Chronic active Epstein-Barr virus infection: a novel cause of lymphocytic variant hypereosinophilic syndrome

Klion, Amy D.; Mejia, Rojelio; Cowen, Edward W.; Dowdell, Kennichi C.; Dunleavy, Kieron; Fahle, Gary A.; Holland-Thomas, Nicole; Marić, Irina; Pittaluga, Stefania; Raffeld, Mark; Santos, Carlo; Stetler‐Stevenson, Maryalice; Krogmann, Tammy; Shatzer, Amber N.; Turk, Siu-Ping; Yin, Yuzhi; Xi, Liqiang; Prussin, Calman; Cohen, Jeffrey I.

doi:10.1182/blood-2012-12-472720

Cited by 26 publications

(12 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A case of lymphocyte‐variant hypereosinophilia was reported in a patient with chronic active Epstein‐Barr virus infection, and an EBV‐infected T‐cell clone producing eosinophilopoietic cytokines. Slightly elevated EBV DNA levels were detected in two of an additional 15 lymphocyte‐variant hypereosinophilia patients tested, but the causal relationship EBV and this subtype of eosinophilia is unclear . Recently, STAT3 Y640F mutation and overexpression of STAT3 gene targets were reported in patients with lymphocyte‐variant hypereosinophilia, leading to the production of eosinophil‐promoting Th2 cytokines …”

Section: Diagnosismentioning

confidence: 99%

World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management

2019

View full text Add to dashboard Cite

Disease overview: The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary or clonal) disorders with potential for end-organ damage.Diagnosis: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 10 9 /L, and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ-hybridization, flow immunophenotyping, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm. Risk stratification: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes. This includes the major category "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2", and the MPN subtype, "chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS). Lymphocyte-variant hypereosinophilia is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.Risk-adapted therapy: The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (eg, <1.5 × 10 9 /L) without symptoms or signs of organ involvement, a watch and wait approach with close-follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES. Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. The use of antibodies against interleukin-5 (IL-5) (mepolizumab), the IL-5 receptor (benralizumab), as well as other targets on eosinophils remains an active area of investigation.

show abstract

Section: Diagnosismentioning

confidence: 99%

World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management

2019

View full text Add to dashboard Cite

show abstract

“…Other immunomodulatory/T-cell-directed strategies tried have included IFN-a, hydroxyurea, and lenalidomide, none of which have shown robust success. 30 HSP90 inhibitors have also been shown to kill EBV-infected B cells and T cells by reducing the levels of EBV EBNA1 and LMP1. In 1 study, treatment of cells with the HSP90 ganetespib also reduced the level of phosphorylated Akt, delayed the onset of EBV 1 B-cell lymphoma, and prolonged survival in SCID mice.…”

Section: Targeting the Ebv-infected T Cellsmentioning

confidence: 99%

How I treat T-cell chronic active Epstein-Barr virus disease

Bollard

Cohen

2018

Blood

Self Cite

View full text Add to dashboard Cite

T-cell chronic active Epstein-Barr virus (CAEBV) is a rare disease in which EBV is present predominantly in T cells that infiltrate the tissues; patients have high levels of EBV in the blood. If untreated, patients often develop liver failure, hemophagocytic lymphohistiocytosis, coronary artery aneurysms, EBV infiltrating T cells impairing organ function, or T-cell lymphomas refractory to treatment. At present, hematopoietic stem-cell transplantation is the only curative therapy, and it is critical to make a proper diagnosis and initiate transplantation before the disease progresses to an irreversible stage. Specific medications such as high-dose systemic corticosteroids or ganciclovir combined with either histone deacetylase inhibitors or bortezomib may temporarily reduce systemic toxicity associated with T-cell CAEBV and allow the patient time to receive a transplant. Relapses of the disease after transplantation have also occurred, and the use of donor-derived virus-specific T cells may help to treat these relapses.

show abstract

“…A case of lymphocyte‐variant hypereosinophilia was reported in a patient with chronic active Epstein‐Barr virus infection and an EBV‐infected T‐cell clone producing eosinophilopoietic cytokines. Slightly elevated EBV DNA levels were detected in 2 of an additional 15 lymphocyte‐variant hypereosinophilia patients tested, but the causal relationship EBV and this subtype of eosinophilia is unclear .…”

Section: Diagnosismentioning

confidence: 99%

World Health Organization‐defined eosinophilic disorders: 2015 update on diagnosis, risk stratification, and management

Gotlib¹

2015

American J Hematol

102

109

View full text Add to dashboard Cite

Disease overview: The eosinophilias encompass a broad range of non‐hematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end‐organ damage. Diagnosis: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1,500/mm3 and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ‐hybridization, flow immunocytometry, and T‐cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder. Risk stratification: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2008 World Health Organization establishes a semi‐molecular classification scheme of disease subtypes including ‘myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1’, chronic eosinophilic leukemia, not otherwise specified, (CEL, NOS), lymphocyte‐variant hypereosinophilia, and idiopathic hypereosinophilic syndrome (HES), which is a diagnosis of exclusion. Risk‐adapted therapy: The goal of the therapy is to mitigate eosinophil‐mediated organ damage. For patients with milder forms of eosinophilia (e.g. < 1,500/mm3) without symptoms or signs of organ involvement, a watch and wait approach with close‐follow‐up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first‐line therapy for patients with lymphocyte‐variant hypereosinophilia and HES. Hydroxyurea and interferon‐alpha have demonstrated efficacy as initial treatment and steroid‐refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents and hematopoietic cell transplant have been used for aggressive forms of HES and CEL with outcomes reported for limited numbers of patients. Although clinical trials have been performed with anti IL‐5 (mepolizumab) and anti‐CD52 (alemtuzumab) antibodies, their therapeutic role in primary eosinophilic diseases and HES has yet to be established. Am. J. Hematol. 90:1077–1089, 2015. © 2015 Wiley Periodicals, Inc.

show abstract

Chronic active Epstein-Barr virus infection: a novel cause of lymphocytic variant hypereosinophilic syndrome

Cited by 26 publications

References 4 publications

World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management

World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management

How I treat T-cell chronic active Epstein-Barr virus disease

World Health Organization‐defined eosinophilic disorders: 2015 update on diagnosis, risk stratification, and management

Contact Info

Product

Resources

About