Faculty Profiles - FUJII Keiko

Papers - FUJII Keiko

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

Sugiura H, Matsuoka KI, 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 58 ( 4 ) 472 - 474 2019.7

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

Okamoto S, Matsuoka KI, Sakamoto M, Usui Y, Fujiwara Y, Kondo T, Tani K, Saeki K, Meguri Y, Asada N, Ennishi D, Nishimori H, Fujii K, Fujii N, Maeda Y

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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Predictors of vasovagal reactions during preoperative autologous blood donation: a single-institution analysis. Reviewed

Hisakazu Nishimori, Nobuharu Fujii, Keiko Fujii, Tohru Ikeda, Naomi Asano, Hiroaki Ogo, Miwa Yamakawa, Naoe Takagi, Fumio Otsuka, Kazuma Ikeda

International journal of hematology 105 ( 6 ) 812 - 818 2017.6

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

Studies examining risk factors associated with vasovagal reactions (VVRs) during autologous blood donations, especially in younger subjects, have been limited. The aim of the present study was to define risk factors for VVRs during preoperative autologous blood donation in patients, including those younger than 18 years old. We retrospectively analyzed 4192 autologous, preoperative blood donations between 2007 and 2015 at Okayama University Hospital. Eighty-seven (2.08%) of the patients experienced VVRs. VVRs occurred approximately three times as often in patients 0-17 years old (16/320, 5.0%) than in patients 18 years and older (71/3872, 1.8%). In particular, VVRs occurred more frequently in those 10-13 years old, and decreased with older age (P = 0.006). In a univariate analysis, younger age, lower body mass index, lower systolic blood pressure, lower body weight, lower total blood volume, female gender, first-time collection, and higher heart rate were associated with a higher incidence of VVRs. In a multivariate analysis, lower systolic blood pressure (P < 0.001), higher heart rate (P = 0.007), and first-time collection (P = 0.015), remained independent predictors of VVRs. These results emphasize the need for careful attention during blood collection.

DOI： 10.1007/s12185-017-2204-6

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Graft-versus-leukemia effect with a WT1-specific T-cell response induced by azacitidine and donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation. Reviewed International journal

Tatsunori Ishikawa, Nobuharu Fujii, Masahide Imada, Michinori Aoe, Yusuke Meguri, Tomoko Inomata, Hiromi Nakashima, Keiko Fujii, Shohei Yoshida, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Mitsune Tanimoto

Cytotherapy 19 ( 4 ) 514 - 520 2017.4

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

BACKGROUND: Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. CASE REPORT: Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation. We observed a powerful graft-versus-leukemia (GVL) effect accompanied by an evident Wilms tumor antigen 1 (WT1)-specific CD8 T-cell response. Remission continued for 15 months, but finally the patient relapsed. The kinetics of the WT1-specific CD8 T cells were inversely associated with WT1 messenger RNA (mRNA), suggesting a WT1-driven GVL effect. DISCUSSION: A difference of T-cell phenotype between the whole T cells and the WT1-specific CD8 T cells was observed. It is of note that the memory phenotype of the WT1-specific T cell was limited and decreased early. The immunoescape mechanism was partly supported by loss of the memory phenotype due to failure of expansion and differentiation. CONCLUSION: Our data suggested that a WT1-specific T-cell response at least partly contributes to the GVL effect induced by Aza + DLI. A strategy for maximizing and maintaining the memory phenotype of the CTL may be required for durable remission.

DOI： 10.1016/j.jcyt.2016.12.007

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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

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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TRANSFUSION IN LUNG TRANSPLANTATION AT OKAYAMA UNIVERSITY HOSPITAL Reviewed

ASANO Naomi, IKEDA Toru, OGO Hiroaki, FUJII Keiko, SUGIYAMA Haruko, IKEDA Kazuma, KOIDE Norio

Journal of the Japan Society of Blood Transfusion 56 ( 5 ) 606 - 611 2010.10

Language：Japanese Publisher：The Japan Society of Transfusion Medicine and Cell Therapy

As of March 2009, 67 lung transplants, including 52 from living donors and 15 from cadaveric donors, have been carried out since the first lung transplantation in Japan in 1998 at Okayama University Hospital. We analyzed the preparation and actual usage of blood products in lung transplantation during this period.<br> The average number of units of prepared and transfused red cells were 57.4 and 33.5, respectively, with a C/T ratio of 1.73. Average number of units of prepared and transfused fresh frozen plasma were 43.3 and 19.4, and those of platelet concentrate were 27.7 and 19.8, respectively. In double- and single-lung transplantation, the average number of units of transfused red cells, fresh frozen plasma and platelet concentrate were 37.9 and 11.5 (p<0.05), 21.8 and 7.0 (p<0.05), and 22.8 and 4.5 (p<0.05), respectively. In 5 double-lung transplants, more than 100 units of red blood cells were prepared, of which 3 were from cadaveric donors.<br> It is difficult to predict bleeding volume during lung transplantation due to factors including the degree of adhesion between visceral and parietal pleura. Our analysis suggested that the number of units of blood products required might depend on whether transplantation is single-lung or double-lung, probably indicating that cardiopulmonary bypass usage is a major determinant. Our analysis confirmed that it is important for both transfusion and clinical departments to communicate with each other on a routine basis, and to be prepared to use ABO-mismatched but compatible blood products in order to handle emergency surgery for cadaveric lung transplantation with demand for a large amount of blood products.<br>

DOI： 10.3925/jjtc.56.606

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Other Link： http://search.jamas.or.jp/link/ui/2011048595

Plasma stromal cell-derived factor-1 during granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization Reviewed

T. Kozuka, F. Ishimaru, K. Fujii, K. Masuda, K. Kaneda, T. Imai, N. Fujii, H. Ishikura, S. Hongo, T. Watanabe, K. Shinagawa, K. Ikeda, K. Niiya, M. Harada, M. Tanimoto

Bone Marrow Transplantation 31 ( 8 ) 651 - 654 2003.4

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

In this report, we examined plasma stromal cell-derived factor-1 levels in normal healthy donors for allogeneic peripheral blood stem cell transplantation (PBSCT) and in patients for autologous PBSCT using an enzyme-linked immunosorbent assay. The average level of plasma stromal cell-derived factor-1 was 2197pg/ml before granulocyte colony-stimulating factor administration and 1899 pg/ml on day 4, demonstrating a significant decrease in the peripheral blood of healthy donors (P = 0.0003). In patients for autologous PBSCT, a significant decrease of plasma stromal cell-derived factor-1 in the peripheral blood was also observed (P = 0.0464). However, the physiologic gradient of stromal cell-derived factor-1 between peripheral blood and bone marrow was never inverted in normal healthy donors or in autologous PBSCT patients. Our results suggest that stromal cell-derived factor-1 may not be involved in the granulocyte colony-stimulating factor-induced release of CD34+ cells to the peripheral blood. Further studies of a possible additive effect of granulocyte colony-stimulating factor and stromal cell-derived factor-1 are warranted.

DOI： 10.1038/sj.bmt.1703901

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Risk of neutropenic fever and early infectious complications after autologous peripheral blood stem cell transplantation for malignant diseases. Reviewed International journal

Fujii K, Aoyama M, Shinagawa K, Matsuo K, Takenaka K, Ikeda K, Kojima K, Ishimaru F, Kiura K, Ueoka H, Niiya K, Tanimoto M, Harada M

Int J Hematol 76 ( 2 ) 186 - 191 2002.8

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