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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.

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INTRODUCTION: Chimeric antigen receptor T (CAR-T) cell therapy is an innovative technology that has shown promising results in clinical trials. Treatment is based on modifying the patient's own T cells to express artificial surface receptors to specifically recognize and attack the tumor cells. OBJECTIVE: To synthesize available evidence on the incidence and management strategies of cytokine release syndrome in patients with diffuse large B-cell lymphoma who received CAR-T cell therapy. METHODS: This is a systematic literature review. The search was conducted in the PubMed, Scopus, and Web of science databases. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The systematic review protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) database under number CRD42022359258. RESULTS: Nineteen studies were included with a total of 1193 patients who received CAR-T cell therapy. Of these patients, 804 (67%) developed some degree of cytokine release syndrome. The frequencies of Grade 3 and 4 cytokine release syndrome were 10% and 3%, respectively. The regimen most used in the management of the syndrome included tocilizumab and/or glucocorticoids. CONCLUSION: The results obtained in this review demonstrate high rates of cytokine release syndrome in patients with diffuse large B-cell lymphoma treated with CAR-T cell therapy, however these events are manageable, supporting the conclusion that this therapy is safe in these patients.

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PURPOSE: The objective of this investigation is to explore the capability of baseline 18F-FDG PET/CT radiomics to predict the prognosis of diffuse large B-cell lymphoma (DLBCL) with extranodal involvement (ENI). METHODS: 126 patients diagnosed with DLBCL with ENI were included in the cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to refine the optimum subset from the 1328 features. Cox regression analyses were employed to discern significant clinical variables and conventional PET parameters, which were then employed with radiomics score to develop combined model for predicting both progression-free survival (PFS) and overall survival (OS). The fitness and the predictive capability of the models were assessed via the Akaike information criterion (AIC) and concordance index (C-index). RESULTS: 62 patients experienced disease recurrence or progression and 28 patients ultimately died. The combined model exhibited a lower AIC value compared to the radiomics model and SDmax/clinical variables for both PFS (507.101 vs. 510.658 vs. 525.506) and OS (215.667 vs. 230.556 vs. 219.313), respectively. The C-indices of the combined model, radiomics model, and SDmax/clinical variables were 0.724, 0.704, and 0.615 for PFS, and 0.842, 0.744, and 0.792 for OS, respectively. Kaplan--Meier curves showed significantly higher rates of relapse and mortality among patients classified as high-risk compared to those classified as low-risk (all P < 0.05). CONCLUSIONS: The combined model of clinical variables, conventional PET parameters, and baseline PET/CT radiomics features demonstrates a higher accuracy in predicting the prognosis of DLBCL with ENI.

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Introduction: Diffuse large B-cell lymphoma (DLBCL), a prevalent non-Hodgkin lymphoma subtype, displays diverse clinical outcomes with persistently high mortality and relapse rates, despite treatment advancements. Notably, the Hispanic demographic lacks consideration in existing prognostic indices for DLBCL. Methods: A retrospective cohort study encompassing 112 DLBCL patients diagnosed between 2010 and 2020 was conducted at our institution. Patient data, including overall survival (OS), treatment response, and relapse, were analysed. Results: With a median age of 65 years and a predominant male population (60.7%), both the International Prognostic Index (IPI) and revised IPI correlated with OS. In multivariate analysis, patients with ki-67 ≥ 60% exhibited higher mortality risk (Hazard Ratio: 2.35, 95% confidence intervals (CI) 1.05-5.27, p = 0.039), even when controlled by IPI category and B2-microglobulin levels. The absence of B symptoms served as a protective factor for relapse (p < 0.01, OR: 0.147, 95% CI 0.058-0.376) when controlling for ki-67, CD5, and IPI. Conclusion: Our cohort demonstrated a 5-year OS rate comparable to high-income countries, highlighting the need for tailored prognostic models for Hispanic DLBCL patients. This study identifies easily accessible parameters aligning with regional resource constraints, providing insights into additional prognostic factors for DLBCL in the Hispanic population.

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INTRODUCTION: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. METHODS: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. RESULTS: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. CONCLUSION: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered".

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Primary gastrointestinal non-Hodgkin lymphoma, while rare, most often presents as diffuse large B-cell lymphoma located in the stomach or ileocecal region. Presenting symptoms include abdominal pain, gastrointestinal bleeding, weight loss, or obstructive symptoms. Imaging can reveal ileitis or obstruction. We report a case of a man from Honduras with latent tuberculosis and chronic hepatitis B who presented with features of Crohn's disease through clinical, radiologic, and endoscopic findings but was ultimately diagnosed with diffuse large B-cell lymphoma by histology. We emphasize the importance of maintaining a broad differential for ileitis and the importance of histologic sampling when evaluating ileitis.

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Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma. MIC-A and MIC-B are the natural ligands for NKG2D, a receptor expressed in NK cells. MIC-A soluble isoforms (sMICA) have been described in different malignancies. OBJECTIVES: To analyze lymphocyte subsets and sMIC-A in germinal center DLBCL. MATERIALS AND METHODS: sMICA, sMICB, and peripheral blood lymphocyte subsets (CD4+, CD8+, NK, NKT, γδ T cells, and dendritic cells) were analyzed in 59 patients and 60 healthy donors. RESULTS: Patients had decreased numbers of type 1 and type 2 dendritic cells, NK, iNKT, CD4 T, and CD8 T cells, and higher levels of sMIC-A. The 2-year PFS for high IPI scores and high sMIC-A was 24% and 28%, respectively. The 2-year OS for high IPI scores and high sMIC-A was 42% and 33%. The 2-year PFS and OS for patients not achieving response to treatment were 0% and 10%, respectively. The MICPI score (one point each for high IPI score and high sMIC-A) showed that those patients summing two points had worse PSF and OS. CONCLUSIONS: Patients with DLBCL have decreased numbers of peripheral lymphocyte subsets and high levels of sMIC-A. The addition of sMIC-A to IPI could improve its prognostic relevance.

Assuntos

Centro Germinativo , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Prognóstico , Centro Germinativo/patologia , Centro Germinativo/metabolismo , Adulto , Subpopulações de Linfócitos/metabolismo , Subpopulações de Linfócitos/imunologia , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Estadiamento de Neoplasias , Imunofenotipagem , Biomarcadores Tumorais

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Background: Primary central nervous system (CNS) lymphoma is a very rare extranodal non-Hodgkin lymphoma. The bilateral pattern, as we call it "mirror type", has been identified in other CNS lesions such as gliomas, metastases, and demyelinating lesions, so the differential diagnosis includes imaging studies such as magnetic resonance imaging contrasted with spectroscopy, ruling out immunodeficiency or metastatic disease. Case Description: A 65-year-old female presented progressing headache, loss of memory and language alterations, as well as sensory alterations. Neuroimaging showed the presence of two equidistant periventricular lesions at the level of both ventricular atria, a spectroscopy study suggestive of malignancy. Serological studies showed no evidence of immunodeficiency or the presence of positive tumor markers; however, a biopsy was performed, which revealed a histopathological result of primary lymphoma of the CNS. Conclusion: In neuro-oncology, primary CNS tumors with multiple lesions are rare, even more, the "mirror type" lesions. Lymphomas are lesions that can present in different ways on imaging and clinical presentation. These tumors that present a vector effect due to their size, perilesional edema, or that lead to loss of neurological function are highly discussed in diagnostic and surgical treatment. Due to their prognosis, action on diagnosis and treatment must be taken as quickly as hospital resources allow.

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PURPOSE: Mitogen-activated protein kinase 12 (MAPK12), also known as p38γ, is a member of the p38 MAPK family and plays a crucial role in tumor occurrence and invasion. However, there is still uncertainty regarding MAPK12 involvement in diffuse large B-cell lymphoma (DLBCL). METHODS: Our study investigated the expression of MAPK12 mRNA in various types of cancer using bioinformatic analysis. Furthermore, we performed immunohistochemistry (IHC) to detect the expression of MAPK12 in patients with DLBCL and compared clinical indicators and survival rates. RESULTS: We found that the high expression rate of MAPK12 was 43.1% in DLBCL patients. Several clinical indicators, including IPI scores, Hans classifications, LDH levels, and Ki-67 expression were closely associated with MAPK12 expression. Survival analysis revealed that higher expression of MAPK12 was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) in DLBCL patients. In addition, both univariate and multivariate analyses revealed IPI score, MAPK12 expression, and rituximab use as the independent OS risk factors (P < 0.05). To explore the functional role of MAPK12 in DLBCL, weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) were used to confirm the involvement of MAPK12 in the regulation of type II interferon production, positive regulation of lymphocyte proliferation, and other related biological processes. CONCLUSION: DLBCL patients have poor prognoses when MAPK12 levels are high, which is expected to be a therapeutic target and prognostic factor.

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BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) especially affects the older population. Old (≥60 years) and very old age (≥80 years) DLBCL patients often present high-risk molecular alterations, lower tolerability to conventional immunochemotherapy, and poor clinical outcomes. In this scenario, attenuated therapeutic strategies, such as the R-MiniCHOP and R-MiniCHOP of the elderly regimens, have emerged for this particularly fragile population. However, the responses, clinical outcomes, and toxicities of these regimens currently remain poorly understood, mainly because these individuals are not usually included in controlled clinical trials. METHODS: This retrospective, observational, and single-center real-world study included 185 DLBCL, NOS patients older than 70 years treated at the largest oncology center in Latin America from 2009 to 2020. We aimed to assess the outcomes, determine survival predictors, and compare responses and toxicities between three different primary therapeutic strategies, including the conventional R-CHOP regimen and the attenuated R-MiniCHOP and R-MiniCHOP of the elderly protocols. RESULTS: The median age at diagnosis was 75 years (70-97 years), and 58.9% were female. Comorbidities were prevalent, including 19.5% with immobility, 28.1% with malnutrition, and 24.8% with polypharmacy. Advanced clinical stage was observed in 72.4%, 48.6% had bulky disease ≥7 cm, 63.2% had B-symptoms, and 67.0% presented intermediate-high/high-risk IPI. With a median follow-up of 6.3 years, the estimated 5-year OS and PFS were 50.2% and 44.6%, respectively. The R-MiniCHOP of the elderly regimen had a lower ORR (p = 0.040); however, patients in this group had higher rates of unfavorable clinical and laboratory findings, including hypoalbuminemia (p = 0.001), IPI ≥ 3 (p = 0.013), and NCCN-IPI ≥ 3 (p = 0.002). Although associated with higher rates of severe neutropenia (p = 0.003), the R-CHOP regimen promoted increased OS (p = 0.003) and PFS (p = 0.005) in comparison to the attenuated protocols. Additionally, age ≥ 75 years, high levels of LDH, B-symptoms, advanced clinical stage (III/IV), neutrophilia, and low lymphocyte/monocyte ratio were identified as poor prognostic factors in this cohort. CONCLUSIONS: In this large and real-life Latin American cohort, we demonstrated that patients with DLBCL, NOS older than 70 years still do not have satisfactory clinical outcomes in 2024, with half of cases not reaching 5 years of life expectancy after diagnosis. Although the conventional R-CHOP offers response and survival advantages over attenuated regimens, its myelotoxicity is not negligible. Therefore, the outcomes reported and the prognostic factors here identified may assist clinicians in the appropriate selection of therapeutic strategies adapted to the risk for old and very old DLBCL patients.