scholarly journals Primary Mediastinal Large B-cell Lymphoma Treatment and Prevention of Anthracycline Cardiotoxicity: A Case Report

2021 ◽  
Vol 10 (1) ◽  
pp. 132-135
Author(s):  
A Ter-Grigoryan ◽  
P Ghazaryan ◽  
N Melkikyan ◽  
L Evoyan

Primary mediastinal B-cell lymphoma (PMBCL) is a relatively rare lymphoma subtype affecting mainly young adults. Its molecular signature and clinical features resemble classical Hodgkin lymphoma. The optimal chemotherapy for this lymphoma subtype has not been established. The addition of rituximab to anthracycline based chemotherapy improved response rates and survival. Many centers use R-CHOP as standard treatment, but the role of the intensified regimens and consolidation radiotherapy has to be clarified. Recent data coming from retrospective analyses and an ongoing prospective study addressing the problem of consolidation radiotherapy will help to better identify risk groups and apply risk-adapted and effective treatment strategies. The latest research has helped to understand molecular mechanisms of PMBCL pathogenesis and indicated targets of directed therapy for the future.

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-20
Author(s):  
Xiao-jie Liang ◽  
Na Yao ◽  
Dan Liu ◽  
Hai-ying Chen ◽  
Xin Xu ◽  
...  

Background: Stem and progenitor cell populations sequentially accumulate and lead to cancer through various genetic/epigenetic alterations. The stemness and its association with the tumor microenvironment (TME) have not been studied in diffuse large B-cell lymphoma (DLBCL). Methods: Molecular data from Gene Expression Omnibus of 702 DLBCL patients who received cyclophosphamide, doxorubicin, vincristine, and prednisone combined with rituximab (R-CHOP) were analyzed. A one-class logistic regression (OCLR) machine-learning algorithm was applied to obtain a stemness index (mRNAsi) for each patient and to build molecular stemness-associated genetic signature. A novel stemness molecular signature was established via artificial intelligence to evaluate therapeutic response and prognosis in DLBCL. The significance between the stemness signature and TME cell-infiltrating characteristics was dissected. Results: mRNAsi was biologically significant among DLBCL subtypes and was associated with overall survival (OS). Based on refined 12 stemness-related genes, the stemness molecular signature was able to classify DLBCL patients into high- and low-risk groups. The signature could accurately predict OS and provide a clinically-significant risk stratification in distinguishing DLBCL patients who benefitted from R-CHOP therapy from those with poor outcomes. TME analysis revealed negative correlation between DLBCL stemness origin and features of infiltrating immune cells. Two additional immunotherapy cohorts validated above discoveries in which patients with low-risk score showed significant clinical benefits from PD1/PD-L1 blockade. Conclusions: mRNAsi and stemness molecular signature as new prognostic algorithm was valuable to quantify DLBCL stemness and therapeutic resistance. Such molecular signature and stemness prediction model represent a solid foundation of biologic features for cancer stem cell therapy and immunotherapy in DLBCL. A. survival of patients with high and low mRNAsi. B. According to the stemness molecular signature, two cohorts were defined: high-risk and low-risk cohort. overall survival (OS) in 702 DLBCL patients in the training set. C. AUC for OS at 3 and 5 years in the training cohort to assess prognostic accuracy. D. Expression of 12 stemness signature genes between the germinal B cell and non-germinal B cell subtypes of the training cohort. E. Expression of 12 stemness signature genes between patients at early and advanced stages in the training cohort. F. Proportion of patients with different therapy responses in the high- and low-risk groups of the GSE31312 cohort. G. According to the stratification of the therapy responses, the survival analysis of DLBCL patients. H-I. Survival plots showing the stratification of risk model for each of the individual responses to R-CHOP. J. GSVA enrichment analysis showing the activation states of biological pathways in high- and low-risk groups. K. Abundance of TME-infiltrating cells between high- and low-risk groups. L. Component differences of immune cells between low-risk and high-risk samples analyzed by the CIBERSORT algorithm. M. Based on multivariate Cox regression analysis, riskScore, age, subtype, stage, ECOG, and extranodal sites were integrated to construct a nomogram for predicting patients' prognosis. N-O. Time-dependent receiver operating characteristic (ROC) curve to evaluate the accuracy of the OS nomogram. P-Q. Calibration curves for 3-year OS nomogram model in the training cohort (P), GSE31312 cohort (Q). R. Survival analyses for low- (172 cases) and high- (176 cases) riskScore patient groups in the anti-PD-L1 immunotherapy cohort (IMvigor210 cohort). S. Proportion of patients with different therapy responses in the high- and low-risk groups of the IMvigor210 cohort. T. Difference in riskScore among different clinical response groups in the anti-PD-L1 immunotherapy cohort. U. Kaplan-Meier survival curve according to stratification of the responses to anti-PD-L1 therapy. V. Correlation between each stemness molecular signature gene and each TME infiltration cell type using Pearson correlation analyses. W. Difference in ImmuneScore between high and low ODC1 expression groups. X. Differences in immune-activated pathways between the high and low ODC1 expression groups. Y. Survival analyses for patients with low or high ODC1 expression in the anti-PD-L1 immunotherapy cohort. Figure Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 11 (18) ◽  
pp. 2365-2380
Author(s):  
Aimen K Aljoundi ◽  
Clement Agoni ◽  
Fisayo A Olotu ◽  
Mahmoud ES Soliman

Aim: Blocking oncogenic signaling of B-cell receptor (BCR) has been explored as a viable strategy in the treatment of diffuse large B-cell lymphoma. Masitinib is shown to multitarget LYN, FYN and BLK kinases that propagate BCR signals to downstream effectors. However, the molecular mechanisms of its selectivity and pan-inhibition remain elusive. Materials & methods: This study therefore employed molecular dynamics simulations coupled with advanced post-molecular dynamics simulation techniques to unravel the structural mechanisms that inform the reported multitargeting ability of masitinib. Results: Molecular dynamics simulations revealed initial selective targeting of catalytic residues (Asp334/Glu335 – LYN; Asp130/Asp148/Glu54 – FYN; Asp89 – BLK) by masitinib, with high-affinity interactions via its piperazine ring at the entrance of the ATP-binding pockets, before systematic access into the hydrophobic deep pocket grooves. Conclusion: Identification of these ‘gatekeeper’ residues could open up a novel paradigm of structure-based design of highly selective pan-inhibitors of BCR signaling in the treatment of diffuse large B-cell lymphoma.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 98-98 ◽  
Author(s):  
Violaine Safar ◽  
Jehan Dupuis ◽  
Fabrice Jardin ◽  
Christophe Fruchart ◽  
Stéphane Bardet ◽  
...  

Abstract Abstract 98 Background: 18Fluorodeoxyglucose PET has been quickly integrated to the diagnostic and therapeutic armamentarium in diffuse large-B cell lymphoma (DLBCL). Moreover, early PET appears a promising prognostic tool for tailoring treatment strategies. We evaluated the predictive value of early PET in a large prospective cohort of patients treated with immunochemotherapy. Patients and methods: 112 previously untreated patients from three institutions were treated between January 2000 and October 2008 for DLBCL using an anthracycline-based regimen plus Rituximab. Chemotherapy was either an R-CHOP21 regimen (n=57) or a dose-dense regimen (R-ACVBP, n=31 or R-CHOP14, n= 24). PET was performed at diagnosis and after two cycles of treatment. Early PET results were interpreted visually as positive (PET2p) or negative (PET2n), as previously described1, but did not modify the scheduled therapy. Results: Median age at diagnosis was 59 years (range 20–79 years) and 67% of patients were males, 44% were over 60 years, 81% presented with an advanced Ann Arbor stage (III–IV), 29% had a poor performance status (ECOG 2-4), 36% had more than one extra-nodal site involved and LDH were elevated in 68%. The repartition on the basis of the International Prognosis Index was the following: low=5%, low-intermediate =35%, intermediate-high=37% and high risk=23%. After two cycles, 70 patients (63%) were PET2n and 42 (38%) were PET2p (38 patients in partial response and 4 with stable disease). Median follow-up was 38 months for living patients. Ten of 70 (14%) PET2n patients showed progression versus 22 of 42 (52%) PET2p patients. The estimated 5-year progression free survival (PFS) was 81% for PET2n and 47% for PET2p patients (log rank test, p<0.0001). Prognostic value of early PET was significant in terms of PFS whether patients were treated with R-CHOP21 (p=0.0006) or with dose-dense regimens (p=0.0056). Nine of 70 (13%) PET2n and 15 of 42 (36%) PET2p patients died. The estimated 5-year overall survival (OS) was 88% for PET2n and 62% for PET2p patients (log rank test, p<0.0034). Prognostic value of early PET was significant in terms of OS for patients treated with R-CHOP21 (p=0. 0225) but not for those treated with dose-dense regimens (p=0.133). Conclusion: Early PET after 2 cycles of treatment is a powerful tool to predict outcome in DLBCL patients treated with Rituximab combined with an anthracycline-based chemotherapy. It brings promising opportunities in the designing of new treatment strategies for DLBCL. Reference : 1 Haioun et al. Blood 2005; 106(4):1376–81. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2064-2064 ◽  
Author(s):  
Udomsak Bunworasate ◽  
Noppadol Siritanaratanakul ◽  
Archrop Khuhapinant ◽  
Arnuparp Lekhakula ◽  
Pairaya Rujirojindakul ◽  
...  

Abstract Abstract 2064 OBJECTIVE: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in Thailand. The objective of the study was to evaluate clinical features, histopathology, treatment outcomes and prognostic factors in Thai adult patients with NHL. METHODS: Using web-based registry system, we prospectively collected clinical information of newly diagnosed NHL patients from eleven major medical centers situated in various geographic regions of Thailand. All histopathological diagnoses were reviewed by consensus meeting of panels of 6 expert hematopathologists and classified according to the 2008 WHO classification of the lymphoid neoplasms. Clinical features and treatment outcomes were analyzed using STATA program. RESULTS: Between January 2007 and May 2009, there were a total of 939 NHL patients whose clinical information including follow-up data and tissue samples were readily available for analysis. The median age was 58 years (range, 15–99). Forty six percent of the patients were ≥60 years of age. Male:female was 1.18:1. The six leading subtypes were diffuse large B-cell lymphoma (67%), extranodal marginal zone lymphoma of MALT type (7%), follicular lymphoma (6%), mantle cell lymphoma (4%), peripheral T-cell lymphoma, not otherwise specified (NOS) (3%) and extranodal NK/T-cell lymphoma, nasal type (3%). T-cell lymphoma constituted 10% of all NHL. The three most common subtypes in T-cell lymphomas were peripheral T-cell lymphoma, NOS (26%), extranodal NK/T-cell lymphoma, nasal type (25%) and angioimmunoblastic T-cell lymphoma (15%). Fifty-eight percent of all patients had advanced disease (stage III, IV), 42% had B symptoms and 54% had elevated serum LDH. The IPI risk groups were 23% low, 30% low-intermediate, 30% high-intermediate and 17% high-risk. HIV-associated NHL was seen in 4.4% of the patients. Of the 801 patients who received chemotherapy, 90% were treated with anthracycline-containing regimen. Twenty-five percent of the patients received rituximab. Of the 663 evaluable patients, the rate of objective tumor response was 75% (CR+CRu, 59%). At a median follow-up time of 13 months, the 4-year projected overall survival (OS) was 73% (95% CI 69–77%). The OS of patients with T-cell lymphoma was inferior to B-cell lymphoma (58% vs. 74%, p = 0.04). With multivariate analysis, the independent adverse prognostic factors for OS in B-cell lymphoma were poor performance status (HR 2.4, 95% CI 1.7–3.5), elevated serum LDH (HR 2.1, 95% CI 1.4–3.1), stage III/IV (HR 1.6, 95% CI 1.1–2.3), WHO subtype (HR 1.1, 95% CI 1.0–1.2), no chemotherapy (HR 3.1, 95% CI 1.9–5.1) and no rituximab treatment (HR 1.7, 95% CI 1.1–2.6). The independent adverse factors for OS in T-cell lymphoma were elevated serum LDH (HR 3.7, 95% CI 1.2–11.1) and male sex (HR 3.4, 95% CI 1.3–8.8). CONCLUSIONS: This study confirmed the characteristic features of NHL among Thai population, i.e., a preponderance of diffuse large B-cell lymphoma and a low incidence of follicular lymphoma within B-cell lymphoma; a relatively high incidence of nasal NK/T-cell lymphoma within T-cell lymphoma. The IPI risk-groups and survival outcomes were comparable to most previously published reports. Disclosures: Bunworasate: Novartis Pharmaceutical: Research Funding. Off Label Use: Nilotinib is a safe and effective treatment for patients with CML. Chuncharunee:Novartis: Research Funding.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8570-8570
Author(s):  
C. Yoo ◽  
B. Sohn ◽  
J. Kim ◽  
D. Yoon ◽  
J. Huh ◽  
...  

8570 Background: The combination of rituximab and CHOP chemotherapy (R-CHOP) has improved survival of patients with diffuse large B-cell lymphoma (DLBCL). Recently, several reports have shown that standard International Prognostic Index (IPI) became less powerful prognostic predictor in patients with DLBCL in the era of R-CHOP. We evaluated the prognostic factors of DLBCL patients treated with R-CHOP. Detailed analysis was planned regarding the number of extranodal sites because of its higher frequency in Korea. Methods: Between January 2002 and May 2008, 126 patients with stage III/IV DLBCL treated with R-CHOP were identified. We performed the retrospective analysis of the clinicopathologic factors and verified the predictive power of standard IPI and revised IPI (R-IPI) which was reported by the study group of British Columbia. Various numbers of extranodal sites were analyzed for further stratification and we set E-IPI as the IPI when the number of extranodal sites is stratified in ≤2 vs >2. Results: In the univariate analysis, the number of extranodal sites (≤2 vs >2) was a significant prognostic factor for complete response (CR) (p=0.04), event-free survival (EFS) (p=0.01) and overall survival (OS) (p<0.001). Age was also significant for EFS (p=0.03). When the number of extranodal site was stratified differently (0 vs >0, or ≤1 vs >1), these were not associated with CR, EFS and OS. On the multivariate analysis, the number of extranodal sites (≤2 vs >2) remained significant for EFS (p<0.01, HR 2.6) and OS (p<0.01, HR 3.5). The standard IPI identified 3 risk groups with 2-year EFS; 68%, 55%, 56% (p=0.17) and 2-year OS; 85%, 68%, 58%, respectively (p=0.04). The R-IPI classified 2 risk groups with 2-year EFS; 65%, 50% (p=0.02) and 2-year OS 76%, 62%, respectively (p=0.04). The E-IPI represented 3 risk groups with 2-year EFS; 79%, 56%, 42% (p=0.01) and 2-year OS; 86%, 70%, 39%, respectively (p=0.001). The patient group with survival of less than 50% was only recognized by E-IPI. Conclusions: The number of extranodal sites (≤2 vs >2) is the most significant prognostic factor of EFS and OS. Although all three indices remain predictive, E-IPI is the best model to identify the prognostic group in this cohort with stage III/IV DLBCL treated with R-CHOP. No significant financial relationships to disclose.


2012 ◽  
Vol 97 (1) ◽  
pp. 98-102 ◽  
Author(s):  
Rika Kihara ◽  
Tomoyuki Watanabe ◽  
Takahiro Yano ◽  
Naokuni Uike ◽  
Seiichi Okamura ◽  
...  

2003 ◽  
Vol 15 (2) ◽  
pp. 1-5 ◽  
Author(s):  
James K. Liu ◽  
Peter Kan ◽  
Meic H. Schmidt

Primary lymphomas of the sacrum are rare tumors, reported only in a few cases in the literature. The authors describe two patients with diffuse large B-cell lymphomas presenting as a sacral tumor. In the first case a 52-year-old man presented with progressive back pain, bilateral radicular pain, and saddle block anesthesia secondary to a lytic, expansile soft-tissue mass. The mass arose from the sacrum and eroded through the right S-1 to S-4 foramina and extended into the epidural space of the spinal canal. On magnetic resonance imaging, the sacral mass enhanced homogeneously with Gd. In the second case a 64-year-old man presented with left-sided radicular pain, paresthesias, and progressive weakness due to a lytic soft-tissue mass in the left sacral ala extending into the left L-5 and S-1 foramina. Metastatic workup in each patient demonstrated unremarkable findings. In both cases, an open biopsy procedure was performed after nondiagnostic examination of needle biopsy samples. Histopathological examination showed evidence consistent with diffuse large B-cell lymphoma in both patients. In the first case the disease was classified as Stage IAE, and the patient subsequently underwent four cycles of cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP)– and rituximab-based chemotherapy followed by consolidation radiotherapy. In the second case the disease was also classified as Stage IAE, and the patient underwent CHOP-based chemotherapy and consolidation radiotherapy. In both cases radiography demonstrated a decrease in size of the sacral lymphomas. The authors review the clinical, radiological, and histological features of sacral lymphomas. Lymphoma should be considered in the differential diagnosis of sacral tumors.


2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Kong Linling ◽  
Zou Lingqing ◽  
Gu Siyu ◽  
Liu Hong ◽  
Song Guoqi ◽  
...  

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