scholarly journals Prognostic Value of Histone Modifying Enzyme EZH2 in RCHOP-Treated Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma

2021 ◽  
Vol 11 (12) ◽  
pp. 1384
Author(s):  
Sara Petronilho ◽  
José Pedro Sequeira ◽  
Sofia Paulino ◽  
Paula Lopes ◽  
Susana Lisboa ◽  
...  

Background: DLBCL represent a heterogeneous group of aggressive diseases. High grade B-cell lymphomas (HGBCL) were recently individualized from DLBCL as a discrete diagnostic entity due to their worse prognosis. Currently, although most patients are successfully treated with RCHOP regimens, 1/3 will either not respond or ultimately relapse. Alterations in histone modifying enzymes have emerged as the most common alterations in DLBCL, but their role as prognostic biomarkers is controversial. We aimed to ascertain the prognostic value of EZH2 immunoexpression in RCHOP-treated DLBCL and HGBCL. Results: We performed a retrospective cohort study including 125 patients with RCHOP-treated DLBCL or HGBCL. EZH2 expression levels did not differ between diagnostic groups or between DLBCL-NOS molecular groups. We found no associations between EZH2 expression levels and outcome, including in the subgroup analysis (GC versus non-GC). Nonetheless, EZH2/BCL2 co-expression was significantly associated with worse outcome (event free survival and overall survival). Conclusion: Although EZH2 mutations are almost exclusively found in GC-DLBCL, we found similar EZH2 expression levels in both DLBCL-NOS molecular groups, suggesting non-mutational mechanisms of EZH2 deregulation. These findings suggest that the use of EZH2 antagonists might be extended to non-GC DLBCL patients with clinical benefit. EZH2/BCL2 co-expression was associated with a worse outcome.

2021 ◽  
pp. 1-8
Author(s):  
Sonia Gonzalez de Villambrosia ◽  
Mariana Bastos ◽  
Javier Menarguez Palanca ◽  
Jorge Gayoso Cruz ◽  
José-Tomás Navarro ◽  
...  

2018 ◽  
Vol 79 (9) ◽  
pp. 961-969
Author(s):  
Tomoki Motegi ◽  
Hirotaka Tomiyasu ◽  
Yuko Goto-Koshino ◽  
Masashi Takahashi ◽  
Saaya Hiyoshi-Kanemoto ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21123-e21123
Author(s):  
Michael Jaglal ◽  
Deniz Peker ◽  
Celeste M. Bello ◽  
Bijal D. Shah ◽  
Lubomir Sokol ◽  
...  

e21123 Background: B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL) or Burkitt like lymphoma is a high grade lymphoma that is associated with a high proliferation index and a complex karyotype mostly involving MYC and BCL-2 genes, so called “double hit” as well as BCL-6 or CYCLIND1 genes, so called “triple hit”. This high grade lymphoma shows an aggressive behavior for which the most appropriate therapeutic approach is yet to be established. Methods: This was a single center retrospective review of pts with a confirmed diagnosis of B cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL from 2006 to 2011. The definitive diagnosis in all cases was based on morphological and phenotypic features, and genetic abnormalities involving MYC, BCL-2, BCL-6, and or CYCLIND1. Clinicopathological data was extracted including age, gender, primary disease location, phenotypic subtype, genetic abnormalities by FISH, IPI scores, treatment regimens and survival data . Descriptive statistical analyses were utilized. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data were analyzed using SPSS version 20.0 statistical software. Results: 22 pts with "Double or Triple Hit" lymphomas were identified between 2006 and 2011. The age range at diagnosis was 33-87 years with median age of 66. 16 of 22 pts (73%) were ≥ 60 years old. Male to female ratio was 1.75 :1 (14:8). The median ECOG PS was 1. No pts had HIV. A majority of pts presented with extranodal disease 17 with only 5 pts presenting with nodal disease. The median survival of the entire cohort was 9 months with ranges 32 to 2 months. 16 of 22 pts (73%) are currently alive. In the cohort of pts that are currently alive, 10 was treated with RCHOP and 6 with RHyperCVAD. Pts who presented with CNS disease had a worse prognosis when compared to the entire cohort with a median overall survival of 6.5 months (p=0.016). Conclusions: RCHOP was the most utilized treatment regimen in the cohort of  alive patients. CNS disease is associated with worse prognosis in patients with "Double or Triple Hit" lymphomas.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5386-5386
Author(s):  
Yongqiang Wei ◽  
Muchen Xie ◽  
Fen Huang ◽  
Xiaolei Wei ◽  
Hui Jing ◽  
...  

Abstract Background: CD44 variants have been implicated in metastasis and as an unfavorable prognosis factor in many types of cancers. Our previous study had showed that CD44v6 expression implied a poor clinical outcome in diffuse large B cell lymphoma (DLBCL) patients treated with CHOP. However, it is remains unknown the prognostic value in DLBCL patients treated with R-CHOP due to our sample sizes. Therefore, to examine the prognostic value of CD44v6 expression in DLBCL patients, we performed this retrospective study. Methods: All 141 patients diagnosed as de novo DLBCL according to WHO classification were further confirmed. All patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The expression of CD44v6 was analyzed by immunohistochemistry (IHC). IHC was performed by an automated immunostainer complying with the instructions of the protocols. Results: Among all the 141 patients, the expression of CD44v6 was observed in 41 cases (29.1%). CD44v6 is expressed predominantly in non-germinal center type DLBCL. There was no significant difference in gender, age, B symptoms, performance status, LDH, stage and IPI score between patients with and without CD44v6 expression. Patients with CD44v6 expression showed significant inferior overall survival, but not event-free survival compared with CD44v6-negative patients. (p=0.022 and p=0.142, respectively).Multivariate analysis showed that the expression of CD44v6, independent of the international prognostic index and cell of origin, implied a poor overall survival (HR=2.223; 95% CI= 1.007-4.906, p=0.048), but not event-free survival (HR=1.457; 95% CI=0.773-2.745, p=0.245). Conclusions: These data suggest that the expression of CD44v6 implied poor outcome in DLBCL patients treated with R-CHOP. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 50 (3) ◽  
pp. 109-115
Author(s):  
Beata Grygalewicz

StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.


2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S97-S97
Author(s):  
A Herrmann ◽  
B Mai ◽  
S Elzamly ◽  
A Wahed ◽  
A Nguyen ◽  
...  

Abstract Introduction/Objective A 46-year-old female presented with severe back pain associated with progressive bilateral lower extremity weakness and paresthesia, urinary retention, and constipation. Computed tomography revealed a retroperitoneal mass encasing the right psoas muscle, obstructing the right kidney, and extending to the thoracolumbar region resulting in severe spinal compression. An epidural tumor resection was subsequently performed at an outside hospital. Methods Histological sections showed sheets of blastoid neoplastic cells with intermediate to large nuclei, irregular membranes, fine chromatin, and prominent nucleoli. Immunohistochemical stains showed that these cells were positive for CD43, CD79a (weak, focal), BCL2, C-MYC, and PAX5 (weak, focal) and negative for CD10, CD20, CD30, ALK1, BCL6, MUM1, and Tdt. The Ki-67 proliferation index was 75-80%. With this immunophenotype, this patient was diagnosed with a high grade B-cell lymphoma and transferred to our institution for further work-up. On review of the slides, further immunohistochemical testing was requested which revealed positivity for CD117 and myeloperoxidase (MPO). Results The overall morphological and immunophenotypical features are most compatible with myeloid sarcoma (MS) with aberrant expression of B-cell markers and this patient’s diagnosis was amended. Interestingly, the patient’s bone marrow examination only showed 2% myeloblasts with left shifted granulocytosis and concurrent fluorescence in situ hybridization (FISH) studies were negative. Conclusion A literature review showed that 40-50% of MS are misdiagnosed as lymphoma. MS can frequently stain with B-cell or T-cell markers, as seen in this case, which makes it challenging for an accurate diagnosis and sub- classification. In addition, our case is interesting in that there was only extramedullary presentation without bone marrow involvement. Typically, MS develops after the diagnosis of acute myeloid leukemia (AML) with an incidence of 3–5% after AML. It can also manifest de novo in healthy patients, who then go on to develop AML months to years later. Therefore, this patient will require close follow-up.


2021 ◽  
Author(s):  
Teruhito Takakuwa ◽  
Ryota Sakai ◽  
Shiro Koh ◽  
Hiroshi Okamura ◽  
Satoru Nanno ◽  
...  

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