Faculty Profiles - FUJII Nobuharu

Papers - FUJII Nobuharu

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Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation Reviewed

Seike K, Fujii N, Asano N, Ohkuma S, Hirata Y , Fujii K, Sando Y, Nakamura M, Naito K , Saeki K, Meguri Y, Asada N, Ennishi D, Nishimori H, Matsuoka K, Tsubaki K, Otsuka F , Maeda Y.

Transfusion 60 ( 3 ) 473 - 478 2020.1

Chemotherapy Improved Pulmonary Arterial Hypertension in a Patient with Chronic-Active Epstein-Barr Virus Infection. Reviewed

Satoshi Akagi, Takashi Miki, Yasuhisa Sando, Nobuharu Fujii, Toshihiro Sarashina, Kazufumi Nakamura, Hiroshi Ito

International heart journal 61 ( 1 ) 191 - 194 2020.1

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

Chronic-active Epstein-Barr virus infection (CAEBV) is a rare disease that can lead to pulmonary arterial hypertension (PAH). However, the treatment for CAEBV-associated PAH has not been established. We discuss a case of improved pulmonary hypertension after chemotherapy in a patient with CAEBV-associated PAH. A 44-year old man was admitted to our hospital because of an abnormal electrocardiogram and liver dysfunction detected by annual medical examination. Echocardiography showed a dilated right ventricle and an estimated right ventricular systolic pressure of 92 mmHg. Right heart catheterization revealed a mean pulmonary arterial pressure of 45 mmHg and pulmonary vascular resistance of 9.8 Wood units. Laboratory examination showed granular lymphocytes and 91% natural killer cells in lymphocyte subsets in peripheral blood. We diagnosed the patient as having CAEBV-associated PAH. After two cycles of chemotherapy without PAH-specific drugs, echocardiography showed improvement in the dilated right ventricle and an estimated right ventricular systolic pressure of 59 mmHg. Right heart catheterization revealed a mean pulmonary arterial pressure of 27 mmHg and pulmonary vascular resistance of 2.4 Wood units. Chemotherapy may improve pulmonary hypertension in patients with CAEBV-associated PAH.

DOI： 10.1536/ihj.19-419

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Prospective Phase 2 Study of Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome Reviewed

Seitaro Terakura, Tetsuya Nishida, Masashi Sawa, Tomonori Kato, Kotaro Miyao, Yukiyasu Ozawa, Akio Kohno, Yasushi Onishi, Noriko Fukuhara, Masanobu Kasai, Nobuharu Fujii, Hisayuki Yokoyama, Hiroatsu Iida, Nobuhiro Kanemura, Atsushi Fujieda, Hiroatsu Ago, Yutaka Tsutsumi, Fumihiko Nakamura, Kazuhiro Yago, Yukiyoshi Moriuchi, Shuichi Ota, Haruhiko Ohashi, Atsumi Yanagisawa, Ritsuro Suzuki, Yachiyo Kuwatsuka, Yoshiko Atsuta, Koichi Miyamura, Makoto Murata

Biology of Blood and Marrow Transplantation 26 ( 1 ) 139 - 144 2020.1

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

Almost comparable transplantation outcomes have been reported with HLA-matched unrelated donor transplantation (UDT) and cord blood transplantation (CBT). We conducted a prospective phase 2 study to assess the efficacy and safety of single-unit myeloablative CBT in adult leukemia and myelodysplastic syndrome. Because the day 180 survival of UDT was approximately 80%, we determined the alternative hypothesis of expected day 180 survival with a successful engraftment rate of 80% and set the null hypothesis of threshold rate at 65%. Sixty-two patients (median age, 37 years) were registered, including 28 with acute myelogenous leukemia, 25 with acute lymphoblastic leukemia, and 9 with myelodysplastic syndrome. Of 61 eligible patients, 52 were successfully engrafted and survived at day 180 (85%; 95% confidence interval, 74% to 93%). Single-unit CBT was judged to be effective because the null hypothesis was rejected (P <. 001). Furthermore, neutrophil engraftment was observed in 57 patients (92%); the incidences of grade II-IV acute and chronic graft-versus-host disease were 30% and 32%, respectively; and the cumulative incidences of nonrelapse mortality and relapse at 2 years were 18% and 13%, respectively. The present study showed favorable survival outcomes with single-unit CBT. Therefore, this method may be considered if a well-HLA-matched UDT cannot be obtained.

DOI： 10.1016/j.bbmt.2019.09.021

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Macrophage elimination in bone marrow by dexamethasone palmitate is associated with successful engraftment in patients with hemophagocytic syndrome. Reviewed

Hiroyuki Sugiura, Ken-Ichi Matsuoka, Masayuki Matsuda, Shuntaro Ikegawa, Tomoko Inomata, Taiga Kuroi, Takeru Asano, Shohei Yoshida, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda

International journal of hematology 110 ( 2 ) 260 - 262 2019.8

Plasma exchange eliminates residual mogamulizumab but does not warrant prompt recovery of peripheral Treg levels. Reviewed International journal

Hiroyuki Sugiura, Ken-Ichi Matsuoka, Yasuhisa Sando, Yusuke Meguri, Shuntaro Ikegawa, Makoto Nakamura, Miki Iwamoto, Takanori Yoshioka, Takeru Asano, Eisei Kondo, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 58 ( 4 ) 472 - 474 2019.8

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

Mogamulizumab (Mog), a humanized anti-CCR4 antibody, provides an important treatment option for relapsed/refractory adult T cell leukemia/lymphoma. However, administration of Mog before allogenic hematopoietic stem cell transplantation has been reported to be a risk factor for severe acute graft-versus-host disease (GVHD). The etiological hypothesis is Mogamulizumab may eradicate CCR4-positive regulatory T cells (Tregs). Theoretically, Treg homeostasis and course of GVHD can be affected by plasma exchange (PE) with decreasing plasma Mog concentration. Here, we present a case of severe acute GVHD after pretransplantation Mog, in which PE was performed for liver failure. As a result, plasma Mog concentration was decreased but it did not lead to the prompt elevation of Treg levels in peripheral blood and clinical responses of GVHD were limited to partial remission. Our case suggests that recovery of donor-derived Treg in the acute phase after HSCT is multifactorial and the single procedure of PE-based Mog depletion does not necessarily warrant the quick restoration of Treg homeostasis.

DOI： 10.1016/j.transci.2019.05.011

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Plasma exchange eliminates residual mogamulizumab but does not warrant prompt recovery of peripheral Treg levels. Reviewed

Sugiura H, Matsuoka K, Sando Y, Meguri Y, Ikegawa S, Nakamura M, Iwamoto M, Yoshioka T, Asano T, Kondo E, Fujii K, Fujii N, Maeda Y.

Transfusion and Apheresis Science. S1473-0502 ( 19 ) 30123 - 30125 2019.7

High dose chemotherapy with autologous stem cell transplantation in primary central nervous system lymphoma: Data from the japan society for hematopoietic cell transplantation (JSHCT) registry Reviewed

Kondo Eisei, Ikeda Takashi, Izutsu Koji, Chihara Dai, Shimizu-Koresawa Risa, Fujii Nobuharu, Sakai Tomoyuki, Kondo Tadakazu, Kubo Kohmei, Kato Yuichi, Akasaka Takashi, Fukuda Takahiro, Ichinohe Tatsuo, Atsuta Yoshiko, Suzumiya Junji, Suzuki Ritsuro

BONE MARROW TRANSPLANTATION 54 453 - 455 2019.7

High-Dose Chemotherapy with Autologous Stem Cell Transplantation in Primary Central Nervous System Lymphoma: Data From the Japan Society for Hematopoietic Cell Transplantation Registry Reviewed

Kondo E, Ikeda T, Izutsu K, Chihara D, Shimizu-Koresawa R, Fujii N, Sakai T, Kondo T, Kubo K, Kato Y, Akasaka T, Fukuda T, Ichinohe T, Atsuta Y, Suzumiya J, Suzuki R; Adult Lymphoma Working Group of the Japan Society for Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant. 25 ( 5 ) 899 - 905 2019.5

Salvage Haploidentical Transplantation Using Low-dose ATG for Early Disease Relapse after First Allogeneic Transplantation: A Retrospective Single-center Review. Reviewed

Sachiyo Okamoto, Ken-Ichi Matsuoka, Maiko Sakamoto, Yoshiaki Usui, Yuki Fujiwara, Takumi Kondo, Katsuma Tani, Kyosuke Saeki, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda

Acta medica Okayama 73 ( 2 ) 161 - 171 2019.4

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

Second allogeneic stem cell transplantation (allo-SCT) is a potentially curative therapy for patients who relapse after first allo-SCT. Human leukocyte antigen (HLA)-haploidentical related donors provide the broad opportunity to conduct second SCT at the appropriate time, but the efficacy of second SCT from haploidentical donors after relapse has not been established. We retrospectively analyzed the records of 33 patients who underwent second SCT. Twenty patients underwent haplo-SCT with low-dose antithymocyte globulin (ATG), and the other 13 patients underwent conventional- SCTs, including HLA-matched related peripheral blood, unrelated bone marrow or cord blood. Three years after the second SCT, the overall survival (OS) and progression-free survival (PFS) of all patients were 32.5% and 23.9%. Multivariate analyses indicated that non-complete response at second SCT, less than 1-year interval to relapse after first- SCT, and total score ≥ 3 on the hematopoietic cell transplantation-specific comorbidity index were significantly associated with a lower PFS rate. The haplo- and conventional- SCT groups showed equivalent results regarding OS, PFS, cumulative incidences of relapse, non-relapse mortality and graft-versus-host disease. The neutropenic period after transplantation was significantly shorter in haplo- SCT than conventional- SCT (10.5 days vs. 16 days, p=0.001). Our analysis revealed that haplo-SCT could be an alternative therapeutic option for relapsed patients after first SCT.

DOI： 10.18926/AMO/56652

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Long-term outcomes in patients treated in the intensive care unit after hematopoietic stem cell transplantation. Reviewed

Makoto Nakamura, Nobuharu Fujii, Kazuyoshi Shimizu, Shuntaro Ikegawa, Keisuke Seike, Tomoko Inomata, Yasuhisa Sando, Keiko Fujii, Hisakazu Nishimori, Ken-Ichi Matsuoka, Hiroshi Morimatsu, Yoshinobu Maeda

International journal of hematology 108 ( 6 ) 622 - 629 2018.12

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

The number of patients who are successfully discharged from the intensive care unit (ICU) after hematopoietic stem cell transplantation (HSCT) remains limited. Most previous studies have evaluated short-term outcomes using ICU mortality; there have been comparatively fewer reports of long-term outcomes. We retrospectively analyzed 39 HSCT patients admitted to the ICU for the first time between April 2008 and July 2014. Performance status was evaluated in four long-term survivors in July 2016. Median age at ICU admission was 54 years (range 30-68). In total, 33 patients (70.2%) required mechanical ventilation and 31 patients (66%) required dialysis. The median OS from first ICU admission was 41 days (95% confidence interval [CI]: 22-64) and the 1-year survival rate was 12.8% (95% CI 4.7-25.2). No statistically significant factors were associated with short-term outcomes. Among long-term outcomes, a second or subsequent HSCT and neutropenia at ICU admission were significant risk factors. Four of 10 ICU survivors have survived with good performance status for a median of 1994 (1203-2633) days. Our results suggest that the number of prior transplants and neutropenia at ICU admission may influence OS.

DOI： 10.1007/s12185-018-2536-x

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Neurolymphomatosis in the cauda Equina Diagnosed by an Open Biopsy. Reviewed

Sasaki R, Ohta Y, Yamada Y, Tadokoro K, Takahashi Y, Sato K, Shang J, Takemoto M, Hishikawa N, Yamashita T, Yasuhara T, Date I, Ikegawa S, Fujii N, Abe K.

Intern Med 57 ( 23 ) 3463 - 3465 2018.12

抗Fybに加え新たに抗KANNOを産生した1症例 Reviewed

池田亮, 小郷博昭, 浅野尚美, 閘結稀, 清家圭介, 三道康永, 中村真, 高木尚江, 藤井敬子, 藤井伸治, 大塚文男

日本輸血細胞治療学会誌 64 ( 6 ) 829 - 830 2018.12

Villous atrophy in the terminal ileum is a specific endoscopic finding correlated with histological evidence and poor prognosis in acute graft-versus-host disease after allo-hematopoietic stem cell transplantation. Reviewed International journal

Yuusaku Sugihara, Sakiko Hiraoka, Nobuharu Fujii, Shiho Takashima, Yasushi Yamasaki, Toshihiro Inokuchi, Masahiro Takahara, Kenji Kuwaki, Keita Harada, Takehiro Tanaka, Hiroyuki Okada

BMC gastroenterology 18 ( 1 ) 111 - 111 2018.7

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

BACKGROUND: Graft-versus-host disease (GVHD) is a common complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Endoscopic biopsy can provide a definitive diagnosis, but the optimal endoscopic approach for diagnosis remains uncertain. This study evaluated whether ileocolonoscopic imaging can predict acute GVHD severity after allo-HSCT. METHODS: Consecutive patients who underwent allo-HSCT were referred to our institution, and those diagnosed with acute GVHD by pathology were included in this retrospective study. RESULTS: Fifty-one of 261 patients who underwent ileocolonoscopy were suspected to have acute intestinal GVHD. We performed univariate and multivariate conditional logistic regression with stepwise variable selection; villous atrophy in the terminal ileum remained a statistically significant predictor of GVHD severity (odds ratio, 4.69; 95% confidence interval, 1.07-20.60, P = 0.04). Patients were classified into three groups based on ileal endoscopic findings in the terminal ileum: group S, GVHD with severe villous atrophy; group M, mild atrophy; and group N, no atrophy. Compared with patients in groups M and N, those in group S had significant clinical GVHD at diagnosis (P = 0.03). In group S, three of four, compared with five of 13 patients in groups M and N, required the addition of second-line agents (P = 0.02). CONCLUSIONS: This study showed that severe atrophy of the terminal ileum predicts severe clinical GVHD that is likely to be refractory to steroid treatment. Thus, the severity of terminal ileum atrophy may serve as a tool in predicting clinically severe GVHD. TRIAL REGISTRATION: Trial Registration Number UMIN 000022805 , Registration date July 1, 2016.

DOI： 10.1186/s12876-018-0829-4

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Adverse Events Associated With Infusion of Hematopoietic Stem Cell Products: A Prospective and Multicenter Surveillance Study. Reviewed International journal

Kazuhiko Ikeda, Hitoshi Ohto, Yoshiki Okuyama, Minami Yamada-Fujiwara, Heiwa Kanamori, Shin-Ichiro Fujiwara, Kazuo Muroi, Takehiko Mori, Kinuyo Kasama, Tohru Iseki, Tokiko Nagamura-Inoue, Nobuharu Fujii, Takashi Ashida, Kazuaki Kameda, Junya Kanda, Asao Hirose, Tsutomu Takahashi, Kazuhiro Nagai, Keiji Minakawa, Ryuji Tanosaki

Transfusion medicine reviews 2018.6

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

Adverse events (AEs) associated with blood transfusions, including component-specific red cell, platelet, and plasma products, have been extensively surveyed. In contrast, surveillance of AEs associated with hematopoietic stem cell (HSC) products in HSC transplantation (HSCT) has been less rigorous, even though HSC products include a diversity of immature and mature hematopoietic cells, substantial plasma, and dimethyl sulfoxide (DMSO) in the case of cryopreserved HSC products. HSC infusion-related AEs have been attributed to DMSO toxicity, but AEs associated with the infusion of noncryopreserved HSC products are not uncommon. To quantify the frequencies, types, and risk factors of HSC infusion-related AEs, we implemented national surveillance for AEs observed within 24 hours after infusion. Herein we report on 1125 HSCTs, including 570 peripheral blood stem cell transplantations (PBSCTs) (290 autologous [auto-] and 280 allogeneic [allo-]), 332 allo-bone marrow transplantations (allo-BMTs) and 223 allo-cord blood transplantations (allo-CBTs). Unexpectedly, incidences of grade ≥ 2 AEs were most frequent in allo-BMTs (37.7%) with no DMSO in any product compared with auto-/allo-PBSCTs (20.9%, P < .001) and allo-CBTs (19.3%, P < .001) typically cryopreserved with DMSO. Hypertension was most often noted in BMTs, whereas nausea/vomiting, fever, and allergic reactions were most frequent in allo-PBSCTs. In a multivariate analysis, a history of transfusion reactions was a risk factor for overall AEs in all HSCTs (odds ratio [OR] = 1.459, P = .045). For grade ≥ 2 AEs in allo-HSCTs, a history of transfusion reactions (OR = 1.551, P = .044) for overall AEs, and high infusion volume (OR = 7.544, P = .005) and allo-PBSCTs (versus BMTs, OR = 9.948, P = .002) for allergic reactions were identified as risk factors. These findings suggest that some factors unrelated to DMSO, such as allo-antigens, contribute to HSC infusion-related AEs. As severe AEs, a total of 117 grade ≥ 3 AEs were reported in 1125 HSCTs, including life-threatening complications in 3 (0.3%) HSCTs: 1 allo-CBT (anaphylaxis) and 2 allo-PBSCTs (hypoxia, kidney injury) with cryopreserved product. Our data show that HSC infusion risks vary by product, can be severe, and should be monitored with the same rigor as modern transfusion hemovigilance programs.

DOI： 10.1016/j.tmrv.2018.05.005

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自己血輸血の変遷貯血式・希釈式・回収式症例数と時代背景を顧みて

藤井敬子, 高木尚江, 清家圭介, 三道康永, 中村真, 閘結稀, 池田亮, 浅野尚美, 小郷博昭, 藤井伸治, 大塚文男

日本輸血細胞治療学会誌 64 ( 2 ) 442 - 442 2018.4

同種造血幹細胞移植後の好中球減少患者に対する顆粒球輸注療法

藤井伸治, 池川俊太郎, 藤井敬子, 佐伯恭昌, 廻勇輔, 浅田騰, 西森久和, 松岡賢市, 大塚文男, 前田嘉信

日本輸血細胞治療学会誌 64 ( 2 ) 453 - 453 2018.4

Progressive multifocal leukoencephalopathy after T-cell replete HLA-haploidentical transplantation with post-transplantation cyclophosphamide graft-versus-host disease prophylaxis. International journal

Shuntaro Ikegawa, Nobuharu Fujii, Koh Tadokoro, Kota Sato, Miki Iwamoto, Masayuki Matsuda, Tomoko Inomata, Hiroyuki Sugiura, Takeru Asano, Shohei Yoshida, Hisakazu Nishimori, Ken-Ichi Matsuoka, Yoshinobu Maeda

Transplant infectious disease : an official journal of the Transplantation Society 20 ( 2 ) e12850 2018.4

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

A 52-year-old man suffered from progressive multifocal leukoencephalopathy (PML) after human leukocyte antigen (HLA)-haploidentical transplantation with post-transplantation cyclophosphamide (PTCY). Mirtazapine, mefloquine, and cytarabine failed to improve his symptoms, and he finally died 4.5 months after PML onset. This is the first case report of a patient with PML after HLA-haploidentical transplantation with PTCY. Although T-cell replete HLA-haploidentical transplantation with PTCY has enabled early immune reconstitution, PML should be considered if a patient's mental condition deteriorates.

DOI： 10.1111/tid.12850

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Progressive multifocal leukoencephalopathy after T-cell replete HLA-haploidentical transplantation with post-transplantation cyclophosphamide graft-versus-host disease prophylaxis. Reviewed

Ikegawa S, Fujii N, Tadokoro K, Sato K, Iwamoto M, Matsuda M, Inomata T, Sugiura H, Asano T, Yoshida S, Nishimori H, Matsuoka KI, Maeda Y.

Transpl Infect Dis 20 ( 2 ) e12850 - e12850 2018.1

Mild renal dysfunction defined by creatinine clearance rate has limited impact on clinical outcomes after allogeneic hematopoietic stem cell transplantation. Reviewed

Ikegawa S, Matsuoka KI, Inomata T, Ikeda N, Sugiura H, Kuroi T, Asano T, Yoshida S, Nishimori H, Fujii N, Kondo E, Maeda Y, Tanimoto M.

International Journal of Hematology 107 ( 5 ) 568 - 577 2018.1

Neurolymphomatosis in the Cauda Equina Diagnosed by an Open Biopsy

Ryo Sasaki, Yasuyuki Ohta, Yuto Yamada, Koh Tadokoro, Yoshiaki Takahashi, Kota Sato, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Takao Yasuhara, Isao Date, Shuntaro Ikegawa, Nobuharu Fujii, Koji Abe

INTERNAL MEDICINE 57 ( 23 ) 3463 - 3465 2018

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Neurolymphomatosis is a rare form of extranodal malignant lymphoma defined as the infiltration of malignant lymphocytes into the central or peripheral nerve. We herein report a case of neurolymphomatosis in the cauda equina diagnosed by an open surgical biopsy. He presented with muscle weakness, atrophy, numbness and hypoesthesia in the bilateral lower extremities with the accumulation of (18)fluoro-2-deoxyglucose (FDG) in the bilateral cauda equina. Cerebrospinal fluid cytology (three times) and flow cytometry (two times) and biopsies of the left rural nerve, bone marrow, paranasal sinus and left testis were all negative for malignancy, so finally we performed a surgical open biopsy of the cauda equina by laminectomy and diagnosed him with diffuse large B-cell lymphoma in the cauda equina. He was successfully treated with the disappearance of the FDG accumulation for a long time. The present case suggested that an early open biopsy of the cauda equina may be considered for cases of suspected neurolymphomatosis in the cauda equina for a good outcome.

DOI： 10.2169/internalmedicine.1049-18

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Papers - FUJII Nobuharu