoma (PDC) remains one of the most intractable human malignancies. To obtain insight into the molecular pathogenesis of PDC we constructed a retroviral cDNA expression library with total RNA isolated from the PDC cell line MiaPaCa-2. Screening of this library with the use of a focus formation assay with NIH 3T3 mouse fibroblasts resulted in the identification of 13 independent genes with transforming activity. One of the cDNAs thus identified encodes an NH2-terminally truncated form of the lymphotoxin-beta receptor (LTBR). The transforming activity of this short-type LTBR in 3T3 cells was confirmed by both an in vitro assay of cell growth in soft agar and an in vivo assay of turnorigenicity in nude mice. The full-length (wild-type) LTBR protein was also found to manifest similar transforming activity. These observations suggest that LTBR, which belongs to the tumor necrosis factor receptor superfamily of proteins, may contribute to human carcinogenesis. (c) 2005 Elsevier Inc. All rights reserved.
  • H Kisanuki, YL Choi, T Wada, R Moriuchi, S Fujiwara, R Kaneda, K Koinuma, M Ishikawa, S Takada, Y Yamashita, H Mano
    EUROPEAN JOURNAL OF CANCER 41 (14) 2170 - 2175 0959-8049 2005/09 [Refereed][Not invited]
     
    Pancreatic ductal carcinoma (PDC) remains one of the most intractable malignancies in humans. In order to clarify the molecular events underlying the carcinogenesis in PDC, we constructed a retroviral cDNA expression library from a PDC cell line, and used it to screen transforming genes in PDC by a focus formation assay with mouse 3T3 fibroblasts. We could obtain a total of 30 transformed cell foci in the screening, and one of the cDNA inserts harvested from such cell clones turned out to encode a wild-type human ARAF1. Unexpectedly, a long terminal repeat-driven overexpression of ARAF1 mRNA was confirmed to induce transformed foci in fibroblasts. The oncogenic potential of ARAF1 was examined by injecting the transformed fibroblasts into athymic nude mice. Importantly, ARAF1 mRNA was highly expressed in pancreatic ductal cell specimens purified from patients with PDC. These results have unveiled the transforming potential of ARAF1 protein, and also suggest that quantity of intracellular ARAF1 may be important in carcinogenesis of various human cancers. (c) 2005 Elsevier Ltd. All rights reserved.
  • C Tsutsumi, M Ueda, Y Miyazaki, Y Yamashita, YL Choi, J Ota, R Kaneda, K Koinuma, S Fujiwara, H Kisanuki, M Ishikawa, K Ozawa, M Tomonaga, H Mano
    EXPERIMENTAL HEMATOLOGY 32 (9) 828 - 835 0301-472X 2004/09 [Refereed][Not invited]
     
    Objective. Acute myeloid leukemia (AML) develops de novo or secondarily to either myelodysplastic syndrome (MDS) or anticancer treatment (therapy-related leukemia, TRL). Prominent dysplasia of blood cells is apparent in individuals with MDS-related AML as well as in some patients with TRL or even with de novo AML. The clinical entity of AML with multilineage dysplasia (AML-MLD) is likely to be an amalgamation of MDS-related AML and de novo AML-MLD. The aim of this study was to clarify, by the use of high-density oligonucleotide microarrays, whether these subcategories of AML are intrinsically distinct from each other. Materials and Methods. The AC133(+) hematopoietic stem cell-like fractions were purified from the bone marrow of individuals with de novo AML without dysplasia (n = 15), AML-MLD (n = 11), MDS-related AML (n = 11), or TRL (n = 2), and were subjected to the synthesis of cRNA which was subsequently hybridized to microarray harboring oligonucleotide corresponding to more than 12,000 probe sets. Results. We could identify many genes whose expression was specific to these various subcategories of AML. Furthermore, with the correspondence analysis/three-dimensional projection strategy, we were able to visualize the independent, yet partially overlapping, nature of current AML subcategories on the basis of their transcriptomes. Conclusion. Our data indicate the possibility of subclassification of AML based on gene expression profiles of leukemic blasts. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.
  • J Ota, Y Yamashita, K Okawa, H Kisanuki, S Fujiwara, M Ishikawa, YL Choi, S Ueno, R Ohki, K Koinuma, T Wada, D Compton, T Kadoya, H Mano
    ONCOGENE 22 (36) 5720 - 5728 0950-9232 2003/08 [Refereed][Not invited]
     
    DNA microarray analysis has been applied to identify molecular markers of human hematological malignancies. However, the relatively low correlation between the abundance of a given mRNA and that of the encoded protein makes it important to characterize the protein profile directly, or 'proteome,' of malignant cells in addition to the 'transcriptome.' To identify proteins specifically expressed in leukemias, here we isolated AC133(+) hematopoietic stem cell-like fractions from the bone marrow of 13 individuals with various leukemic disorders, and compared their protein profiles by two-dimensional electrophoresis. A total of 11 differentially expressed protein spots corresponding to 10 independent proteins were detected, and peptide fingerprinting combined with mass spectrometry of these proteins revealed them to include NuMA (nuclear protein that associates with the mitotic apparatus), heat shock proteins, and redox regulators. The abundance of NuMA in the leukemic blasts was significantly related to the presence of complex karyotype anomalies. Conditional expression of NuMA in a mouse myeloid cell line resulted in the induction of aneuploidy, cell cycle arrest in G(2)-M phases, and apoptosis. These results demonstrate the potential of proteome analysis with background-matched cell fractions obtained from fresh clinical specimens to provide insight into the mechanism of human leukemogenesis.

MISC

  • KISHINO Koji, NAKAKI Yoko, ONOZAKI Fumiko, SHINDOU Seiko, OTSUKI Ikuko, KOBAYASHI Mika, OBATA Takashi, TAMURA Mistuko, SUGANO Naoko, FUJIWARA Shin-ichiro, MATSUYAMA Tomohiro, MORI Masaki, OZAWA Keiya, MUROI Kazuo  日本輸血細胞治療学会誌 = Japanese journal of transfusion and cell therapy  58-  (3)  456  -462  2012/06  [Not refereed][Not invited]
  • HOSONUMA Rie, FUJIWARA Shin-ichiro, SASAZAKI Miyuki, HIRATA Yuji, YAMAMOTO Chihiro, UESAWA Mitsuyo, OH Iekuni, MATSUYAMA Tomohiro, MORI Masaki, OZAWA Keiya, MUROI Kazuo  臨床血液  53-  (4)  469  -471  2012/04  [Not refereed][Not invited]
  • Kazuya Sato, Kazuo Muroi, Satoko Oka, Miyuki Sasazaki, Rie Hosonuma, Katsutoshi Ozaki, Shin-ichiro Fujiwara, Iekuni Oh, Tomohiro Matsuyama, Ken Ohmine, Takahiro Suzuki, Masaki Mori, Tadashi Nagai, Keiya Ozawa  Jichi Medical University journal  34-  149  -157  2012/03  [Not refereed][Not invited]
     
    Mesenchymal stromal cells (MSCs) have been reported to have immunomodulatory effects and ameliorate severe graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). We have conducted a pilot study using human MSCs for the treatment of steroid-resistant GVHD. Between January 2006 and December 2010, 10 patients (7 males and 3 females) with a median age of 37.9 years (range: 23-65 years) who had steroid-resistant GVHD were enrolled in this study. MSCs were isolated from bone marrow of the patient's relatives. Among these 10 patients, three were treated with MSCs. The other seven did not receive MSC treatment because of an improvement in GVHD due to the addition of immunosuppressants including methylprednisolone, spontaneous GVHD regression, or early death. Of the three patients treated with MSCs, one showed an improvement in his intestinal GVHD, another showed no change in his intestinal GVHD and third had his dose of prednisolone successfully decreased without progression of his intestinal GVHD. No immediate adverse reactions associated with MSC infusions were observed. Since the present study was limited to a small number of patients, it is difficult to evaluate the efficacy of MSCs for steroid-resistant GVHD. Further investigations are needed to establish the clinical application of MSCs for steroid-resistant GVHD.
  • FUJIWARA Shin-ichiro, SATO Kazuya, HIRATA Yuji, YAMAMOTO Chizuru, MATSUYAMA Tomohiro, OZAKI Katsutoshi, MORI Masaki, YAGINUMA Kaori, SUGANO Naoko, NAKAKI Yoko, KISHINO Koji, OZAWA Keiya, MUROI Kazuo  日本輸血細胞治療学会誌 = Japanese journal of transfusion and cell therapy  57-  (4)  283  -288  2011/08  [Not refereed][Not invited]
  • Miyuki Sasazaki, Masaki Mori, Mituyo Uesawa, Shinitirou Fuziwara, Yuuzi Kikuti, Kazuya Satou, Tomohiro Matuyama, Ken Oomine, Masuzu Ueda, Takahiro Suzuki, Katutosi Ozaki, Tadashi Nagai, Kazuo Muroi, Keiya Ozawa  Jichi Medical University journal  33-  23  -28  2011/03  [Not refereed][Not invited]
     
    Burkitt lymphoma/leukemia (BL) was formerly recognized as an aggressive malignant lymphoma with a poor prognosis. To confirm whether the prognosis of BL is improved by the Hyper-CVAD/HD-MTX/Ara-C regimen with or without rituximab (group B) compared with the classical treatment regimen for acute lymphoblastic leukemia or non-Hodgkin lymphoma (group A), the outcomes of 10 patients treated in our hospital from 1997 to 2009 were analyzed. The results showed that both groups had achieved complete remission with each induction therapy; however, 5 of 6 patients in group B had long-term remission, while 3 of 4 patients in group A who received bone marrow transplantation relapsed. In conclusion, the new strategy with short-duration combination chemotherapy is safe and useful for BL.
  • Satoko Oka, Kazuo Muroi, Masaki Mori, Tomohiro Matsuyama, Shin-ichiro Fujiwara, Iekuni Oh, Kazuya Sato, Masuzu Ueda, Takahiro Suzuki, Katsutoshi Ozaki, Tadashi Nagai, Keiya Ozawa  Jichi Medical University journal  33-  167  -174  2011/03  [Not refereed][Not invited]
     
    Detection of minimal residual disease (MRD) in acute myeloblastic leukemia (AML) after bone marrow transplantation is important to predict relapse. It is well known that AML cells show various abnormal antigen expressions. MRD was detected in an AML patient after BMT by flow cytometry measurements of CD34+CD15+CD7+ cells. Subsequently, the patient's AML relapsed.
  • OKA Satoko, MATSUYAMA Tomohiro, MORI Masaki, FUJIWARA Shin-ichiro, OHO Iekuni, KIKUCHI Satoru, SATO Kazuya, UEDA Masuzu, TOSHIMA Masaki, SUZUKI Takahiro, OZAKI Katsutoshi, NAGAI Tadashi, OZAWA Keiya, MUROI Kazuo  日本輸血細胞治療学会誌 = Japanese journal of transfusion and cell therapy  55-  (5)  589  -595  2009/11  [Not refereed][Not invited]
  • Tatara Raine, Mori Masaki, Fujiwara Shin-ichiro, Miyoshi Takuji, Sato Kazuya, Yamamoto Chizuru, Matsuyama Tomohiro, Toshima Masaki, Ohmine Ken, Ozaki Katsutoshi, Takatoku Masaaki, Nagai Tadashi, Ozawa Keiya, Muroi Kazuo  Jichi Medical University journal  30-  81  -87  2007/12  [Not refereed][Not invited]
  • MORI Masaki, MUROI Kazuo, MATSUYAMA Tomohiro, OKA Satoko, ONO Yoko, YAMAMOTO Chizuru, UESAWA Mitsuyo, OKABE Hiroshi, MATSU Haruko, TATARA Raine, KIKUCHI Yuji, FUJIWARA Shinichiro, KIKUCHI Satoru, SATO Kazuya, UEDA Masuzu, TOSHIMA Masaki, OZAKI Katsutoshi, TAKATOKU Masaaki, NAGAI Tadashi, OZAWA Keiya  臨床血液 = The Japanese Journal of Clinical Hematology  48-  (8)  624  -631  2007/08  [Not refereed][Not invited]


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