HCV-related lymphoproliferative disorders in the direct-acting antivirals era: from mixed cryoglobulinemia to B-cell lymphoma

This report describes a case of concomitant treatment of advanced diffuse large B-cell lymphoma with chemoimmunotherapy along with direct-acting antivirals for hepatitis C virus in a patient coinfected with HIV. The patient tolerated gemcitabine, dexamethasone, cisplatin, and rituximab and achieved sustained virologic response after treatment with ledipasvir/sofosbuvir.

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Direct-acting antivirals in relapsed or refractory hepatitis C virus-associated diffuse large B-cell lymphoma

Leukemia & Lymphoma ◽

10.1080/10428194.2020.1755859 ◽

2020 ◽

Vol 61 (9) ◽

pp. 2122-2128 ◽

Cited By ~ 4

Author(s):

Michele Merli ◽

Irene Defrancesco ◽

Carlo Visco ◽

Caroline Besson ◽

Alice Di Rocco ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Direct Acting Antivirals ◽

Large B Cell Lymphoma ◽

Direct Acting ◽

Large B Cell

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Response to Interferon-Free Direct Antivirals (DAAS) Treatment in HCV-Related Subcutaneous Lipoma-Like Marginal Zone B-Cell Lymphoma

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2019.053 ◽

2019 ◽

Vol 11 (1) ◽

pp. e2019053 ◽

Cited By ~ 1

Author(s):

Maria Lucia De Luca ◽

Laura Lombardi ◽

Germana Tartaglia ◽

Francesca Fazio ◽

Alessio Di Prima ◽

...

Keyword(s):

B Cell ◽

Antiviral Therapy ◽

Virological Response ◽

Marginal Zone ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Rare Entity ◽

Direct Acting Antivirals ◽

Direct Acting ◽

Subcutaneous Lipoma

In 2010 a new entity termed “lipoma-like” HCV related marginal zone B-NHL was described. The etiological link between HCV infection and B-NHL has been extensively investigated in several epidemiological, biological and therapeutic studies and large experiences in literature demonstrated indolent lymphoma’s regression after antiviral therapy. HCV-related indolent NHL response to interferon-ribavirin-based antiviral therapy is well documented, while evidence of the efficacy of interferon-free direct-acting antivirals (DAAs) in this subset of lymphoma is also currently increasing. In this article we report two cases of HCV-related subcutaneous “lipoma-like” Marginal Zone B-cell lymphoma, treated with DAAs. Sustained virological response (SVR) with reduction of MZL localizations, persisting to date, were obtained in both patients. These data originally demonstrate the efficacy of DAAs in this rare entity.

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Concomitant therapy with direct-acting antivirals and chemoimmunotherapy in HCV-associated diffuse large B-cell lymphoma

Digestive and Liver Disease ◽

10.1016/j.dld.2018.10.019 ◽

2019 ◽

Vol 51 (5) ◽

pp. 719-723 ◽

Cited By ~ 5

Author(s):

Vincenzo Occhipinti ◽

Lucia Farina ◽

Mauro Viganò ◽

Marco Capecchi ◽

Sara Labanca ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Direct Acting Antivirals ◽

Concomitant Therapy ◽

Large B Cell Lymphoma ◽

Direct Acting ◽

Large B Cell

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Successful treatment by on-demand glecaprevir and pibrentasvir for hepatitis C flare during R-CHOP in patients with diffuse large B-cell lymphoma: a case report

BMC Infectious Diseases ◽

10.1186/s12879-021-06091-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Machiko Umemura ◽

Goki Suda ◽

Shihori Tsukamoto ◽

Ko Ebata ◽

Shinjiro Takahash ◽

...

Keyword(s):

Hepatitis C ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Direct Acting Antivirals ◽

On Demand ◽

Large B Cell Lymphoma ◽

First Case ◽

Direct Acting ◽

Large B Cell

Abstract Background In patients with hepatitis C virus (HCV) and malignant lymphoma, hepatitis C flare during R-CHOP can result in discontinuation of treatment. However, appropriate therapeutic strategies for managing hepatitis C flare during R-CHOP have not been established, and this issue is complicated by conflicting results regarding the use of direct-acting antivirals in patients with uncontrolled malignancies. Case presentation We report the first case of effective and safe treatment with on-demand 8-week glecaprevir and pibrentasvir for hepatitis C flare during R-CHOP in a patient with diffuse large B-cell lymphoma (DLBCL). The patient completed five additional courses of R-CHOP without hepatic toxicity. A complete response of DLBCL and a sustained virological response were observed at 24 weeks after glecaprevir and pibrentasvir completion. Conclusion On-demand, direct-acting antivirals could be a novel strategy for managing hepatitis C flare during R-CHOP.

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Association between the proliferative rate of neoplastic B cells, their maturation stage, and underlying cytogenetic abnormalities in B-cell chronic lymphoproliferative disorders: analysis of a series of 432 patients

Blood ◽

10.1182/blood-2007-10-119289 ◽

2008 ◽

Vol 111 (10) ◽

pp. 5130-5141 ◽

Cited By ~ 17

Author(s):

Sandra Quijano ◽

Antonio López ◽

Ana Rasillo ◽

Susana Barrena ◽

Maria Luz Sánchez ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoproliferative Disorders ◽

Lymphocytic Leukemia ◽

Maturation Stage ◽

Cytogenetic Abnormalities ◽

M Phase ◽

The Impact

Abstract Limited knowledge exists about the impact of specific genetic abnormalities on the proliferation of neoplastic B cells from chronic lymphoproliferative disorders (B-CLPDs). Here we analyze the impact of cytogenetic abnormalities on the proliferation of neoplastic B cells in 432 B-CLPD patients, grouped according to diagnosis and site of sampling, versus their normal counterparts. Overall, proliferation of neoplastic B cells highly varied among the different B-CLPD subtypes, the greatest numbers of proliferating cells being identified in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Compared with normal B cells, neoplastic B-CLPD cells showed significantly increased S + G2/M-phase values in mantle cell lymphoma (MCL), B-chronic lymphocytic leukemia (B-CLL), BL, and some DLBCL cases. Conversely, decreased proliferation was observed in follicular lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), and some DLBCL patients; hairy cell leukemia, splenic marginal zone, and MALT-lymphoma patients showed S + G2/M phase values similar to normal mature B lymphocytes from LN. Interestingly, in B-CLL and MCL significantly higher percentages of S + G2/M cells were detected in BM versus PB and in LN versus BM and PB samples, respectively. In turn, presence of 14q32.3 gene rearrangements and DNA aneuploidy, was associated with a higher percentage of S + G2/M-phase cells among LPL/WM and B-CLL cases, respectively.

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Clinicopathological analysis of methotrexate-associated lymphoproliferative disorders: Comparison of diffuse large B-cell lymphoma and classical Hodgkin lymphoma types

Cancer Science ◽

10.1111/cas.13249 ◽

2017 ◽

Vol 108 (6) ◽

pp. 1271-1280 ◽

Cited By ~ 33

Author(s):

Yuka Gion ◽

Noriko Iwaki ◽

Katsuyoshi Takata ◽

Mai Takeuchi ◽

Keiichiro Nishida ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoproliferative Disorders ◽

Classical Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Clinicopathological Analysis ◽

Large B Cell

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Increased Activity of Prothrombinase Fgl-2 in Peripheral Blood Mononuclear Cells of Patients with B-Cell Lymphoma.

Blood ◽

10.1182/blood.v120.21.2665.2665 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2665-2665

Author(s):

Ofir Wolach ◽

Esther Rabizadeh ◽

Doron Lederfein ◽

Natalia Binkovski ◽

Pia Raanani ◽

...

Keyword(s):

B Cell ◽

Peripheral Blood Mononuclear Cells ◽

Thrombin Generation ◽

Mononuclear Cells ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Fold Increase ◽

Lymphoproliferative Disorders ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

Abstract Abstract 2665 Background: Hematologic and solid tumors are associated with hypercoagulability the reason for which has not been delineated. Prothrombinase named fibrinogen-like protein 2 (FGL-2) is a 70 kD transmembrane protein that was found to have a quality of a serine protease capable of directly cleaving prothrombin to thrombin. FGL-2 is synthesized by monocytes, T-lymphocytes and endothelial cells. FGL-2 protein and its mRNA have been previously found within different tumor cells. Aim: To study the role of FGL-2 in patients with lymphoproliferative disorders. Our hypothesis is that upregulation of FGL-2 activity in patients with B-cell malignancies may contribute to tumorigenesis via generation of thrombin leading to increased angiogenesis and spread/metastasis of malignant cells. Methods: Thrombin generation reflecting FGL-2 activity was measured in homogenized peripheral blood mononuclear cells (PBMC) from 29 patients with active lymphoproliferative disorders and 107 normal controls. Informed consent was obtained from every participant. PBMC extracts were incubated with an equal volume of human prothrombin (final concentration10 μM) for 30 min at 37 °C. Thrombin generation was measured at 405 nm using an automated plate reader after addition of chromogen S-2238. The thrombin activity of each sample was calculated by comparison with absorbance curve generated by known concentrations of human thrombin. FGL-2 was immunoprecipitated (IP) from PBMC with an anti-FGL-2 antibody and EZview Red Protein A Affinity Gel (sigma # P6486). The activity of IP FGL-2 was measured by thrombin generation assay. The expression of FGL-2 was analyzed in HUVEC and PBMC in the presence or absence of IF-γ at 20 ng/ml. Total RNA was isolated using RNAqueous™ (Ambion #AM1912) and RT-PCR, analysis was performed using Rotor-gene RG-3000 (Corbett). The difference in cycle time (ΔCT) was measured by comparing FGL-2 gene with ABL-1 gene (house keeping gene). The relative quantification was calculated by the formula RQ= 2−ΔCT. HUVEC were transfected with 0.5 μM SiRNA synthesized complementary to FGL-2 (Target SiRNA) using Dharmacon ON-TARGET plus SMART pool reagent (Thermo Fisher Scientific) according to manufacturer instructions. FGL-2 expression following addition of target SiRNA was compared to that obtained following addition of non-specific (non-target) SiRNA. Student's t-test was used for all comparisons. Results: As shown in the table, almost 3-fold increase in FGL-2 activity in PBMC was observed among patients with active B-cell lymphoma, either aggressive or indolent, as compared to that of healthy controls (p<0.0001 for all comparisons). No difference in FGL-2 activity in PBMC between patients with aggressive and indolent lymphoma was observed (p=0.68). Three-fold increase in thrombin generation was obtained in PBMC from the patients following IP, similarly to that observed in non-IP PBMC. A significant increase in mRNA of FGL-2 was found in either PBMC of lymphoma patient or HUVEC treated with IF-γ. In HUVEC the increase in FGL-2 mRNA was inhibited by 80% following treatment with specific SiRNA. Conclusions: Disclosures: No relevant conflicts of interest to declare.

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