Clinical characteristics and molecular heterogeneity in Follicular lymphoma with extranodal involvement

BackgroundDiffuse large B‐cell lymphoma (DLBCL) is an aggressive subtype of lymphoma, and multiple extranodal involvement (ENI) indicates adverse clinical outcomes. The aim of this study was to investigate the influence of oncogenic mutations and tumor microenvironment alterations on ENI in DLBCL.MethodsThe clinical features of 1960 patients with newly diagnosed DLBCL were analyzed, and DNA and RNA sequencing was performed on 670 and 349 patients, respectively. Oncogenic mutations and tumor microenvironment alterations were compared according to ENI and evaluated in zebrafish patient‐derived tumor xenograft models.ResultsMultiple ENI was significantly associated with poor performance status, advanced stage, elevated serum lactate dehydrogenase, low response rate, and inferior prognosis. Lymphoma invasion of the bones, spleen, bone marrow, liver, and central nervous system were independent unfavorable prognostic factors. MYD88 was frequently mutated in patients with multiple ENI, co‐occurred with mutations in CD79B, PIM1, TBL1XR1, BTG1, MPEG1, and PRDM1, and correlated with invasion of the bones, kidney/adrenal glands, breasts, testes, skin, and uterus/ovaries. For tumor microenvironment alterations, patients with multiple ENI showed higher regulatory T‐cell (Treg)‐recruiting activity, but lower extracellular matrix‐encoding gene expression, than those without ENI and with single ENI. Elevated Treg‐recruiting activity was related to mutations in B2M, SGK1, FOXO1, HIST1H1E, and ARID1A, and correlated with invasion of the bone marrow and thyroid. Additionally, mutations in MYD88, PIM1, TBL1XR1, SGK1, FOXO1, HIST1H1E, and ARID1A were associated with decreased major histocompatibility complex class I expression. Zebrafish models further revealed relationships between MYD88 mutations and invasion of the kidneys and gonads, as well as B2M mutations and invasion of the bone marrow. Increased CXCR4 expression is linked to bone marrow invasion in an organotropic way.ConclusionsOur findings thus contribute to an improved understanding of the biological behavior of multiple ENI and provide a clinical rationale for targeting ENI in DLBCL.

Exploration of Rituximab Plus Lenalidomide（R2）in Newly Diagnosed Diffuse Large B Cell Lymphoma with Adverse Prognostic Factors As Maintenance Therapy

Autologous Stem Cell Transplant in Fit Patients with Late Relapsed Diffuse Large B-Cell Lymphoma That Responded to Salvage Chemotherapy

Outcome of T-Cell/Histiocyte-Rich Large B-Cell Lymphoma in Denmark 2008-2022

Primary Bone Non-Hodgkin's Lymphoma: A Specific Clinical Entity with Aggressive Clinical Course and High Cure Rate - Retrospective Analysis of 102 Patients from Greece

A New Simplified Prognostic Index Integrating the Type of Extra-Nodal Involvement and Age for Ann Arbor Stage IV Hodgkin Lymphoma Patients Diagnosed at TEP-Scanner Era: A Retrospective Analysis from Lymphoma Study Association (LYSA) Centers

Prognostic Utility of Extranodal Disease Involvement in Diffuse Large B-Cell Lymphoma in Patients Treated with R-CHOP.

目的评估RCDOP（利妥昔单抗、环磷酰胺、脂质体多柔比星、长春新碱、泼尼松）方案在弥漫大B细胞淋巴瘤（DLBCL）患者中的疗效。方法回顾性分析2012年10月至2017年10月应用RCDOP方案治疗的87例初治DLBCL患者资料，结合临床特征进行疗效和生存分析。结果①87例患者中，男40例，女47例，中位年龄60（14~84）岁。应用RCDOP方案治疗后，获得完全缓解（CR）和部分缓解（PR）者共计81例（93.10%）。②根据IPI评分不同危险度分层（低、中、高危）、结外累及部位（0~1个/≥2个）、肿块大小（<7.5 cm≥7.5 cm）、年龄（≤60岁/>60岁）、LDH（正常/升高）、Ann Arbor分期（Ⅰ~Ⅱ期/Ⅲ~Ⅳ期）、Ki-67阳性率（>80%/≤80%）对患者进行分组，比较组间无进展生存（PFS）和总生存（OS）的差异。结果显示，RCDOP方案治疗后，中位随访时间为9个月，IPI评分低、中、高危三组患者的1年PFS率（P=0.084）和OS率（P=0.515）差异无统计学意义，其余组间比较患者的1年PFS率和OS率差异也均无统计学意义（P值均>0.05）。结论RCDOP方案可以改善IPI评分中高危、结外多部位累及、巨大肿块、年龄>60岁、高LDH、Ann Arbor分期Ⅲ~Ⅳ期和Ki-67阳性率>80%患者的早期疗效。

Prognostic Implication Of Circulating Vascular Endothelial Growth Factor In Patients With Diffuse Large B-Cell Lymphoma

Treatment Outcomes of Zanubrutinib-Based Regimen in Newly Diagnosed Patients with MYC/BCL2 Double-Expressor Diffuse Large B-Cell Lymphoma: A Retrospective Multicenter Real-World Study

A Matched Comparison of Pola-R-CHP Vs. R-CHOP for DLBCL with Extranodal Involvement

Outcome of Extra-Nodal Follicular Lymphoma Affected By Selection of Induction Chemoimmunotherapy and Maintenance Rituximab - Real-World Retrospective Study

CNS Relapse in Diffuse Large B-Cell Lymphoma Patients with Oral Cavity and Bone Marrow Involvement-Experience from an Inner City Hospital

Background: Follicular lymphoma (FL), an indolent non-Hodgkin lymphoma (NHL), is generally incurable. Favourable prognosis and durable remission are crucial for FL patients. The genetic mutation spectrum provides novel biomarkers for determining the prognosis of FL patients, but its detection is easily affected by the collection of tumour tissue biopsies. In this study, we aimed to describe the mutational landscape of FL using circulating tumour DNA (ctDNA) samples and to explore the relationship between mutations and prognostic indicators of clinical outcome in patients with newly diagnosed follicular lymphoma and the prognostic value of such mutations.Methods: A total of 28 patients with newly diagnosed FL were included in this study. A targeted NGS-based 59-gene panel was used to assess the ctDNA mutation profiles. Differences in clinical factors between patients carrying mutations and those without mutations were analysed. We also explored the relationship between gene mutation status, mean VAFs (variant allele frequencies) and clinical factors. The Kaplan‒Meier method was applied to analyse the overall survival (OS) and progression-free survival (PFS) of patients carrying mutations and those without mutations.Results: ctDNA mutations were detectable in 21 (75%) patients. The most commonly mutated genes were CREBBP (54%, 15/28), KMT2D (50%, 14/28), STAT6 (29%, 8/28), CARD11 (18%, 5/28), PCLO (14%, 4/28), EP300 (14%, 4/28), BCL2 (11%, 3/28), and TNFAIP3 (11%, 3/28), with a mutation frequency of >10%. Patients with detectable ctDNA mutation tended to present with advanced Ann Arbor stage (III-IV) (p = 0.009), high FLIPI risk (3–5) (p = 0.023) and severe lymph node involvement (No. of involved areas ≥5) (p = 0.02). In addition, we found that the mean VAF was significantly higher in patients with advanced Ann Arbor stage, high-risk FLIPI, elevated lactate dehydrogenase (LDH: 0–248U/L), advanced pathology grade, bone marrow involvement (BMI) and lymph node involvement. Additionally, KMT2D, EP300, and STAT6 mutations were associated with inferior PFS (p < 0.05).Conclusion: We described the ctDNA mutation landscapes in Chinese patients with newly diagnosed FL and found that ctDNA VAF means reflect tumour burden. Moreover, PFS was shorter in patients with KMT2D, EP300 and STAT6 mutations.

Impact of MYC Alterations in De Novo and Transformed Large B-Cell Lymphoma: An Italian Single Center Experience