Faculty Profiles - FUJII Nobuharu

Papers - FUJII Nobuharu

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Bronchiolitis obliterans with allogeneic hematopoietic cell transplantation: a 10-year experience of the Okayama BMT Group. Reviewed

Nobuharu Fujii, Koichi Nakase, Shoji Asakura, Keitaro Matsuo, Yuichiro Nawa, Kazutaka Sunami, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Katsuji Shinagawa, Masamichi Hara, Mitsune Tanimoto

International journal of hematology 99 ( 5 ) 644 - 651 2014.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Bronchiolitis obliterans (BO) is a devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). We retrospectively studied 465 patients who underwent HSCT in the Okayama BMT Group between 2000 and 2009, and describe the detailed clinical features of 13 patients with BO. The 5-year cumulative incidence of BO was 3.43 %. The median time from transplantation to onset of BO was 15 months. In seven of the 13 patients, the primary symptom was only cough, indicating that cough was an important initial symptom for early diagnosis. The median duration from the onset of BO to the requirement of O2 supplementation was 13 months and the main cause of death was respiratory failure. History of chronic graft-versus-host disease was a significant risk factor. Furthermore, female recipients were at greater risk of BO than male recipients; however, no other previously reported risk factors were detected. It is currently difficult to prevent BO on the basis of the reported risk factors. A novel strategy for the early diagnosis and treatment of BO is required.

DOI： 10.1007/s12185-014-1556-4

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Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease Reviewed

Sugiyama Haruko, Maeda Yoshinobu, Nishimori Hisakazu, Yamasuji Yoshiko, Matsuoka Ken-ichi, Fujii Nobuharu, Kondo Eisei, Shinagawa Katsuji, Tanaka Takehiro, Takeuchi Kengo, Teshima Takanori, Tanimoto Mitsune

Biology of Blood and Marrow Transplantation 20 ( 2 ) 183 - 191 2014.2

新しい全自動型血液成分分離装置Spectra Optiaを用いた末梢血幹細胞採取-COBE Spectraと比較して- Reviewed

藤井敬子,藤井伸治,淺田騰,西森久和,狩山由貴,池田亮,浅野尚美,小郷博昭,岩月啓氏

日本輸血細胞治療学会誌 59 ( 6 ) 799 - 804 2014.1

Complete resolution of steroid-resistant organizing pneumonia associated with myelodysplastic syndrome following allogeneic hematopoietic cell transplantation. Reviewed International journal

Takeru Asano, Nobuharu Fujii, Daigo Niiya, Hisakazu Nishimori, Keiko Fujii, Ken-Ichi Matsuoka, Koichi Ichimura, Toshihisa Hamada, Eisei Kondo, Yoshinobu Maeda, Yasushi Tanimoto, Katsuji Shinagawa, Mitsune Tanimoto

SpringerPlus 3 3 - 3 2014.1

Language：English Publishing type：Research paper (scientific journal)

Pulmonary complications in patients with hematological malignancies are often caused by infection but are sometimes associated with an underlying disease such as organizing pneumonia (OP). Here, we report a case of life-threatening steroid-resistant OP associated with myelodysplastic syndrome (MDS) and successfully performed allogeneic hematopoietic cell transplantation (HSCT). A 33-year-old female with refractory anemia with excess blasts-1 that had progressed from refractory anemia with ringed sideroblasts and concomitant Sweet's syndrome was admitted. Multiple pulmonary infiltrates were revealed on a chest computed tomography scan, which progressively worsened even after chemotherapy and corticosteroid therapy. No evidence of infection was observed in bronchoalveolar lavage fluid. A histological examination of a transbronchial lung biopsy specimen showed lymphocyte invasion with fibrosis, indicating that the pulmonary infiltrates were OP associated with MDS. Before transplantation, she suffered from respiratory failure and required oxygen supplementation. She developed idiopathic pneumonitis syndrome on day 61 that responded well to corticosteroid therapy, and the OP pulmonary infiltrates improved gradually after HSCT, She was discharged on day 104 and is well without recurrence of OP or MDS 2 years after HSCT.

DOI： 10.1186/2193-1801-3-3

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Pre-transplant risk factors for cryptpgenic organizing pneumonia/brnchiolitis obliterans organizing pneumonia after hematopoietic cell transplantation. Reviewed

Nakasone H, Onizuka M, Suzuki N, Fujii N, Taniguchi S, Kakihana K, Ogawa H, Miyamura K, Eto T, Sakamaki H, Yabe H, Morishima Y, Kato K, Suzuki R, Fukuda T.

Bone Marrow Transplantation 1 - 7 2013.10

Erdheim-Chester病が強く疑われた下垂体機能低下症の一例 Reviewed

三好智子,大塚文男,稲垣謙一,田中康司,越智可奈子,藤井一恭,藤井伸治,当真貴志雄,中村絵里,塚本尚子,武田昌也,三村由香里,小倉俊郎,景山甚郷,槇野博史

日本内分泌学会誌 89 ( Suppl. ) 21 - 23 2013.6

Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens Reviewed

WARREN EH

Blood 115 3869 - 3878 2010.5

Total bacterial counts on oral mucosa after using a commercial saliva substitute in patients undergoing hematopoietic cell transplantation. Reviewed

SIgiura Y, Soga Y, Yamabe K, Tsutani S, Tanimoto I, Maeda H, Kokeguchi S, Fujii N, Ishimaru F, Tanimoto M, Nishimura F, Takashiba S.

Support Care Cancer 2010.5

Total bacterial counts on oral mucosa after using a commercial saliva substitute in patients undergoing hematopoietic cell transplantation Reviewed

Yuko Sugiura, Yoshihiko Soga, Kokoro Yamabe, Soichiro Tsutani, Ichiro Tanimoto, Hiroshi Maeda, Susumu Kokeguchi, Nobuharu Fujii, Fumihiko Ishimaru, Mitsune Tanimoto, Fusanori Nishimura, Shogo Takashiba

SUPPORTIVE CARE IN CANCER 18 ( 3 ) 395 - 398 2010.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

The commercial saliva substitute OralbalanceA (R) has been reported to alleviate symptoms of postradiotherapy xerostomia in head and neck cancer patients. OralbalanceA (R) may also be effective for xerostomia in patients undergoing hematopoietic cell transplantation (HCT) with high-dose chemotherapy and total-body irradiation. However, HCT patients are in a severely compromised condition, and saliva substitute must not promote infection. We reported previously that OralbalanceA (R) has antimicrobial effects against microbial species detected during HCT in vitro. This study was performed to determine the in vivo effects of OralbalanceA (R) on oral mucosal total bacterial counts in patients undergoing HCT.
A total of 18 neutropenic patients undergoing HCT were enrolled in this study. Before and after 1 week of OralbalanceA (R) use, bacterial samples were obtained from patients by wiping an area of I center dot 1 cm on the buccal mucosa with sterilized cotton swabs. Total bacterial counts of the obtained samples were examined by quantitative polymerase chain reaction amplification of the bacterial 16S ribosomal RNA gene. As controls, bacterial samples were also obtained from ten healthy subjects, and total bacterial counts were examined.
No significant increase in bacterial count was observed with use of OralbalanceA (R). None of the patients showed bacterial counts above the range found in healthy controls after using OralbalanceA (R).
In neutropenic patients undergoing HCT, OralbalanceA (R) did not increase the total counts of oral mucosal bacteria beyond the range found in healthy controls. Oral care using OralbalanceA (R) may alleviate the symptoms induced by hyposalivation without promoting infection.

DOI： 10.1007/s00520-009-0789-x

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A distinct subset of self-renewing human memory CD8+T cells survives cytotoxic chemotherapy Reviewed

TURTLE CJ

Immunity 31 834 - 834 2009.11

Efficacy and feasibility of IDEA therapy for refractory or relapsed non-Hodgkin's lymphoma. Reviewed International journal

Hisakazu Nishimori, Nobuharu Fujii, Yoshinobu Maeda, Ken-Ichi Matsuoka, Katsuto Takenaka, Katsuji Shinagawa, Kazuma Ikeda, Keitaro Matsuo, Mine Harada, Mitsune Tanimoto

Anticancer research 29 ( 5 ) 1749 - 54 2009.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The effects of a novel salvage regimen, IDEA (ifosfamide, cytosine arabinoside, etoposide and dexamethasone), which does not include anthracycline or platinum, in patients with non-Hodgkin's lymphoma (NHL) were examined. PATIENTS AND METHODS: Thirty-four patients with refractory or relapsed NHL were treated with IDEA. RESULTS: The overall remission and complete remission rates were 67.6% and 35.3%, respectively. The toxicity of IDEA was tolerable. With a median follow-up of 14 months, one-year overall survival (OS) and progression-free survival rates were 75.1% and 43.7%, respectively. Adequate numbers of CD34(+) cells were obtained in 77.8% of the patients assigned to receive autologous peripheral blood stem cell (PBSC) transplantation. High-dose chemotherapy with autologous PBSC transplantation was carried out in 14 patients; their 3-year OS was 75.0%, with a median follow-up of 38 months. CONCLUSION: IDEA is an effective second-line chemotherapy regimen for NHL patients and has an excellent PBSC-mobilizing effect.

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The effect of adding rituximab to CHOP-based therapy on clinical outcomes for Japanese patients with diffuse large B-cell lymphoma : a propensity score matching analysis Reviewed

NISHIMORI Hisakazu, MATSUO Keitaro, MAEDA Yoshinobu, NAWA Yuichiro, SUNAMI Kazutaka, TOGITANI Kazuto, TAKIMOTO Hidetaka, HIRAMATSU Yasushi, KIGUCHI Toru, YANO Tomofumi, YAMANE Hiromichi, TABAYASHI Takayuki, TAKEUCHI Makoto, MAKITA Masanori, SEZAKI Nobuo, YAMASUJI Yoshiko, SUGIYAMA Haruko, TABUCHI Takahiro, KATAOKA Itaru, FUJII Nobuharu, ISHIMARU Fumihiko, SHINAGAWA Katsuji, IKEDA Kazuma, HARA Masamichi, YOSHINO Tadashi, TANIMOTO Mitsune, the West-Japan Hematology and Oncology Group West-JHOG

Int J Hematol. 89 ( 3 ) 326 - 331 2009.4

Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation Reviewed

HIRAMATSU Yasushi, MAEDA Yoshinobu, FUJII Nobuharu, SAITO Takashi, NAWA Yuichiro, HARA Masamichi, YANO Tomofumi, ASAKURA Shoji, SUNAMI Kazutaka, TABAYASHI Takayuki, MIYATA Akira, MATSUOKA Ken-ichi, SHINAGAWA Katsuji, IKEDA Kazuma, MATSUO Keitaro, TANIMOTO Mitsune, for the West-Japan Hematology and Oncology Group West-JHOG

88 ( 5 ) 588 - 595 2008.12

Evaluation of xerostomia in hematopoietic cell transplantation by a simple capacitance method device. Reviewed International journal

Yuko Sugiura, Yoshihiko Soga, Sachiko Nishide, Kotoe Kono, Kanayo Takahashi, Nobuharu Fujii, Fumihiko Ishimaru, Mitsune Tanimoto, Fusanori Nishimura, Shogo Takashiba

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 16 ( 10 ) 1197 - 200 2008.10

Language：English Publishing type：Research paper (scientific journal)

GOALS: Hematopoietic cell transplantation (HCT) may lead to the development of xerostomia. However, there have been few reports of xerostomia in HCT patients based on objective data. We investigated moisture in the oral mucosa in patients undergoing HCT by the capacitance method using a convenient device, Moisture Checker for Mucus (MCM; Life Co., Ltd., Saitama, Japan). SUBJECTS AND METHODS: Thirty-six patients undergoing HCT at Okayama University Hospital of Medicine and Dentistry (Male = 22, Female = 14; age = 41.6 +/- 16.2 years old) were enrolled in this study. Moisture in the oral mucosa was measured by MCM in accordance with the manufacturer's instructions. The results were obtained as MCM values (%), which are the weight percentage of water content in the oral mucosal epithelium. As controls, moisture of the oral mucosa was also examined in healthy volunteers (Male = 27, Female = 35; age = 43.0 +/- 14.6 years old). MAIN RESULTS: Throughout the examination period, MCM values were significantly lower in patients who underwent HCT than in controls. The degree of mucosal moisture in HCT patients showed wide interindividual differences. CONCLUSION: The degree of mucosal moisture in HCT patients was low and showed wide interindividual differences. Evaluation of xerostomia using such a device may contribute to appropriate oral care with saliva substitute.

DOI： 10.1007/s00520-008-0470-9

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C19orf48 encodes a minor histocompatibility antigen recognized by CD8+ cytotoxic T cells from renal cell carcinoma patients. Reviewed

Tykodi SS, Fujii N, Vigneron N, Lu SM, Mito JK, Miranda MX, Chou J, Voong LN, Thompson JA, Sandmaier BM, Cresswell P, Van den Eynde BJ, Riddell SR, Warren EH.

Clinical Cancer Research 2008.8

DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells Reviewed

Rosinski KV, Fujii N, Mito JK, Koo KK, Xuereb SM, Sala-Torra O, Gibbs JS, Radich JP, Akatsuka Y, Van den Eynde BJ, Riddell SR, Warren EH.

Blood 2008.5

Antimicrobial effects of the saliva substitute, Oralbalance, against microorganisms from oral mucosa in the hematopoietic cell transplantation period. Reviewed International journal

Yuko Sugiura, Yoshihiko Soga, Ichiro Tanimoto, Susumu Kokeguchi, Sachiko Nishide, Kotoe Kono, Kanayo Takahashi, Nobuharu Fujii, Fumihiko Ishimaru, Mitsune Tanimoto, Kokoro Yamabe, Soichiro Tsutani, Fusanori Nishimura, Shogo Takashiba

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 16 ( 4 ) 421 - 4 2008.4

Language：English Publishing type：Research paper (scientific journal)

GOALS: The commercially available saliva substitute Oralbalance has been reported to alleviate symptoms of post-radiotherapy xerostomia in head and neck cancer patients. Oralbalance may also be effective for xerostomia in patients undergoing hematopoietic cell transplantation (HCT) with high-dose chemotherapy and total-body irradiation. However, HCT patients are severely compromised, and saliva substitute must therefore not promote infection. This study was performed to determine the effects of Oralbalance on microbial species identified during HCT. PATIENTS AND METHODS: Microbial identification of oral mucosa was performed in 28 patients undergoing HCT. The antimicrobial effects of Oralbalance against bacteria and fungi detected in the HCT period were examined in vitro. Briefly, bacteria and fungi were spread on agar plates, and 0.1g of Oralbalance gel was applied (about phi1cm). After incubation at 37 degrees C for 24h, the presence of a transparent zone of inhibition around Oralbalance was observed. MAIN RESULTS: Not only bacterial species constituting normal flora of the oral mucosa but also those not usually constituting normal flora, e.g., coagulase-negative Staphylococcus, were detected. A transparent zone was observed around Oralbalance in all bacterial species examined. No transparent zone was observed for Candida albicans, but growth was inhibited in the area where Oralbalance was applied. CONCLUSIONS: Oralbalance does not facilitate increases in microorganisms in the HCT period. Oral care with Oralbalance does not promote infection in patients undergoing HCT.

DOI： 10.1007/s00520-007-0391-z

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Appearance of multidrug-resistant opportunistic bacteria on the gingiva during leukemia treatment. Reviewed International journal

Yoshihiko Soga, Takashi Saito, Fusanori Nishimura, Fumihiko Ishimaru, Junji Mineshiba, Fumi Mineshiba, Hirokazu Takaya, Hideaki Sato, Chieko Kudo, Susumu Kokeguchi, Nobuharu Fujii, Mitsune Tanimoto, Shogo Takashiba

Journal of periodontology 79 ( 1 ) 181 - 6 2008.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Dentists generally recognize the importance of periodontal treatment in patients with leukemia, with the most attention paid to preventing the development of odontogenic infection. For physicians, the worst type of infection is one caused by multidrug-resistant bacteria. Here, we report a patient with an abnormal increase in multidrug-resistant opportunistic bacteria in the gingiva during hematopoietic cell transplantation (HCT). METHODS: A 53-year-old woman receiving HCT for leukemia had an insufficient blood cell count for invasive periodontal treatment before HCT. Even brushing caused difficulties with hemostasis. Therefore, frequent pocket irrigation and local minocycline administration were performed. RESULTS: The multidrug-resistant opportunistic bacterium Stenotrophomonas maltophilia was detected first in phlegm 2 days before HCT, and it was detected in a gingival smear and a blood sample 7 and 11 days after HCT, respectively. The patient developed sepsis on day 11 and died 14 days after HCT. Frequent irrigation and local antibiotic application were ineffective against S. maltophilia on the gingiva. Inflammatory gingiva without scaling and root planing showed bleeding tendency, and this interfered with the eradication of this bacterium. CONCLUSIONS: The gingiva in patients undergoing leukemia treatment acts as sites of proliferation and reservoirs for multidrug-resistant opportunistic bacteria. Severe systemic infection by multidrug-resistant bacteria in such patients with leukemia also may involve the gingiva. To prevent abnormal increases in such bacteria on the gingiva, scaling and/or root planing before chemotherapy, which reduces bleeding on brushing during the neutropenic period caused by chemotherapy, may contribute to infection control in such patients, although it was impossible in this case.

DOI： 10.1902/jop.2008.070205

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Predominant Infiltration of Monocytes in Chronic Graft-Versus-Host Disease Reviewed

Namba Noriko, Shinagawa Katsuji, Fujii Nobuharu, Maeda Yoshinobu, Ishimaru Fumihiko, Ikeda Kazuma, Matsui Toshimitsu, Tanimoto Mitsune, Katayama Yoshio

Transplantation 83 ( 2 ) 220 - 224 2007.1

Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts Reviewed International journal

Kozo Masuda, Akio Hiraki, Nobuharu Fujii, Toshiyuki Watanabe, Motoyuki Tanaka, Kosei Matsue, Yoichiro Ogama, Mamoru Ouchida, Kenji Shimizu, Kazuma Ikeda, Mitsune Tanimoto

CANCER SCIENCE 98 ( 1 ) 102 - 108 2007.1

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL PUBLISHING

Loss or down-regulation of human leukocyte antigen (HLA) class I expression has been demonstrated in a variety of solid tumors. To date, such altered HLA expression has not been studied extensively in freshly isolated leukemic blasts. If it occurs, leukemic cells could escape T-cell surveillance as a consequence. Genotypes of nine leukemic cell lines were determined using a polymerase chain reaction for HLA classes I and II. Cells were also examined for HLA beta 2-microglobulin, and allele-specific HLA protein expression using flow cytometry. Next, 44 samples of freshly isolated leukemic blasts from 43 patients with malignant hematological diseases were examined for allele-specific HLA expression using flow cytometry. Microsatellite analysis was performed to determine heterozygosity in the HLA region on chromosome 6. Genotype analysis for HLA class I together with microsatellite analysis demonstrated loss of HLA haplotype in HL-60 cells. No loss of HLA haplotype was observed in 44 samples of freshly isolated leukemic blasts. As reported previously, flow cytometric analysis rarely demonstrated loss or down-regulation of HLA expression at initial diagnosis (3/39; 7.7%); however, this was evident in two of five cases in relapse (40.0%), which contrasts with previous reports. In one patient with acute leukemia, HLA-A2 cell surface expression was present at initial diagnosis, lost at relapse, and completely restored after 48 h of culture in the presence of interferon-gamma. These results suggest loss of allele-specific HLA expression may be involved in the pathogenesis of relapse in patients with leukemia. The findings should be valuable in designing new strategies for clinical immunotherapy.

DOI： 10.1111/j.1349-7006.2006.00356.x

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Papers - FUJII Nobuharu