Diffuse Large B-cell Lymphoma Patients Research Articles

Cell-Free Circulating DNA as a Prognostic Factor for Diffuse Large B-Cell Lymphoma (DLBCL) Patients With Hepatitis C Virus (HCV)

Cell-Free Circulating DNA as a Prognostic Factor for Diffuse Large B-Cell Lymphoma (DLBCL) Patients With Hepatitis C Virus (HCV)

NEAT1 and CHROMR lncRNAs: a promising diagnostic tool for diffuse large B-cell lymphoma especially in elderly patients.

Background: Long non-coding (lnc) RNAs have crucial regulatory roles in molecular pathways, and their dysregulation is associated with the pathogenesis of malignancies such as Diffuse large B-cell lymphoma (DLBCL). Therefore, we aimed to study the NEAT1 and CHROMR expression in DLBCL and explore their association with clinicopathological characteristics.Methods & materials: DLBCL and non-tumor lymph node specimens were obtained to assess the expression levels.Results: NEAT1 and CHROMR expressions were significantly increased in DLBCL, and were linked with the age of DLBCL patients (aged >60). NEAT1 and CHROMR overexpression may serve as moderate-to-good diagnostic biomarkers, with NEAT1 and CHROMR exhibiting area under the curve values of 0.781 and 0.831, respectively.

Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms

TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.

Predicting lymphoma prognosis using machine learning-based genes associated with lactylation

BackgroundLactylation, a newly discovered PTM involving lactic acid, is linked to solid tumor proliferation and metastasis. Lymphoma patients exhibit high lactic acid levels, yet lactylation's role in lymphoma is underexplored. This study aimed to identify lactylation-related genes in lymphoma using tumor databases and assess their predictive value in patient prognosis through cell experiments and clinical specimens. MethodsUsing TCGA and GEO datasets, we analyzed the expression levels of lactylation-related genes in diffuse large B-cell lymphoma patients. We also evaluated the prognostic significance of lactylation gene risk scores, exploring their impact on drug sensitivity and tumor immune function. Key lactylation-affecting genes were identified and functionally validated through cell experiments and mouse in vivo experiments. Additionally, the relationship between lactylation and lymphoma prognosis was examined in clinical specimens. ResultsWe identified 70 genes linked to diffuse large B-cell lymphoma prognosis from the lactylation-related gene set. Using clinical data and a COX regression algorithm, we developed an optimized lactylation Riskscore model. This model significantly correlated with prognosis and showed differences in immune cell infiltration, particularly macrophages. High-risk patients showed resistance to chemotherapy drugs but responded well to immunotherapy. HNRNPH1, a lactylation-related gene, influenced patient prognosis, apoptosis, cell cycle distribution in lymphoma cells, and tumor volume in mice. In lymphoma specimens, lactylation levels correlated with Bcl-2, C-myc, and P53 levels. ConclusionsLactylation impacts diffuse large B-cell lymphoma prognosis, tumor immune function, and drug resistance. Our lactylation-based Riskscore model aids in patient stratification and treatment selection. HNRNPH1 regulates lactylation, thereby affecting patient prognosis.

Prognostic stratification in DLBCL patients with aberrant MYC gene.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a subset of patients who exhibit treatment resistance and poor prognoses. Genomic assays have been widely employed to identify high-risk individuals characterized by rearrangements in the MYC, BCL2 and BCL6 genes. These patients typically undergo more aggressive therapeutic treatments; however, there remains a significant variation in their treatment outcomes. This study introduces an MYC signature score (MYCSS) derived from gene expression profiles, specifically designed to evaluate MYC overactivation in DLBCL patients. MYCSS was validated across several independent cohorts to assess its ability to stratify patients based on MYC-related genetic and molecular aberrations, enhancing the accuracy of prognostic evaluations compared to conventional MYC biomarkers. Our results indicate that MYCSS significantly refines prognostic accuracy beyond that of conventional MYC biomarkers focused on genetic aberrations. More importantly, we found that nearly 50% of patients identified as high risk by traditional MYC metrics actually share similar survival prospects with those having no MYC aberrations. These patients may benefit from standard GCB-based therapies rather than more aggressive treatments. MYCSS provides a robust signature that identifies high-risk patients, aiding in the precision treatment of DLBCL, and minimizing the potential for overtreatment.

Effect of Vitamin D and Skeletal Muscle Mass on Prognosis of Patients with Diffuse Large B-Cell Lymphoma.

This study investigated the prognostic impact of vitamin D deficiency and reduced skeletal muscle mass in diffuse large B-cell lymphoma (DLBCL) patients. A retrospective analysis of 186 newly diagnosed DLBCL patients from 2012 to 2022 was conducted, measuring serum 25-hydroxyvitamin D [25(OH)D] levels and the skeletal muscle index (SMI). Decreased vitamin D levels were linked to more severe DLBCL disease, with a median 25(OH)D concentration of 13 (4.0-27) ng/mL. Males in the group with a low SMI had a considerably lower 25(OH)D concentration. The optimal threshold of 25(OH)D levels for overall survival (OS) was 9.6 ng/mL, with lower values associated with a higher likelihood of recurrence and mortality. Multivariable analysis showed hazard ratios for OS of 1.4 [95% CI 0.77-2.5] for a low SMI and 3.2 [95% CI 1.8-5.8] for low 25(OH)D concentration. The combination of a low SMI and low vitamin D concentration resulted in the worst prognosis. Thus, low levels of vitamin D associated with disease progression significantly impact DLBCL prognosis, which can be further stratified by the SMI, providing valuable insights for patient management and potential therapeutic interventions.

Association between skeletal muscle mass and treatment response in patients with diffuse large B-cell lymphoma

Previous studies have demonstrated that a low skeletal muscle mass (SMM) is an adverse factor for overall survival (OS) in diffuse large B-cell lymphoma (DLBCL). However, its association with the treatment response has not been extensively investigated. This study aimed to determine the association between low skeletal muscle mass (SMM) and treatment response in DLBCL patients. We conducted a retrospective cohort study of 123 patients with DLBCL, in whom SMM was assessed using computed tomography before chemotherapy administration. The demographic characteristics of the patients with low SMM and those with normal SMM were not statistically different. However, there were notable differences in weight and BMI; patients with low SMM had a lower mean weight (59.2 vs 63, p = 0.002) and a higher proportion of patients with normal BMI (61.5% vs. 21.1%, p < 0.001). In addition, patients with low SMM were more likely to receive R-CHOP-like treatment (21.2% vs. 7%, p = 0.022) and experienced more delays in administration (42.9% vs. 33.3%, p = 0.452). Low SMM was not associated with failure to achieve CR (HR 1.9; 95% CI [0.9–4.1] p = 0.84), but it was reported to risk OS in univariate analysis (HR 2.1; 95% CI [1.03–4.2], p = 0.041). An interesting result was the interaction of low SMM with hypertension as a risk factor for not achieving CR (HR 2.7; 95% CI [1.1–6.5] p = 0.034) or OS (HR 7.9; 95% CI [3.4–18.8] p < 0.001). Low SMM was not a risk factor for achieving CR in patients with DLBCL and seemed to play a role in OS.

Assessing the impact of aprepitant on response to dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP).

Despite evidence demonstrating the effectiveness of aprepitant for chemotherapy-induced nausea and vomiting (CINV), its use in stem cell transplant settings across Canada is not standard. While pharmacokinetic data exists, the clinical significance of cytochrome P450 3A4 (CYP 3A4) inhibition of cyclophosphamide by aprepitant is unclear. Reduced activation of cyclophosphamide may reduce the effectiveness of dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). To compare response rates to DICEP in patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) in the presence and absence of aprepitant. A retrospective review of patients who received full-dose DICEP for relapsed/refractory HL or DLBCL between June 1995 and September 2018 at the Foothills Medical Centre (FMC) in Calgary, Alberta, Canada was conducted. Descriptive statistics were used to assess response rate, as defined by the 2007 International Working Group response criteria. Of the 218 patients included in this study, 87.6% of patients in the control group and 88.5% of patients in the aprepitant group responded to DICEP (difference 0.025 [95% CI, -0.066 to 0.114], p = 0.827). Univariate analyses for age, sex, type of cancer, stage of cancer, number of prior relapses, and relapse status were not significant. No significant differences were observed for secondary outcomes. Response rates to DICEP in relapsed/refractory HL and DLBCL patients were similar regardless of aprepitant use. Considering these results and the effectiveness of aprepitant in CINV, its addition to standard antiemetic therapy in patients receiving DICEP should be given strong consideration in the transplant setting.

Clinical characteristics and outcome of early-stage diffuse large B cell lymphoma of female genital track: A retrospective study of the Hellenic cooperative lymphoma group.

Involvement of female genital track (FGT) by diffuse large B cell lymphoma (DLBCL) represents an extremely rare diagnosis. Especially data regarding early-stage disease (i.e., IE, IIE) is very limited. Importantly, previous studies showed controversial results about the risk of central nervous system (CNS) relapse in this entity. Herein, we describe one of the largest reported real-world series of patients with early-stage FGT DLBCL aiming to investigate the clinicopathological characteristics, response to therapy and survival outcomes in the era of immunochemotherapy. We analyzed 21 consecutive patients with biopsy proven DLBCL from uterus or ovary classified as stage IE or IIE out of 1905 newly diagnosed DLBCL patients (1.1%). Uterine and ovarian localization was observed in 14 and seven patients, respectively. Median age was 66years (range 33-96); 9/21 (43%) were <55years. Regarding Cell of Origin DLBCL subtype, Germinal Center B-cell subtype was found in seven patients, non-GCB in 10 and non-classified in 4 patients. Median follow-up was 57months and 5-year overall survival, lymphoma specific survival and Freedom from Progression were 78%, 89% and 90%, respectively. There was no correlation of patients' characteristics with survival parameters. Interestingly, none of the patients experienced CNS relapse. Our results indicate that localized FGT DLBCL exhibits a good prognosis and may not increase the risk for secondary CNS involvement.

DNA mismatch repair defect and intratumor heterogeneous deficiency differently impact immune responses in diffuse large B-cell lymphoma

ABSTRACT Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression profiling. The results showed that genetic dMMR was infrequent in DLBCL and was significantly associated with increased cancer gene mutations and favorable immune microenvironment, but not prognostic impact. Phenotypic dMMR was also infrequent, and MMR proteins were commonly expressed in DLBCL. However, intratumor heterogeneity existed, and increased DLBCL cells with phenotypic dMMR correlated with significantly increased T cells and PD-1+ T cells, higher average nearest neighbor distance between T cells and PAX5+ cells, upregulated immune gene signatures, LE4 and LE7 ecotypes and their underlying Ecotyper-defined cell states, suggesting the possibility that increased T cells targeted only tumor cell subsets with dMMR. Only in patients with MYC¯ DLBCL, high MSH6/PMS2 expression showed significant adverse prognostic effects. This study shows the immunologic and prognostic effects of genetic/phenotypic dMMR in DLBCL, and raises a question on whether DLBCL-infiltrating PD-1+ T cells target only tumor subclones, relevant for the efficacy of PD-1 blockade immunotherapy in DLBCL.

BCL6 confers resistance to HDAC inhibitors in DLBCL

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with limited response to chemotherapy. Histone acetylation is reduced in DLBCL. Chidamide, a histone deacetylase inhibitor, shows promise in lymphomas but needs further investigation for DLBCL. Our study indicated that chidamide effectively suppresses DLBCL both in vitro and in vivo. High-throughput RNA sequencing analysis provided comprehensive evidence that chidamide markedly influences crucial signaling pathways in DLBCL, including the MAPK, MYC and p53 pathway. Additionally, we observed substantial variability in the sensitivity of DLBCL cells to chidamide, and identified that elevated expression of BCL6 might confer resistance to chidamide in DLBCL. Moreover, our investigations revealed that BCL6 inhibited chidamide-induced histone acetylation by recruiting histone deacetylase (HDACs), leading to drug resistance in DLBCL cells. Furthermore, we found that lenalidomide targeted BCL6 degradation through the ubiquitination pathway and restore the sensitivity of drug-resistant DLBCL to chidamide. Collectively, these findings provided valuable insights into the global impact of chidamide on DLBCL and highlight the potential of targeting HDACs as a therapeutic strategy for DLBCL. Identifying BCL6 as a biomarker for predicting the response to chidamide and the combination therapy with BCL6 inhibition has the potential to lead to more personalized and effective treatments for DLBCL patients.

Volumetric and textural analysis of PET/CT in patients with diffuse large B-cell lymphoma highlights the importance of novel MTVrate feature.

To investigate the prognostic value of clinical, volumetric, and radiomics-based textural parameters in baseline [18F]FDG-PET/CT scans of diffuse large B-cell lymphoma (DLBCL) patients. We retrospectively investigated baseline PET/CT scans and collected clinical data of fifty DLBCL patients. PET images were segmented semiautomatically to determine metabolic tumor volume (MTV), then the largest segmented lymphoma volume of interest (VOI) was used to extract first-, second-, and high-order textural features. A novel value, MTVrate was introduced as the quotient of the largest lesion's volume and total body MTV. Receiver operating characteristics (ROC) analyses were performed and 24-months progression-free survival (PFS) of low- and high-risk cohorts were compared by log-rank analyses. A machine learning algorithm was used to build a prognostic model from the available clinical, volumetric, and textural data based on logistic regression. The area-under-the-curve (AUC) on ROC analysis was the highest of MTVrate at 0.74, followed by lactate-dehydrogenase, MTV, and skewness, with AUCs of 0.68, 0.63, and 0.55, respectively which parameters were also able to differentiate the PFS. A combined survival analysis including MTV and MTVrate identified a subgroup with particularly low PFS at 38%. In the machine learning-based model had an AUC of 0.83 and the highest relative importance was attributed to three textural features and both MTV and MTVrate as important predictors of PFS. Individual evaluation of different biomarkers yielded only limited prognostic data, whereas a machine learning-based combined analysis had higher effectivity. MTVrate had the highest prognostic ability on individual analysis and, combined with MTV, it identified a patient group with particularly poor prognosis.

Prognostic Value of LMR and CD163+TAM for Patients with Diffuse Large B Cell Lymphoma

To investigate the prognostic value of lymphocyte-to-monocyte ratio (LMR) and CD163+tumor-associated macrophages (TAM) in patients with diffuse large B cell lymphoma (DLBCL). Peripheral blood and lymph node tissues were collected from 63 newly diagnosed DLBCL patients. LMR was calculated by the number of lymphocytes and monocytes in peripheral blood from the result of blood routine examination. The level of CD163+TAM in lymph nodes was detected by immunohistochemistry. The cut-off values of LMR and CD163+TAM were determined by ROC curves, and the prognostic value of LMR and CD163+TAM in DLBCL patients was analyzed. The LMR level of 63 newly diagnosed DLBCL patients was 3.69±1.71, and the median value of CD163+TAM was 26/HPF. The number of CD163+TAM was negatively correlated with LMR (r =-0.58) and positively correlated with monocyte count (r =0.46). The cut-off values of LMR and CD163+TAM determined by ROC curve were 2.95 and 29/HPF, respectively, and based on this, the patients were divided into low LMR group and high LMR group, as well as low CD163+TAM group and high CD163+TAM group. The proportion of patients with clinical stage III-IV, IPI score 3-5 and bone marrow infiltration in the low LMR group were higher than those in the high LMR group (P < 0.05). The proportion of patients with clinical stage III-IV, IPI score 3-5, elevated LDH level and bone marrow infiltration in the high CD163+TAM group were higher than those in the low CD163+TAM group (P < 0.05). There was a positive correlation between LMR and OS (r =0.43) and a negative correlation between CD163+TAM and OS (r =-0.65). DLBCL patients with low LMR and high CD163+TAM had shorter OS (P < 0.05). Low LMR and high CD163+TAM can be used as biological markers for poor prognosis of DLBCL patients.

Low NDRG2, regulated by the MYC/MIZ-1 complex and methylation, predicts poor outcomes in DLBCL patients.

Diffuse large B-cell lymphoma (DLBCL) represents the most common tumor in non-Hodgkin's lymphoma. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor highly expressed in healthy tissues but downregulated in many cancers. Although cell proliferation-related metabolism rewiring has been well characterized, less is known about the mechanism of metabolic changes with DLBCL. Herein, we investigated the expressions of NDRG2, MYC and Myc-interacting zinc finger protein 1 (MIZ-1) in seven human lymphoma (mostly DLBCLs) cell lines. NDRG2 expression was inversely correlated with the expressions of MYC and MIZ-1. Further, we explored the regulatory mechanism and biological functions underlying the lymphomagenesis involving NDRG2, MYC and MIZ-1. MYC and MIZ-1 promoted DLBCL cell proliferation, while NDRG2 induced apoptosis in LY8 cells. Moreover, NDRG2 methylation was reversed by the 5-Aza-2'-deoxycytidine (5-Aza-CDR) treatment, triggering the downregulation of MYC and inhibiting DLBCL cell survival. MYC interacts with NDRG2 to regulate energy metabolism associated with mTOR. Remarkably, supporting the biological significance, the converse correlation between NDRG2 and MYC was observed in human DLBCL tumor tissues (R = -0.557). Bioinformatics analysis further validated the association among NDRG2, MYC, MIZ-1, mTOR, and related metabolism genes. Additionally, NDRG2 (P = 0.001) and MYC (P < 0.001) were identified as promising prognostic biomarkers in DLBCL patients through survival analysis. Together, our data demonstrate that the MYC/MIZ-1 complex interplays with NDRG2 to influence the proliferation and apoptosis of DLBCL cells and show the characterizations of NDRG2, MYC and MIZ-1 for metabolism features and prediction prognosis in DLBCL.

Primary Extranodal Diffuse Large B-Cell Lymphoma in the Rituximab Era: a Single-Center Retrospective Analysis

To investigate the clinical features and prognostic factors of patients with primary extranodal diffuse large B-cell lymphoma (DLBCL) in the rituximab era. The continuous data of newly diagnosed DLBCL patients with complete case data and first-line treated with rituximab, cyclophosphamide, epirubicin, vincristine, prednisone (R-CHOP) or R-CHOP treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to November 2023 were retrospectively analyzed. The clinical and molecular immunological features and prognosis of extranodal DLBCL were analyzed, Logistics regression model was used to analyzed the influencing factors of patients prognosis. A total of 237 patients were enrolled, of which 54.4% (129 cases) were primary extranodal sources of DLBCL, and the most common extranodal sites were as follows: stomach (19.4%), colon (14.7%), tonsils (12.4%), skin/muscle (9.3%), central (7.7%), nasal/nasopharynx (6.2%), bone marrow (5.4%), testes (4.7%). The 3-year PFS and OS of DLBCL patients with extranodal involvement of bone marrow, central, liver, gastrointestinal or pulmonary origin were significantly lower than those of other patients with extranodal DLBCL of non-special site origin, and the difference was statistically significant (PFS: 65.2% vs 76.7%, P =0.008; OS: 82.6% vs 88.3%, P =0.04). Multivariate analysis showed that the prognostic factors affecting OS included NCCN-IPI score >3 (OR : 0.142, 95%CI : 0.041-0.495, P =0.002), non-germinal center source (OR : 2.675，95%CI :1.069-6.694，P =0.036), and DEL patients (OR : 0.327, 95%CI : 0.129-0.830, P =0.019). An NCCN-IPI score >3 was the only independent adverse prognostic factor for PFS (OR : 0.235, 95%CI : 0.116-0.474, P < 0.001). Patients with primary extranodal source DLBCL are more common in gastrointestinal involvement, and the overall prognosis is worse than that of patients with lymph node origin. NCCN-IPI score is an important independent adverse prognostic factor for predicting overall survival and progression-free survival in patients with primary extranodal diffuse large B-cell lymphoma.

Enhanced prognostic evaluation of diffuse large B-cell lymphoma: A comprehensive surveillance study incorporating Epstein-Barr virus infection status and immunohistochemical markers.

Emerging biologic subsets and new prognostic markers are significantly important for aggressive diffuse large B-cell lymphoma (DLBCL). Nevertheless, the high cost of testing limits the availability of these tests in most hospitals, thus making prognostic judgment based on basic immunohistochemical testing, whole blood Epstein-Barr virus DNA (WBEBV) surveillance and clinical features advantageous for hospitals and patients with poor medical conditions. We included 647 DLBCL patients treated in our hospital from January 2009 to March 2023. Non-germinal center B-cell like, Ki-67, and International Prognostic Index(IPI) scores were related to cMYC/B-cell lymphoma 2 (Bcl-2)-double expression. Age, Epstein-Barr virus-encoded small RNA(EBER) positivity, and IPIscores were associated with mortality. The cutoffs for differential overall survival (OS) of age, WBEBV, Bcl-2, and cMYC were 57 years, 1514 copies/mL (baseline), 5.89 × 104 copies/mL (treatment), 40%, and 55%, respectively. EBER positivity was significantly associated with a worse OS. Patients with newly defined DE (Bcl-2 ≥ 40 and cMYC > 55) had a worse prognosis than controls (p = 0.04). We found that cMYC with an optimal cutoff of 47.5 could effectively predict high-grade DLBCL with an area under the curve of 0.912, and the specificity and sensitivity were 70.7% and 100%, respectively. Our study provides valuable insights into the prognostic factors and biomarker cutoffs that influence OS in DLBCL patients, which may guide clinicians in tailoring treatment strategies and improving patient outcomes.

Prognostic Role of Neutrophil to Lymphocyte Ratio at Diagnosis in Patients with Diffuse Large B-Cell Lymphoma.

Aim to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR) at the time of diagnosis, which is an inexpensive and easily accessible parameter, compared to factors known as prognostic value (such as R-IPI and NCCN-IPI) in patients with diffuse large B-cell lymphoma (DLBCL). Prognostic value of NLR at diagnosis in DLBCL. A hundred (100) newly diagnosed DLBCL patients were included. The correlations between the NLR with clinical characteristics, treatment response, and survival were analyzed. The NLR cut-off value was taken at 3.5 accordıng to the receiver operating characteristic curve. There were 53 patients with an NLR of 3.5 and 47 patients with an NLR < 3.5. Patients with NLR ≥ 3.5 had a complete response (CR) rate of 66.0% (n = 31/47), and patients with NLR < 3.5 had a CR rate of 98.1% (n = 51/52). The median progression-free survival (PFS) was 132.5 months (95%CI 103.1-162.0). PFS in the NLR ≥ 3.5 group (36 months) was significantly (P < 0.000) shorter than in the NLR < 3.5 group (185 months). The median overall survival (OS) for NLR ≥ 3.5 and NLR < 3.5 was 79.2 months (95% CI 51.6-106.8) and 197.8 months (95% CI 173.2-222.5), respectively. NLR ≥ 3.5 was associated with worse OS than NLR < 3.5 (P = 0.000). The high value of NLR (≥3.5) had lower treatment response rates, higher relapse, and death rates. High NLR was associated with poor treatment response, PFS, and OS. NLR can be used as a cost-effective and easy-to-interpret prognostic marker in DLBCL patients.

Systemic Inflammatory Markers Can Improve Survival Prediction of Patients with Diffuse Large B-Cell Lymphoma: Model Development and Evaluation

To establish a model to predict the overall survival (OS) rate of patients with diffuse large B-cell lymphoma (DLBCL) based on systemic inflammatory indicators, and study whether the new model combined with inflammatory related parameters is more effective than the conventional model using only clinical factors to predict the OS of patients with DLBCL. The clinical data of 213 patients with DLBCL were analyzed retrospectively. Backward stepwise Cox regression analysis was used to screen independent prognostic factors related to OS, and a nomogram for predicting OS was constructed based on these factors. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to evaluate the fitting of the model, the consistency index (C-index), area under receiver operating characteristic (ROC) curve (AUC) and calibration curve were used to evaluate the prediction accuracy of nomogram, and decision curve analysis (DCA) and Kaplan Meier curve were used to evaluate the clinical practicability of nomogram. Multivariate analysis confirmed that age, ECOG PS score, serum lactate dehydrogenase (LDH) level, systemic immune inflammatory index (SII), and prognostic nutritional index (PNI) were used to construct the nomogram. The AIC and BIC of the nomogram were lower than the International Prognostic Index (IPI) and the National Comprehensive Cancer Network (NCCN)-IPI, indicating that the nomogram had better goodness of fit. The C-index and AUC of the nomogram were higher than IPI and NCCN-IPI, indicating that the prediction accuracy of the nomogram had been significantly improved, and the calibration curve showed that the prediction results were in good agreement with the actual survival results. DCA showed that the nomogram had better clinical net income. Kaplan Meier curve showed that patients could be well divided into low-risk, medium-risk and high-risk groups according to the nomogram score (P < 0.001). The nomogram combined with inflammatory indicators can accurately predict the individual survival probability of DLBCL patients.

Prognostic value of lactate dehydrogenase to absolute lymphocyte count ratio and albumin to fibrinogen ratio in diffuse large B-cell lymphoma.

With the continuous improvement of treatment strategy, the prognostic value of international prognostic index (IPI) alone is limited for diffuse large B-cell lymphoma (DLBCL). Our study aims to explore the effect of lactate dehydrogenase (LDH)to absolute lymphocyte count (ALC) ratio (LAR) and albumin to fibrinogen ratio (AFR) on the prognosis of patients with DLBCL. The venous blood LDH, ALC, albumin and fibrinogen within 1 week before the first chemotherapy in 74 DLBCL patients were collected to calculate the LAR and AFR values. The impact of LAR and AFR on the progression-free survival (PFS) of patients with DLBCL was studied by the survival analysis. The area under the receiver operating characteristic curve (AUC) and concordance index (C-index) were used to analyze the predictive efficiency of each model for the PFS of DLBCL patients. Cox univariate analysis suggested that elevated LAR (P < .001) and decreased AFR (P < .001) were risk factors for PFS in DLBCL patients. Multivariate analysis revealed that LAR (P < .001) and AFR (P = .004) were 2 independent prognostic parameters. The AUC values of IPI, AFR + IPI, LAR + IPI and AFR + LAR + IPI to predict the PFS of DLBCL patients were 0.806 (95%CI 0.707-0.905, P < .001), 0.839 (95%CI 0.747-0.932, P < .001), 0.851 (95%CI 0.764-0.938, P < .001), and 0.869 (95%CI 0.787-0.952, P < .001), respectively. The C-index values of above 4 models were 0.802 (95%CI 0.629-0.975, P < .001), 0.842 (95% CI 0.735-0.949, P < .001), 0.846 (95%CI 0.716-0.976, P < .001), and 0.864 (95%CI 0.781-0.941, P < .001), respectively. The results suggest that both LAR and AFR are independent prognostic factors for PFS in DLBCL patients. Furthermore, their combination with IPI has better predictive efficiency for the prognosis of DLBCL patients.

Metabolic tumour area: a novel prognostic indicator based on 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma in the R-CHOP era

BackgroundThe metabolic tumour area (MTA) was found to be a promising predictor of prostate cancer. However, the role of MTA based on 18F-FDG PET/CT in diffuse large B-cell lymphoma (DLBCL) prognosis remains unclear. This study aimed to elucidate the prognostic significance of MTA and evaluate its incremental value to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) for DLBCL patients treated with first-line R-CHOP regimens.MethodsA total of 280 consecutive patients with newly diagnosed DLBCL and baseline 18F-FDG PET/CT data were retrospectively evaluated. Lesions were delineated via a semiautomated segmentation method based on a 41% SUVmax threshold to estimate semiquantitative metabolic parameters such as total metabolic tumour volume (TMTV) and MTA. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values. Progression-free survival (PFS) and overall survival (OS) were the endpoints that were used to evaluate the prognosis. PFS and OS were estimated via Kaplan‒Meier curves and compared via the log-rank test.ResultsUnivariate analysis revealed that patients with high MTA, high TMTV and NCCN-IPI ≥ 4 were associated with inferior PFS and OS (P < 0.0001 for all). Multivariate analysis indicated that MTA remained an independent predictor of PFS and OS [hazard ratio (HR), 2.506; 95% confidence interval (CI), 1.337–4.696; P = 0.004; and HR, 1.823; 95% CI, 1.005–3.310; P = 0.048], whereas TMTV was not. Further analysis using the NCCN-IPI model as a covariate revealed that MTA and NCCN-IPI were still independent predictors of PFS (HR, 2.617; 95% CI, 1.494–4.586; P = 0.001; and HR, 2.633; 95% CI, 1.650–4.203; P < 0.0001) and OS (HR, 2.021; 95% CI, 1.201–3.401; P = 0.008; and HR, 3.869; 95% CI, 1.959–7.640; P < 0.0001; respectively). Furthermore, MTA was used to separate patients with high NCCN-IPI risk scores into two groups with significantly different outcomes.ConclusionsPre-treatment MTA based on 18F-FDG PET/CT and NCCN-IPI were independent predictor of PFS and OS in DLBCL patients treated with R-CHOP. MTA has additional predictive value for the prognosis of patients with DLBCL, especially in high-risk patients with NCCN-IPI ≥ 4. In addition, the combination of MTA and NCCN-IPI may be helpful in further improving risk stratification and guiding individualised treatment options.Trial registrationThis research was retrospectively registered with the Ethics Committee of the Third Affiliated Hospital of Soochow University, and the registration number was approval No. 155 (approved date: 31 May 2022).