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Article: [Diagnosis and management of EBV-positive lymphoproliferative disorders].

Arai, Ayako

Rinsho ketsueki] The Japanese journal of clinical hematology

2023 Volume 64, Issue 8, Page(s) 764–771

Abstract: Epstein-Barr virus (EBV) has the ability to immortalize not only B cells but also T and natural killer (NK) cells. The virus may also contribute to the onset of EBV-positive lymphoproliferative disorders (EBV-LPDs) by inducing the introduction of gene ... ...

Abstract	Epstein-Barr virus (EBV) has the ability to immortalize not only B cells but also T and natural killer (NK) cells. The virus may also contribute to the onset of EBV-positive lymphoproliferative disorders (EBV-LPDs) by inducing the introduction of gene mutations. It is known that B cell EBV-LPDs (B-EBV-LPDs) develop with preexisting immunodeficiency, but the onset mechanism of T cell and NK cell EBV-LPDs (T-EBV-LPDs and NK-EBV-LPDs), also known as chronic active EBV disease and associated diseases, is unclear. The diagnosis of both EBV-LPDs requires the quantitative examination of EBV-DNA in the peripheral blood. Eliminating the cause of immunodeficiency or administering rituximab is effective in treating B-EBV-LPDs, but some B-EBV-LPDs and T-EBV-LPDs/NK-EBV-LPDs are resistant to pharmacotherapy. Therefore, further research is needed to explicate the pathophysiology of EBV-LPDs and develop a drug for its treatment.
MeSH term(s)	Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/diagnosis ; Epstein-Barr Virus Infections/therapy ; B-Lymphocytes ; Killer Cells, Natural ; Lymphoproliferative Disorders/diagnosis ; Lymphoproliferative Disorders/etiology ; Lymphoproliferative Disorders/therapy
Language	Japanese
Publishing date	2023-08-10
Publishing country	Japan
Document type	English Abstract ; Journal Article
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
DOI	10.11406/rinketsu.64.764
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Zs.A 1175: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 535: Show issues

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Article: Chronic Active Epstein-Barr Virus Infection: The Elucidation of the Pathophysiology and the Development of Therapeutic Methods.

Arai, Ayako

Microorganisms

2021 Volume 9, Issue 1

Abstract: Chronic active Epstein-Barr virus infection (CAEBV) is a disease where Epstein-Barr virus (EBV)-infected T- or NK-cells are activated and proliferate clonally. The symptoms of this dual-faced disease include systemic inflammation and multiple organ ... ...

Abstract	Chronic active Epstein-Barr virus infection (CAEBV) is a disease where Epstein-Barr virus (EBV)-infected T- or NK-cells are activated and proliferate clonally. The symptoms of this dual-faced disease include systemic inflammation and multiple organ failures caused by the invasion of infected cells: inflammation and neoplasm. At present, the only effective treatment strategy to eradicate EBV-infected cells is allogeneic stem cell transplantation. Lately, the investigation into the disease's pathogenic mechanism and pathophysiology has been advancing. In this review, I will evaluate the new definition in the 2017 WHO classification, present the advancements in the study of CAEBV, and unfold the future direction.
Language	English
Publishing date	2021-01-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9010180
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: [The road to treating chronic active Epstein-Barr viral infection].

Arai, Ayako

Rinsho ketsueki] The Japanese journal of clinical hematology

2021 Volume 62, Issue 7, Page(s) 835–845

Abstract: Chronic active Epstein-Barr virus (CAEBV) infection is a progressive disease characterized by persistent inflammatory symptoms accompanied by clonally proliferating EBV-positive T or NK cells. The optimal medical treatment for CAEBV to eradicate EBV- ... ...

Abstract	Chronic active Epstein-Barr virus (CAEBV) infection is a progressive disease characterized by persistent inflammatory symptoms accompanied by clonally proliferating EBV-positive T or NK cells. The optimal medical treatment for CAEBV to eradicate EBV-infected T or NK cells has not yet been established, with allogeneic hematopoietic stem cell transplantation as the only strategy currently available. Patients with CAEBV have been reported mainly from limited area of Japan and East Asia. However, CAEBV is drawing a global attention, and the number of reports is increasing worldwide after its definition was added to the EBV-positive T- or NK-cell neoplasms in the 2017 World Health Organization classification. We had previously discovered that STAT3 was constitutively activated in EBV-infected tumor cells in CAEBV inducing the immortalization and production of inflammatory cytokines. Based on these findings, an investigator-initiated clinical research of a JAK1/2 inhibitor ruxolitinib for CAEBV infection was initiated in January 2019. Japanese researchers have been expected to elucidate pathological mechanisms and to establish an effective treatment.
MeSH term(s)	Chronic Disease ; Epstein-Barr Virus Infections/drug therapy ; Hematopoietic Stem Cell Transplantation ; Herpesvirus 4, Human ; Humans ; Japan ; Killer Cells, Natural
Language	Japanese
Publishing date	2021-08-04
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
DOI	10.11406/rinketsu.62.835
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Article: Chronic Active Epstein–Barr Virus Infection: The Elucidation of the Pathophysiology and the Development of Therapeutic Methods

Arai, Ayako

Microorganisms. 2021 Jan. 15, v. 9, no. 1

2021

Abstract: Chronic active Epstein–Barr virus infection (CAEBV) is a disease where Epstein–Barr virus (EBV)-infected T- or NK-cells are activated and proliferate clonally. The symptoms of this dual-faced disease include systemic inflammation and multiple organ ... ...

Abstract	Chronic active Epstein–Barr virus infection (CAEBV) is a disease where Epstein–Barr virus (EBV)-infected T- or NK-cells are activated and proliferate clonally. The symptoms of this dual-faced disease include systemic inflammation and multiple organ failures caused by the invasion of infected cells: inflammation and neoplasm. At present, the only effective treatment strategy to eradicate EBV-infected cells is allogeneic stem cell transplantation. Lately, the investigation into the disease’s pathogenic mechanism and pathophysiology has been advancing. In this review, I will evaluate the new definition in the 2017 WHO classification, present the advancements in the study of CAEBV, and unfold the future direction.
Keywords	Human gammaherpesvirus 4 ; cell transplantation ; classification ; infection ; inflammation ; microorganisms ; pathophysiology ; stem cells
Language	English
Dates of publication	2021-0115
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9010180
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Chronic active Epstein-Barr virus infection: a bi-faceted disease with inflammatory and neoplastic elements.

Arai, Ayako

Immunological medicine

2019 Volume 41, Issue 4, Page(s) 162–169

Abstract: Chronic active Epstein-Barr virus infection (CAEBV) is one of the Epstein-Barr virus (EBV)-positive T- or NK-cell lymphoproliferative diseases. It is characterized by clonal proliferation of EBV-infected T or NK cells and their infiltration into systemic ...

Abstract	Chronic active Epstein-Barr virus infection (CAEBV) is one of the Epstein-Barr virus (EBV)-positive T- or NK-cell lymphoproliferative diseases. It is characterized by clonal proliferation of EBV-infected T or NK cells and their infiltration into systemic organs, leading to their failure. Inflammatory symptoms, fever, lymphadenopathy and liver dysfunction are main clinical findings of CAEBV. EBV itself contributes to the survival of the host cells via induction of CD40 and CD137 expression and constitutive activation of NF-κB. Accumulation of gene mutations in the infected cells may lead to the development of highly malignant lymphoma or leukemia. Furthermore, constitutive activation of STAT3 is detected in the infected cells, which not only promotes cell survival but also enhances production of inflammatory cytokines. Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only effective treatment strategy for eradication of EBV-infected T or NK cells. However, active disease at the time of allo-HSCT (defined as presence of fever, liver dysfunction, progressive skin lesions, vasculitis or uveitis) is a negative prognostic factor. Establishment of chemotherapy regimens for effective resolution of disease activity in patients with CAEBV is a key imperative. Based on the recently unraveled molecular mechanisms CAEBV development, pathways mediated by NF-κB or JAK/STAT are potential novel therapeutic targets.
Language	English
Publishing date	2019-01-31
Publishing country	England
Document type	Journal Article
ISSN	2578-5826
ISSN (online)	2578-5826
DOI	10.1080/25785826.2018.1556030
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Article: Advances in the Study of Chronic Active Epstein-Barr Virus Infection: Clinical Features Under the 2016 WHO Classification and Mechanisms of Development.

Arai, Ayako

Frontiers in pediatrics

2019 Volume 7, Page(s) 14

Abstract: Chronic active Epstein-Barr virus infection (CAEBV) is one of the Epstein-Barr virus (EBV)-positive T- or NK-lymphoproliferative diseases. It is considered rare and geographically limited to Japan and East Asia. However, CAEBV is drawing international ... ...

Abstract	Chronic active Epstein-Barr virus infection (CAEBV) is one of the Epstein-Barr virus (EBV)-positive T- or NK-lymphoproliferative diseases. It is considered rare and geographically limited to Japan and East Asia. However, CAEBV is drawing international attention, and the number of case reported worldwide is increasing, after its classification in the EBV-positive T- or NK-cell neoplasms, in the 2016 WHO classification. In this article, I review current advances in the study of CAEBV under the new definition and show future directions. In CAEBV, EBV-infected T or NK cells clonally proliferate and infiltrate multiple organs, leading to their failure. These characteristics define CAEBV as a lymphoid neoplasm. However, the main symptom of CAEBV is inflammation. Recently, the mechanisms underlying the development of CAEBV have gradually become clearer. EBV infection of T or NK cells can occur during the acute phase of primary infection with a high EBV load in the peripheral blood. In addition, it was reported that cytotoxic T cells decreased in numbers or showed dysfunction in CAEBV. These findings suggest that undetermined immunosuppressive disorders may underlie persistent infection of T or NK cells. Furthermore, EBV itself contributes to the survival of host cells.
Language	English
Publishing date	2019-02-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2019.00014
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Article ; Online: Quantitative evaluation of treatment response to lenalidomide by applying fluorescence in situ hybridization for peripheral blood granulocytes in a patient with 5q- syndrome.

Sakai, Hirotaka / Miura, Ikuo / Arai, Ayako

Journal of clinical and experimental hematopathology : JCEH

2022 Volume 62, Issue 3, Page(s) 158–163

Abstract: The introduction of lenalidomide has significantly improved clinical outcomes in myelodysplastic syndrome (MDS) with isolated interstitial deletion of the long arm of chromosome 5 (del(5q)) (5q- syndrome). These days, MDS with isolated del(5q) includes ... ...

Abstract	The introduction of lenalidomide has significantly improved clinical outcomes in myelodysplastic syndrome (MDS) with isolated interstitial deletion of the long arm of chromosome 5 (del(5q)) (5q- syndrome). These days, MDS with isolated del(5q) includes cases with one additional chromosome abnormality other than monosomy 7 or del(7q), and so we need a better way to monitor tumor cells in each patient than the clinical parameters used to date. An 82-year-old woman with MDS with isolated del(5q) was treated with lenalidomide daily for 21 days in a 4-week cycle. Fluorescence in situ hybridization with CSF1R located at 5q was applied to the peripheral blood samples. Because mature lymphocytes are not involved in the MDS clone, based on the nuclear morphology, polymorphonuclear cells (PMNs) and round-shaped nuclear cells (RSNs) were separately evaluated during treatment. After a single course of treatment, the number of PMNs with del(5q) decreased; by the end of the second course of treatment, both PMNs and RSNs with del(5q) had disappeared. The dynamics of 5q- PMNs is a simple but rapid and reliable indicator to confirm the effect of lenalidomide in MDS with del(5q).
MeSH term(s)	Aged, 80 and over ; Anemia, Macrocytic ; Chromosome Deletion ; Chromosomes, Human, Pair 5/genetics ; Cri-du-Chat Syndrome ; Female ; Granulocytes/pathology ; Humans ; In Situ Hybridization, Fluorescence ; Lenalidomide/therapeutic use ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/pathology ; Thalidomide/therapeutic use ; Trisomy
Chemical Substances	Thalidomide (4Z8R6ORS6L) ; Lenalidomide (F0P408N6V4)
Language	English
Publishing date	2022-06-22
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	2395568-5
ISSN	1880-9952 ; 1880-9952
ISSN (online)	1880-9952
ISSN	1880-9952
DOI	10.3960/jslrt.22001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: [Overview].

Arai, Ayako

Rinsho ketsueki] The Japanese journal of clinical hematology

2015 Volume 56, Issue 3, Page(s) 245

MeSH term(s)	Animals ; Disease Models, Animal ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
Language	Japanese
Publishing date	2015-03
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
DOI	10.11406/rinketsu.56.245
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Zs.A 1175: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: [Molecular mechanisms of Epstein-Barr virus-induced lymphoid neoplasms].

Arai, Ayako

Rinsho ketsueki] The Japanese journal of clinical hematology

2015 Volume 56, Issue 3, Page(s) 269–277

Abstract: Epstein-Barr virus (EBV) infects human beings and latently persists in B-cells throughout life. EBV infection renders B cells immortal. In immunocompetent individuals, the expansion of EBV-infected B-cells is suppressed by cytotoxic T lymphocytes (CTL). ... ...

Abstract	Epstein-Barr virus (EBV) infects human beings and latently persists in B-cells throughout life. EBV infection renders B cells immortal. In immunocompetent individuals, the expansion of EBV-infected B-cells is suppressed by cytotoxic T lymphocytes (CTL). However, once immunosuppression-induced CTL dysfunction or accelerated proliferation of infected cells due to gene mutation accumulation occurs, the infected cells proliferate leading to B-cell neoplasms. The products of the viral genome, i.e. LMP1, EBNA2, EBNA3A, and EBNA3C, are indispensable for transformation of infected B-cells. These viral proteins suppress apoptosis of the infected cells and contribute to the expansion of genetic mutation-bearing clones. It was recently reported that EBV also infects T or NK cells, suppresses their apoptosis, and promotes their survival by inducing CD40 and CD137 expressions. These results indicate that EBV may contribute to the development EBV-positive T- or NK-cell neoplasms. EBV-positive lymphoid neoplasms are generally resistant to chemotherapy and patient outcomes have thus been poor. Clarification of the molecular mechanisms underlying disease development is anticipated to lead to the establishment of novel treatment strategies.
MeSH term(s)	Animals ; B-Lymphocytes/virology ; Epstein-Barr Virus Infections/diagnosis ; Epstein-Barr Virus Infections/virology ; Herpesvirus 4, Human/isolation & purification ; Humans ; Lymphoma/virology ; T-Lymphocytes, Cytotoxic/virology ; Viral Matrix Proteins/metabolism
Chemical Substances	Viral Matrix Proteins
Language	Japanese
Publishing date	2015-03
Publishing country	Japan
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
DOI	10.11406/rinketsu.56.269
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Article ; Online: Aortitis after administration of pegfilgrastim to a healthy donor for peripheral blood stem cell collection.

Uemura, Yu / Oshima, Kumi / Fuseya, Aika / Hosokai, Akane / Ohashi, Ayaka / Kanno, Masatoshi / Arai, Ayako

International journal of hematology

2023 Volume 118, Issue 6, Page(s) 772–775

Abstract: A 45-year-old man who was a sibling donor for allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was administered 7.2 mg of pegfilgrastim for stem cell collection. Peripheral blood stem cells were collected 4 days after administration of ... ...

Abstract	A 45-year-old man who was a sibling donor for allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was administered 7.2 mg of pegfilgrastim for stem cell collection. Peripheral blood stem cells were collected 4 days after administration of pegfilgrastim (Day 4) and 4.32 × 10
MeSH term(s)	Male ; Humans ; Middle Aged ; Granulocyte Colony-Stimulating Factor/adverse effects ; Aortitis/therapy ; Aortitis/chemically induced ; Peripheral Blood Stem Cells ; Filgrastim/adverse effects ; Hematopoietic Stem Cell Transplantation
Chemical Substances	pegfilgrastim (3A58010674) ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; Filgrastim (PVI5M0M1GW)
Language	English
Publishing date	2023-08-14
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	1076875-0
ISSN	1865-3774 ; 0917-1258 ; 0925-5710
ISSN (online)	1865-3774
ISSN	0917-1258 ; 0925-5710
DOI	10.1007/s12185-023-03649-0
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