An analysis of MYC and EBV in diffuse large B-cell lymphomas associated with angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified

Hoffmann, Jenny C.; Chisholm, Karen M.; Cherry, Athena M.; Chen, Jennifer; Arber, Daniel A.; Natkunam, Yasodha; Warnke, Roger A.; Ohgami, Robert S.

doi:10.1016/j.humpath.2015.09.033

Cited by 25 publications

(25 citation statements)

References 25 publications

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“…In this study, we also describe the largest clinically annotated series of EBV + DLBCL (NOS) with subsequent and/or composite peripheral T cell lymphoma to date. Despite a promising ORR upon first‐line therapy, more than half of the patients in our cohort experienced relapse with a high degree of secondary resistance towards immunochemotherapy, which closely resembles the overall poor outcome described in case reports and smaller case studies so far (Xu et al , ; Zettl et al , ; Hoffmann et al , ). As previously described, we found that several cases of EBV + DLBCL (NOS) emerged from an underlying peripheral T cell lymphoma (AITL) (Hoffmann et al , ).…”

Section: Discussionsupporting

confidence: 77%

“…Despite a promising ORR upon first‐line therapy, more than half of the patients in our cohort experienced relapse with a high degree of secondary resistance towards immunochemotherapy, which closely resembles the overall poor outcome described in case reports and smaller case studies so far (Xu et al , ; Zettl et al , ; Hoffmann et al , ). As previously described, we found that several cases of EBV + DLBCL (NOS) emerged from an underlying peripheral T cell lymphoma (AITL) (Hoffmann et al , ). We additionally found five of the above‐mentioned cases to be of particular interest, as EBV + DLBCL (NOS) with demonstrated clonal intra‐tumour T cell populations in 4/5 cases preceded clonally‐related peripheral T cell lymphoma by 7–40 months.…”

Section: Discussionsupporting

confidence: 77%

“…Several minor case studies found these clonal T cell infiltrates to constitute associated or composite (and almost exclusively) peripheral T cell lymphomas [predominantly angioimmunoblastic T cell lymphoma, followed by peripheral T cell lymphoma (NOS)], for which a pathogenetic conjunction with EBV + DLBCL (NOS) is still to be elucidated. A widely accepted hypothesis states that the immunosuppressive nature of T cell lymphomas may pose an immunological niche in which the proliferation and subsequent immortalisation of EBV‐infected bystander B cells is facilitated (Hoffmann et al , ).…”

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confidence: 99%

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Impact of treatment variability and clinicopathological characteristics on survival in patients with Epstein‐Barr‐Virus positive diffuse large B cell lymphoma

Witte

Merz²,

Biersack

et al. 2020

Br J Haematol

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Patients with EBV-positive diffuse large B cell lymphoma not otherwise specified (EBV + DLBCL (NOS)) recurrently present with advanced age and reduced performance status. They are therefore insufficiently represented in clinical trials and treatment is likely to differ. Here we assess clinicopathological characteristics, therapeutic variability and clinical outcome in the largest consecutively diagnosed EBV + DLBCL (NOS) cohort published to date (n = 80; median age 70 years; range 19-90). Centralized and systematic haematopathological panel review was performed. By immunohistochemistry 60/80 patients were CD30-positive. Further, we identified nine EBV + DLBCL (NOS) patients with associated or composite peripheral T cell lymphoma at diagnosis or relapse (preceded by clonal T cell populations within the initial DLBCL biopsy in 4/5 cases). Most patients (80%) were treated with R-CHOP-type therapy and 16 patients received none or less intensiveprotocols. Upon univariate analysis both R-CHOP-type therapy (OS: P < 0.0001; PFS: P = 0.0617) and negativity for CD30 (OS: P = 0.0002; PFS: P = 0.0002) showed a protective 66 effect, maintained upon multivariate analysis. In a propensity-score matched analysis with a cohort of non-EBV + DLBCL (NOS) patients, balanced for all revisedinternational prognostic index factors, we found an EBV-association to hold no significant impact on progression-free and overall survival whilst exhibiting a trend favouring EBV-negativity (OS: P = 0.116; PFS: P = 0.269). Our findings provide insight into the clinical course of EBV + DLBCL (NOS), highlight the ramifications of CD30-expression and underline the superior therapeutic efficacy of R-CHOP immunochemotherapy. Alternative therapies, incorporating tumour biology (e.g. CD30 directed therapies) need to be explored in EBV + DLBCL (NOS) patients. Moreover our data advert to the close relationship between EBV + DLBCL (NOS) and peripheral T cell lymphomas.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

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Impact of treatment variability and clinicopathological characteristics on survival in patients with Epstein‐Barr‐Virus positive diffuse large B cell lymphoma

Witte

Merz²,

Biersack

et al. 2020

Br J Haematol

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“…AITL demonstrates a T follicular helper cell (T FH ) phenotype and typically is associated with B cells infected by EBV; the neoplastic T cells are EBV-negative. Some patients also develop diffuse large B cell lymphoma, which often is EBV-positive [13]. …”

Section: Angioimmunoblastic T Cell Lymphomamentioning

confidence: 99%

Genetic Landscape and Classification of Peripheral T Cell Lymphomas

2017

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Purpose of review Peripheral T cell lymphomas (PTCLs) are markedly heterogeneous at the clinical, pathological, and molecular levels. This review will discuss genetic findings in PTCL with special emphasis on how they impact lymphoma classification. Recent findings Sequencing studies have identified recurrent genetic alterations in nearly every PTCL subtype. In anaplastic large cell lymphoma, these studies have revealed novel chromosomal rearrangements and mutations that have prognostic significance and may suggest new therapeutic approaches. Angioimmunoblastic T cell lymphoma has been found to have mutations overlapping some cases of PTCL, not otherwise specified with a T follicular helper cell phenotype. Across various subtypes, recurrent mutations and structural alterations affecting genes involved in epigenetic regulation, T cell receptor signaling, and immune response may represent targets for precision therapy approaches. Summary New genetic findings are refining the classification of PTCLs and are beginning to be used clinically for diagnosis, risk stratification, and individualized therapy.

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“…These secondary malignancies commonly present as either composite lymphomas of diffuse large B-cell lymphoma + AITL (73, 74) or polyclonal populations of immunoblasts or plasma cells (75, 76). The development of these secondary malignancies suggests that the malignant T cells still hold the effector capacity to stimulate B-cell proliferation and antibody production and indicate a relationship between the developments of the two separate disease phenotypes (77, 78).…”

Section: Angioimmunoblastic T-cell Lymphomamentioning

confidence: 99%

Using Murine Models to Investigate Tumor–Lymphoid Interactions: Spotlight on Chronic Lymphocytic Leukemia and Angioimmunoblastic T-Cell Lymphoma

Herek

Cutucache

2017

Front. Oncol.

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The role of the tumor microenvironment in leukemias and lymphomas is well established, yet the intricacies of how the malignant cells regulate and influence their non-malignant counterparts remain elusive. For example, chronic lymphocytic leukemia (CLL) is an expansion of malignant CD5+CD19+ B cells, yet the non-malignant T cells play just as large of a role in disease presentation and etiology. Herein, we review the dynamic tumor cell to lymphoid repertoire interactions found in two non-Hodgkin’s lymphoma subtypes: CLL and angioimmunoblastic T-cell lymphoma. We aim to highlight the pivot work done in the murine models which recapitulate these diseases and explore the insights that can be gained from studying the immuno-oncological regulation of non-malignant lymphoid counterparts.

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An analysis of MYC and EBV in diffuse large B-cell lymphomas associated with angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified

Cited by 25 publications

References 25 publications

Impact of treatment variability and clinicopathological characteristics on survival in patients with Epstein‐Barr‐Virus positive diffuse large B cell lymphoma

Impact of treatment variability and clinicopathological characteristics on survival in patients with Epstein‐Barr‐Virus positive diffuse large B cell lymphoma

Genetic Landscape and Classification of Peripheral T Cell Lymphomas

Using Murine Models to Investigate Tumor–Lymphoid Interactions: Spotlight on Chronic Lymphocytic Leukemia and Angioimmunoblastic T-Cell Lymphoma

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