Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission.

In patients with relapsed DLBCL in complete remission (CR), autologous hematopoietic cell transplantation (auto-HCT) and CAR-T therapy are both effective, but it is unknown which modality provides superior outcomes. We compared the efficacy of auto-HCT vs. CAR-T in patients with DLBCL in a CR. A retrospective observational study comparing auto-HCT (2015-2021) vs. CAR-T (2018-2021) using the Center for International Blood & Marrow Transplant Research registry. Median follow-up was 49.7 months for the auto-HCT and 24.7 months for the CAR-T cohort. Patients ages 18 and 75 with a diagnosis of DLBCL were included if they received auto-HCT (n = 281) or commercial CAR-T (n = 79) while in a CR. Patients undergoing auto-HCT with only one prior therapy line and CAR-T patients with a previous history of auto-HCT treatment were excluded. Endpoints included Progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS). In univariate analysis, treatment with auto-HCT was associated with a higher rate of 2-year PFS (66.2% vs. 47.8%; p < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs. 48% ; p < 0.001), and a superior 2-year OS (78.9% vs. 65.6%; p = 0.037). In patients with early (within 12 months) treatment failure, auto-HCT was associated with a superior 2-year PFS (70.9% vs. 48.3% ; p < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs. 45.9% ; p < 0.001) and trend for higher 2-year OS (82.4% vs. 66.1% ; p = 0.076). In the multivariable analysis, treatment with auto-HCT was associated with a superior PFS (hazard ratio 1.83; p = 0.0011) and lower incidence of relapse (hazard ratio 2.18; p < 0.0001) compared to CAR-T. In patients with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with improved clinical outcomes compared to CAR-T. These data support the consideration of auto-HCT in select patients with LBCL achieving a CR in the relapsed setting.

Tumor purity-related genes for predicting the prognosis and drug sensitivity of DLBCL patients.

Background: Diffuse large B-cell lymphoma (DLBCL) is the predominant type of malignant B-cell lymphoma. Although various treatments have been developed, the limited efficacy calls for more and further exploration of its characteristics. Methods: Datasets from the Gene Expression Omnibus (GEO) database were used for identifying the tumor purity of DLBCL. Survival analysis was employed for analyzing the prognosis of DLBCL patients. Immunohistochemistry was conducted to detect the important factors that influenced the prognosis. Drug-sensitive prediction was performed to evaluate the value of the model. Results: VCAN, CD3G, and C1QB were identified as three key genes that impacted the outcome of DLBCL patients both in GEO datasets and samples from our center. Among them, VCAN and CD3G+ T cells were correlated with favorable prognosis, and C1QB was correlated with worse prognosis. The ratio of CD68 + macrophages and CD8 + T cells was associated with better prognosis. In addition, CD3G+T cells ratio was significantly correlated with CD68 + macrophages, CD4 + T cells, and CD8 +T cells ratio, indicating it could play an important role in the anti-tumor immunity in DLBCL. The riskScore model constructed based on the RNASeq data of VCAN, C1QB, and CD3G work well in predicting the prognosis and drug sensitivity. Conclusions: VCAN, CD3G, and C1QB were three key genes that influenced the tumor purity of DLBCL, and could also exert certain impact on drug sensitivity and prognosis of DLBCL patients. Funding: This work is supported by the Shenzhen High-level Hospital Construction Fund and CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-062).

[Clinicopathologic characteristics and survival analysis of primary large B-cell lymphoma of the central nervous system].

Objective: To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) . Methods: Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model. Results: Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy (P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months (P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL (HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions: In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

Patient-specific computational models predict prognosis in B cell lymphoma by quantifying pro-proliferative and anti-apoptotic signatures from genetic sequencing data.

Genetic heterogeneity and co-occurring driver mutations impact clinical outcomes in blood cancers, but predicting the emergent effect of co-occurring mutations that impact multiple complex and interacting signalling networks is challenging. Here, we used mathematical models to predict the impact of co-occurring mutations on cellular signalling and cell fates in diffuse large B cell lymphoma and multiple myeloma. Simulations predicted adverse impact on clinical prognosis when combinations of mutations induced both anti-apoptotic (AA) and pro-proliferative (PP) signalling. We integrated patient-specific mutational profiles into personalised lymphoma models, and identified patients characterised by simultaneous upregulation of anti-apoptotic and pro-proliferative (AAPP) signalling in all genomic and cell-of-origin classifications (8-25% of patients). In a discovery cohort and two validation cohorts, patients with upregulation of neither, one (AA or PP), or both (AAPP) signalling states had good, intermediate and poor prognosis respectively. Combining AAPP signalling with genetic or clinical prognostic predictors reliably stratified patients into striking prognostic categories. AAPP patients in poor prognosis genetic clusters had 7.8 months median overall survival, while patients lacking both features had 90% overall survival at 120 months in a validation cohort. Personalised computational models enable identification of novel risk-stratified patient subgroups, providing a valuable tool for future risk-adapted clinical trials.

Hematopoietic stem cell transplantation for DLBCL: a report from the European Society for Blood and Marrow Transplantation on more than 40,000 patients over 32 years.

Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990-1994) to 58 years (2015-2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990-1994) to 54 (2015-2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015-2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990-1994) to 70% (2015-2021), p < 0.001, with a decrease in relapse incidence (RI) from 49% to 38%, while non-relapse mortality (NRM) remained unchanged (4%). After allo-HSCT, 3-year-OS increased from 33% (1990-1999) to 46% (2015-2021) (p < 0.001); 3-year RI remained at 39% and 1-year-NRM decreased to 19% (p < 0.001). Our data reflect advancements over 32 years and >40,000 transplants, providing insights for evaluating emerging DLBCL therapies.

Comparative Study on the Clinicopathologic and Molecular Characteristics of Primary and Secondary Diffuse Large B-cell Lymphoma in the Central Nervous System.

BACKGROUND/AIM: Diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive B-cell lymphoma with clinical and molecular heterogeneity. Primary CNS-DLBCL (PCNSL) affects the brain, eyes, leptomeninges, or spinal cord without systemic involvement. Secondary CNS-DLBCL (SCNSL) manifests concurrently with systemic lymphoma or as an isolated CNS relapse with poor prognosis. MATERIALS AND METHODS: Next-generation sequencing (NGS) was used to identify genomic alterations in 32 PCNSL and 9 SCNSL cases. Single nucleotide variants and copy number variations in addition to the clinicopathologic data and proposed risk predictive values were compared to aid in diagnostic differentiation between the two types of lymphomas. RESULTS: The MCD genotype, characterized by mutations in MYD88 and CD79B, is the most common alteration in PCNSL and is associated with lower survival rates. The frequency of MYD88 mutation was significantly higher in PCNSL compared to SCNSL (75.0% vs. 33.3%; p=0.042). Recurrent copy number loss of 6p21 occurred in 56.1% of cases, more often in PCNSL (65.6%) than in SCNSL (22.2%) (p=0.028). Diagnostic positive predictive values (PPV) of MYD88 mutation and 6p21 loss for PCNSL were 89% and 91%, respectively. PPV of both alterations was 93% for the diagnosis of PCNSL. CONCLUSION: MYD88 mutation and 6p21 loss were significantly higher in PCNSL than in SCNSL, and novel risk prediction models based on these distinct genomic profiles can aid in the clinical differentiation of PCNSL and SCNSL.

Early failure is still a poor prognostic factor in patients with relapsed or refractory large B-cell lymphoma in the era of CAR T-cell therapy.

Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.

Revisiting beta-2 microglobulin as a prognostic marker in diffuse large B-cell lymphoma.

BACKGROUND: Several clinical prognostic models for diffuse large B-cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN-IPI), and models incorporating beta-2 microglobulin (ß2M). However, the role of ß2M in DLBCL patients is not fully understood. METHODS: We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry. RESULTS: A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with ß2M and NCCN-IPI performed better than the International Prognostic Indexes (IPI, age-adjusted IPI, and revised IPI). Five-year overall survival for high- and low-risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN-IPI. In univariate analysis, higher levels of ß2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (ß2M-NCCN-IPI) by adding ß2M to NCCN-IPI (c-index 0.708) with improved discriminatory ability compared to NCCN-IPI (c-index 0.698, p < 0.05) and 5-year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high-intermediate, low-intermediate and low-risk group, respectively. CONCLUSION: International Prognostic Indices, except for NCCN-IPI, fail to accurately discriminate risk groups in the rituximab era. ß2M, a readily available marker, could improve the discriminatory performance of NCCN-IPI and should be re-evaluated in the development setting of future models for DLBCL.

Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma.

BACKGROUND: The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown. METHODS: We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs. A phase 2 expansion in patients with germinal-center B-cell (GCB) and non-GCB DLBCL was performed. ViPOR was administered every 21 days for six cycles. RESULTS: In phase 1b of the study, involving 20 patients (10 with DLBCL), a single dose-limiting toxic effect of grade 3 intracranial hemorrhage occurred, a result that established venetoclax at a dose of 800 mg as the recommended phase 2 dose. Phase 2 included 40 patients with DLBCL. Toxic effects that were observed among all the patients included grade 3 or 4 neutropenia (in 24% of the cycles), thrombocytopenia (in 23%), anemia (in 7%), and febrile neutropenia (in 1%). Objective responses occurred in 54% of 48 evaluable patients with DLBCL, and complete responses occurred in 38%; complete responses were exclusively in patients with non-GCB DLBCL and high-grade B-cell lymphoma with rearrangements of MYC and BCL2 or BCL6 (or both). Circulating tumor DNA was undetectable in 33% of the patients at the end of ViPOR therapy. With a median follow-up of 40 months, 2-year progression-free survival and overall survival were 34% (95% confidence interval [CI], 21 to 47) and 36% (95% CI, 23 to 49), respectively. CONCLUSIONS: Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated with mainly reversible adverse events. (Funded by the Intramural Research Program of the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health and others; ClinicalTrials.gov number, NCT03223610.).

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Primary colon lymphomas: An analysis of our experience over the last 18 years.

Colon lymphoma is a rare type of gastrointestinal lymphoma and represents 0.2% to -1.2% of all primary colon cancers. This study aimed to retrospectively examine the general characteristics, treatment methods, and survival characteristics of patients with colon lymphoma who were followed-up at our center. This retrospective study included patients diagnosed with colon lymphoma who were followed up at Ankara Numune Training and Research Hospital and Ankara Bilkent City Hospital between December 2005 and June 2023. Clinicopathological features, radiological findings, treatments, and modalities of patients were obtained from their medical records. Fourteen patients with primary colon lymphoma were included in the study. Thirteen patients (92.9%) were diagnosed with diffuse large B-cell lymphoma. The median age of the patients was 55 (28-84) years. The tumor location was the terminal ileum/cecum in 50% of the patients. At the time of diagnosis, 10 patients (7 with stage 1E-2E disease, 2 with stage 3E disease, and 1 with stage 4E disease due to tumor obstruction) underwent surgery. Twelve patients received chemotherapy (6 patients as adjuvant and 6 patients as first-line treatment). The median overall survival (OS) was 10 years (0.1-21.5) years, the 5-year median OS was 71%, and the 10-year median OS was 53%. Primary colon lymphoma is a rare disease and its optimal treatment is not clearly defined. The primary treatment for primary colon lymphoma is a combination of surgery and chemotherapy. A clear consensus on the treatment can be established through prospective studies.

Artificial intelligence-based prognostic model accurately predicts the survival of patients with diffuse large B-cell lymphomas: analysis of a large cohort in China.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) display high molecular heterogeneity, but the International Prognostic Index (IPI) considers only clinical indicators and has not been updated to include molecular data. Therefore, we developed a widely applicable novel scoring system with molecular indicators screened by artificial intelligence (AI) that achieves accurate prognostic stratification and promotes individualized treatments. METHODS: We retrospectively enrolled a cohort of 401 patients with DLBCL from our hospital, covering the period from January 2015 to January 2019. We included 22 variables in our analysis and assigned them weights using the random survival forest method to establish a new predictive model combining bidirectional long-short term memory (Bi-LSTM) and logistic hazard techniques. We compared the predictive performance of our "molecular-contained prognostic model" (McPM) and the IPI. In addition, we developed a simplified version of the McPM (sMcPM) to enhance its practical applicability in clinical settings. We also demonstrated the improved risk stratification capabilities of the sMcPM. RESULTS: Our McPM showed superior predictive accuracy, as indicated by its high C-index and low integrated Brier score (IBS), for both overall survival (OS) and progression-free survival (PFS). The overall performance of the McPM was also better than that of the IPI based on receiver operating characteristic (ROC) curve fitting. We selected five key indicators, including extranodal involvement sites, lactate dehydrogenase (LDH), MYC gene status, absolute monocyte count (AMC), and platelet count (PLT) to establish the sMcPM, which is more suitable for clinical applications. The sMcPM showed similar OS results (P < 0.0001 for both) to the IPI and significantly better PFS stratification results (P < 0.0001 for sMcPM vs. P = 0.44 for IPI). CONCLUSIONS: Our new McPM, including both clinical and molecular variables, showed superior overall stratification performance to the IPI, rendering it more suitable for the molecular era. Moreover, our sMcPM may become a widely used and effective stratification tool to guide individual precision treatments and drive new drug development.

Metabolic pathway-based subtyping reveals distinct microenvironmental states associated with diffuse large B-cell lymphoma outcomes.

Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. Assigning patients to different risk categories and cytogenetic abnormality and genetic mutation groups has been widely applied for prognostic stratification of DLBCL. Increasing evidence has demonstrated that dysregulated metabolic processes contribute to the initiation and progression of DLBCL. Metabolic competition within the tumor microenvironment is also known to influence immune cell metabolism. However, metabolism- and immune-related stratification has not been established. Here, 1660 genes involved in 84 metabolic pathways were selected and tested to establish metabolic clusters (MECs) of DLBCL. MECs established based on independent lymphoma datasets distinguished different survival outcomes. The CIBERSORT algorithm and EcoTyper were applied to quantify the relative abundance of immune cell types and identify variation in cell states for 13 lineages comprising the tumor micro environment among different MECs, respectively. Functional characterization showed that MECs were an indicator of the immune microenvironment and correlated with distinctive mutational characteristics and oncogenic signaling pathways. The novel immune-related MECs exhibited promising clinical prognostic value and potential for informing DLBCL treatment decisions.

Semimethylation is a feature of diffuse large B-cell lymphoma, and subgroups with poor prognosis are characterized by global hypomethylation and short telomere length.

BACKGROUND: Large B-cell lymphoma (LBCL) is the most common lymphoma and is known to be a biologically heterogeneous disease regarding genetic, phenotypic, and clinical features. Although the prognosis is good, one-third has a primary refractory or relapsing disease which underscores the importance of developing predictive biological markers capable of identifying high- and low-risk patients. DNA methylation (DNAm) and telomere maintenance alterations are hallmarks of cancer and aging. Both these alterations may contribute to the heterogeneity of the disease, and potentially influence the prognosis of LBCL. RESULTS: We studied the DNAm profiles (Infinium MethylationEPIC BeadChip) and relative telomere lengths (RTL) with qPCR of 93 LBCL cases: Diffuse large B-cell lymphoma not otherwise specified (DLBCL, n = 66), High-grade B-cell lymphoma (n = 7), Primary CNS lymphoma (n = 8), and transformation of indolent B-cell lymphoma (n = 12). There was a substantial methylation heterogeneity in DLBCL and other LBCL entities compared to normal cells and other B-cell neoplasms. LBCL cases had a particularly aberrant semimethylated pattern (0.15 ≤ ß ≤ 0.8) with large intertumor variation and overall low hypermethylation (ß > 0.8). DNAm patterns could not be used to distinguish between germinal center B-cell-like (GC) and non-GC DLBCL cases. In cases treated with R-CHOP-like regimens, a high percentage of global hypomethylation (ß < 0.15) was in multivariable analysis associated with worse disease-specific survival (DSS) (HR 6.920, 95% CI 1.499-31.943) and progression-free survival (PFS) (HR 4.923, 95% CI 1.286-18.849) in DLBCL and with worse DSS (HR 5.147, 95% CI 1.239-21.388) in LBCL. These cases with a high percentage of global hypomethylation also had a higher degree of CpG island methylation, including islands in promoter-associated regions, than the cases with less hypomethylation. Additionally, telomere length was heterogenous in LBCL, with a subset of the DLBCL-GC cases accounting for the longest RTL. Short RTL was independently associated with worse DSS (HR 6.011, 95% CI 1.319-27.397) and PFS (HR 4.689, 95% CI 1.102-19.963) in LBCL treated with R-CHOP-like regimens. CONCLUSION: We hypothesize that subclones with high global hypomethylation and hypermethylated CpG islands could have advantages in tumor progression, e.g. by inactivating tumor suppressor genes or promoting treatment resistance. Our findings suggest that cases with high global hypomethylation and thus poor prognosis could be candidates for alternative treatment regimens including hypomethylating drugs.

Hematological ratios and indices in canine large B-cell lymphoma.

Background: Canine lymphoma is the most common hematopoietic cancer in dogs. Numerous studies have evaluated the prognostic value of hematological abnormalities and ratios in both humans and dogs with lymphoma. Aim: To compare hematological parameters and complete blood count ratios between a population of dogs affected by lymphoma and healthy dogs to identify potential prognostic markers for lymphoma. Methods: This retrospective case-control study compares hematological parameters and complete blood count ratios between a population of 114 dogs affected by multicentric large B-cell lymphoma (LBCL) and 60 healthy dogs. Results: The study found several statistically significant differences between the hematological indices of LBCL dogs and healthy dogs, but no correlation between these parameters and the survival times of 78 dogs treated with chemotherapy Madison Wisconsin protocol. In addition, hematological alterations were evaluated such as anemia, leukocytosis, and thrombocytopenia. Conclusion: Hematological ratios have been suggested as potential prognostic markers for canine LBCL but their real prognostic value remains controversial and requires future investigation.

A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma.

BACKGROUND: Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL). METHODS: We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay. RESULTS: The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL. CONCLUSION: The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.

Are we closer to a standard of care for Richter's syndrome? Novel treatments on the horizon.

INTRODUCTION: The therapeutic landscape for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved over the past decade with dramatically improved outcomes with the introduction of targeted therapies. This unfortunately has not been the case for Richter transformation (RT), the histologic transformation to a more aggressive lymphoma, most typically diffuse large B-cell lymphoma (DLBCL). As such, RT continues to be one of the most challenging complications of CLL/SLL. Historically, RT has a poor response to treatment, with a minority reaching complete remission (CR) and overall survival (OS) being less than a year. AREAS COVERED: The focus of this review is to discuss the effectiveness of commonly used regimens, and review existing data for emerging regimens being examined in ongoing clinical trials to improve prognosis and outcomes in patients with RT. Despite extensive efforts to optimize therapies for RT, there is still no generalized consensus on either first-line treatment regimens or regimens in the relapsed/refractory setting. RT continues to carry a high mortality rate without durable response to current therapeutic agents. EXPERT OPINION: Ongoing and future research may identify novel treatment approaches that will eventually improve outcomes for patients with RT. The optimal care for RT patients is a clinical trial, when feasible.

High PPP4C expression predicts poor prognosis in diffuse large B-cell lymphoma.

The significance of Protein phosphatase 4 catalytic subunit (PPP4C) in diffuse large B-cell lymphoma (DLBCL) prognosis is not well understood. This work aimed to investigate the expression of PPP4C in DLBCL, investigate the correlation between PPP4C expression and clinicopathological parameters, and assess the prognostic significance of PPP4C. The mRNA expression of PPP4C was investigated using data from TCGA and GEO. To further analyze PPP4C expression, immunohistochemistry was performed on tissue microarray samples. Correlation analysis between clinicopathological parameters and PPP4C expression was conducted using Pearson's chi-square test or Fisher's exact test. Univariate and multivariate Cox hazard models were utilized to determine the prognostic significance of clinicopathological features and PPP4C expression. Additionally, survival analysis was performed using Kaplan-Meier survival curves. In both TCGA and GEO datasets, we identified higher mRNA levels of PPP4C in tumor tissues compared to normal tissues. Upon analysis of various clinicopathological features of DLBCL, we observed a correlation between high PPP4C expression and ECOG score (P = 0.003). Furthermore, according to a Kaplan-Meier survival analysis, patients with DLBCL who exhibit high levels of PPP4C had worse overall survival (P = 0.001) and progression-free survival (P = 0.002). PPP4C was shown to be an independent predictive factor for OS and PFS in DLBCL by univariate and multivariate analysis (P = 0.011 and P = 0.040). This study's findings indicate that high expression of PPP4C is linked to a poor prognosis for DLBCL and may function as an independent prognostic factors.

Testing for t(3;8) in MYC/BCL6-rearranged large B-cell lymphoma identifies a high-risk subgroup with inferior survival.

ABSTRACT: A reciprocal t(3;8) BCL6::MYC fusion is common in large B-cell lymphoma (LBCL) with MYC and BCL6 disruption. These pseudo-double-hit cases are not adverse, whereas t(3;8)-MYC/BCL6 lymphoma has an inferior prognosis relative to other MYC-rearranged LBCL.