Epstein-Barr virus reactivation is a potentially severe complication in chronic lymphocytic leukemia patients with poor prognostic biological markers and fludarabine refractory disease

Rath, Julie; Geisler, Christian H.; Christiansen, Claus; Hastrup, Nina; Madsen, Hans O.; Andersen, Mette K.; Pedersen, Lone Bredo; Jurlander, Jesper

doi:10.3324/haematol.13059

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…We suggest that follow-up of EBV titers of CLL patients should be performed when evolution to RT is suspected, particularly in CLL patients receiving T-cell-suppressing therapy. This hypothesis is supported by a recent report suggesting that EBV reactivation may in fact be an under-diagnosed event in severely immunosuppressed CLL [ 31 ].…”

Section: Discussionsupporting

confidence: 64%

Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients

et al. 2016

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Up to 10 % of chronic lymphocytic leukemia (CLL) patients present with aggressive secondary B-cell lymphoma (most frequently diffuse large B-cell lymphoma, DLBCL) which may be clonally related to the CLL (i.e., Richter transformation, RT, 80 % of the cases) or de novo (20 % of the cases). Several genetic lesions associated with RT have already been identified, but the potential role of the Epstein-Barr virus (EBV) has been largely overlooked.In this study, we describe six CLL patients who developed a secondary EBV-positive (EBV+) B-cell lymphoma (five DLBCL, one Hodgkin lymphoma) and compare their clinicopathological characteristics to ten CLL patients with EBV-negative (EBV−) secondary B-cell lymphomas (all DLBCL).All 16 patients had a history of iatrogenic immunosuppression or chemotherapy. Eighty percent had received fludarabine as part of the CLL treatment. Most secondary lymphomas were clonally related to the previous CLL (3/4 EBV+, 7/7 EBV− cases tested). Notably EBV+ RT was associated with a trend for older age at onset (median 72 vs. 63 years, p value >0.05), longer interval between CLL and RT diagnosis (median 4.2 vs. 2.9 years, p value >0.05), and shorter overall survival (median 4 vs. 10 months, p value >0.05). These differences were not significant, probably due to small sample size. Immunohistochemical profiling suggested more frequent overexpression of TP53 and MYC in EBV− compared to EBV+ secondary lymphoma.Based on this small retrospective single center series, we hypothesize that EBV+ RT may constitute a separate subgroup of RT. Larger series are required to validate this suggestion.Electronic supplementary materialThe online version of this article (doi:10.1007/s12308-016-0273-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 64%

Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients

et al. 2016

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“…All patients with CLL receiving immunosuppressive therapy should be screened for evidence of previous hepatitis B or C infection. Patients positive for hepatitis B surface antigen (HBSAg) or hepatitis B core antigen (HBCAg) may require antiviral treatment and should be managed jointly with a specialist in viral hepatitis (Artz et al , ). EBV reactivation should be considered in febrile CLL patients, especially those with high‐risk disease (Rath et al , ). Progressive multifocal leucoencephalopathy (PML) has been reported as a rare complication in patients with chronic B cell lymphoproliferative disorders who have been treated with rituximab.This diagnosis should be considered in CLL patients who develop progressive confusion, weakness, poor motor coordination, speech or visual changes (Carson et al , ).…”

Section: Supportive Carementioning

confidence: 99%

Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia

et al. 2012

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Epstein–Barr virus reactivation and hemophagocytic lymphohistiocytosis in a patient with chronic lymphocytic leukemia

Lim¹,

Fedoriw

Ramanayake³

et al. 2014

Leukemia & Lymphoma

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A 76-year-old man with asymptomatic stage I chronic lymphocytic leukemia (CLL) diagnosed 20 years previously, on surveillance without any prior therapy, presented to his primary care physician for right foot cellulitis. His medical history included hypertension and diet-controlled diabetes. He was started on levofl oxacin, with clinical improvement. However, 8 days after initiation of therapy, he developed spiking fevers up to 38.9 ° C, non-bilious vomiting and diarrhea, requiring hospitalization. Physical examination revealed jaundice, palpable hepatosplenomegaly and right axillary lymphadenopathy. A complete blood count demonstrated leukocytosis (17.6 ϫ 10 9 /L [normal range: 4.5 -11.0 ϫ 10 9 /L]) with stable persistent lymphocytosis (15.5 ϫ 10 9 /L [normal range: 1.5 -5.0 ϫ 10 9 /L]), anemia (hemoglobin [Hgb] 8.8 g/dL [normal range: 12.0 -16.0 g/dL]) and thrombocytopenia (platelets 75 ϫ 10 9 /L [normal range: 150 -440 ϫ 10 9 /L]). A year previously, his Hgb had been 15.5 g/dL, white blood count 51.9 ϫ 10 9 /L and platelet count 110 ϫ 10 9 /L. A comprehensive metabolic profi le was signifi cant only for hyperbilirubinemia, with a total bilirubin of 2.0 mg/dL (normal range: 0.0 -1.2 mg/dL). Serum creatinine (1.1 mg/dL [normal range: 0.7 -1.3 mg/dL]), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were within normal limits. An ultrasound scan of the right upper quadrant was unremarkable. Th e patient was also found to be hypogammaglobulinemic (serum immunoglobulin A [IgA] 25 mg/dL [normal range: 70 -400 mg/dL], IgG 401 mg/dL [normal range: 700 -1600 mg/dL], IgM Ͻ 21 mg/dL [normal range: 40 -230 mg/dL]). Immunoglobulin levels checked 2 years previously were IgA 32 mg/dL, IgG 798 mg/dL and IgM Ͻ 21 mg/dL. Over the next week, his hospital course was complicated by worsening jaundice (total bilirubin 16.8 mg/dL), elevated liver enzyme levels (AST 629 U/L [normal range: 19 -55 U/L], ALT 234 U/L [normal range: 19 -72 U/L], alkaline phosphatase [ALP] 154 U/L [normal range: 38-126 U/L]), renal dysfunction (creatinine 2.6 mg/dL), bronchopneumonia with positive induced sputum cultures for Klebsiella and Aspergillus and atrial fi brillation requiring direct cardioversion. Additional work-up included signifi cant hyperferritinemia, 13 406 ng/ mL (normal range: 27 -377 ng/mL). At this time, clinical and laboratory fi ndings raised suspicion for hemophagocytic lymphohistiocytosis (HLH). A bone marrow biopsy was performed; however, it was suboptimal for morphologic and immunohistochemical assessment. Th e bone marrow examination revealed a hypercellular marrow (70%), with involvement by CLL, representing 20 -30% of the marrow cellularity. Only rare hemophagocytic forms were identifi ed on the markedly hemodiluted bone marrow aspirate. With regard to the patient ' s CLL, expression of the 70 kDa zeta-associated protein (ZAP-70) and CD38 were negative via fl ow cytometry. Conventional chromosomal analysis of his bone marrow did not reveal any abnormal clone. Fluorescence in situ hybridization (FISH) to...

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Epstein-Barr virus reactivation is a potentially severe complication in chronic lymphocytic leukemia patients with poor prognostic biological markers and fludarabine refractory disease

Cited by 3 publications

References 27 publications

Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients

Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients

Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia

Epstein–Barr virus reactivation and hemophagocytic lymphohistiocytosis in a patient with chronic lymphocytic leukemia

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