Comparing 2-day vs 3-day flu-CY lymphodepleting regimens for CD19 CAR T-cell therapy in patients with non-hodgkin's lymphoma.

Introduction: Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency. Methods: We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity. Results: From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026). Discussion: As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.

Subsequent Malignancies after CD19-Targeted Chimeric Antigen Receptor T cells in Patients with Lymphoma.

Chimeric antigen receptor (CAR) T cells are an established treatment for B cell non-Hodgkin lymphomas (B-NHL). With the remarkable success in improving survival, understanding the late effects of CAR T cell therapy is becoming more relevant. The aim of this study is to determine the incidence of subsequent malignancies in adult patients with B-NHL. We retrospectively studied 355 patients from two different medical centers treated with four different CAR T cell products from 2016 to 2022. The overall cumulative incidence for subsequent malignancies at 36 months was 14% (95% CI: 9.2%, 19%). Subsequent malignancies were grouped into three primary categories: solid tumor, hematologic malignancy, and dermatologic malignancy with cumulative incidences at 36 months of 6.1% (95% CI: 3.1%-10%), 4.5% (95% CI: 2.1%-8.1%) and 4.2% (95% CI: 2.1%-7.5%) respectively. Notably, no cases of T cell malignancies were observed. In univariable analysis, increasing age was associated with higher risk for subsequent malignancy. While the overall benefits of CAR T products continue to outweigh their potential risks, more studies and longer follow ups are needed to further demonstrate the risks, patterns, and molecular pathways that lead to the development of subsequent malignancies.

A Case Report on a Rare Type of Lymphoma: Angioimmunoblastic T-cell Lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare type of non-Hodgkin lymphoma (NHL). We present a case of a 60-year-old female who attended the emergency department (ED) with fatigue, recurrent fever, weight loss, and adenopathy for six months. Laboratory findings showed anemia, lymphocytosis, eosinophilia, thrombocytosis, cholestasis, hypoproteinemia, and hypoalbuminemia. Abdominopelvic computed tomography (CT) revealed multiple adenopathies. A lymph node biopsy yielded inconclusive results in the outpatient clinic. Later, during admission, the patient underwent a positron emission tomography-computed tomography (PET-CT), revealing a cervical adenopathy cluster that was excised en bloc. Histology confirmed the diagnosis of AITL. The medical team initiated chemotherapy but opted for exclusive symptomatic treatment due to disease progression. The patient died six months after diagnosis. The fluctuating and nonspecific presentation of AITL can hinder and delay definitive diagnosis, therefore impacting treatment and prognosis.

FDG-PET/CT Imaging in Chimeric Antigen Receptor-Engineered T-Cell Treatment in Patients with B-Cell Lymphoma: Current Evidence.

The Food and Drug Administration and the European Medicines Agency have recently approved chimeric antigen receptor-engineered (CAR) T cells to treat several refractory/relapsed B-cell lymphomas. This comprehensive review aims to demonstrate the pivotal role that [18F]-FDG PET/computed tomographic (CT) imaging can play to enhance the care of patients treated with CAR T-cell therapy. To this end, this review deciphers evidence showing the diagnostic, prognostic, predictive, and theragnostic value of [18F]-FDG PET/CT-derived parameters.

Non-Hodgkin lymphoma presenting with spinal cord compression: A population-based analysis of the NHL-BFM study group.

BACKGROUND: Spinal cord compression is a rare presentation of non-Hodgkin lymphoma (NHL) in children. We aimed to describe the prevalence, histological subtypes, clinical presentation, therapy, and outcome of those children in a population-based cohort. The chemotherapy regimen remained comparable over time. METHODS: We retrospectively identified all children and adolescents with paresis as initial manifestations of the NHL between January 1990 and December 2020 from the NHL-BFM database. Characteristics, therapy, and outcome data were gathered from the database and patient files. RESULTS: Fifty-seven of 4779 children (1.2%) presented with initial paresis due to spinal cord compression. The median age was 10.3 years (range, 3.1-18.0 years), and 33% were female. Initial symptoms were paresis/weakness (n = 50, 88%), back pain (n = 33, 58%), paresthesia (n = 23, 40%), and bladder dysfunction and/or constipation (n = 22, 39%), persisting for a median of 14 days before diagnosis. Subtype distribution was mature B-NHL (n = 41, 72%), precursor B-lymphoblastic lymphoma (LBL) (n = 12, 21%), anaplastic large cell lymphoma (ALCL) (n = 3, 5%), and T-LBL (n = 1, 2%). Initial emergency therapy included surgery (70%) and/or chemotherapy/steroids (63%). Five-year event-free survival and overall survival (80% ± 5% and 82% ± 5%, respectively) were comparable with all other NHL patients. Neurological symptoms persisted in approximately one-third of surviving patients at the last follow-up. CONCLUSION: 1.2% of pediatric NHL patients presented with paresis from spinal cord compression mainly due to B-cell lymphomas. Neurological sequelae were observed in one-third of surviving patients.

Effective geriatric management strategies for fatal non-Hodgkin lymphoma: Insights from a case report. / Estrategias geriátricas efectivas para el tratamiento del linfoma no Hodgkin mortal: conclusiones de un estudio de caso.

This case report delves into the intricate medical history of an 85-year-old male who experienced a myriad of health challenges throughout his years. With a medical history full of conditions, such as stroke, sinus bradycardia, chronic obstructive pulmonary disease, severe pulmonary hypertension, and chronic gastritis, the patient´s health profile is further complicated by prostatic hypertrophy, persistent dorsalgia and lumbalgia, the presence of a thyroid nodule, and a recent onset of hypothyroidism. Among the diverse medical conditions of this patient, our narrative is primarily centered on his latest diagnosis: non-Hodgkin´s lymphoma. Non-Hodgkin´s lymphoma is not just a mere addition to his already complex medical history; it is a malignant neoplasm that shapes worldwide patterns of cancer mortality. The first indicators that led to this discovery were the patient´s complaints of persistent pain in the left lateral neck region associated with dysphagia. This was not an isolated symptom; the patient also reported a month-long history of asthenia, myalgias, weakness around the pelvic girdle, fatigue, and hyporexia, depicting a concerning clinical picture. Advanced diagnostic tools, namely ultrasound and computed tomography, shed light on submaxillary and cervical adenopathies. To corroborate such findings and get a definitive diagnosis of malignancy, a fine-needle aspiration was advised. Through this case, we aim not only to describe a clinical scenario but to highlight the challenges involved in the diagnosing and treatment of non-Hodgkin ´s lymphoma, especially in elderly patients. The overlap of multiple comorbidities adds further complexity to the scene, demanding meticulous care and expertise. This report serves as an educational tool for oncology experts, as well as testimony to the complexities of patient care in the oncology diagnostic and treatment setting.

Este reporte de caso se centra en el intricado historial médico de un varon de 85 años que experimenta una miriada de problemas de salud a lo largo de sus años. Con un historial médico lleno de afecciones, como accidente cerebrovascular, bradicardia sinusal, enfermedad pulmonar obstructiva crónica, hipertensión pulmonar grave y gastritis crónica, el perfil de salud del paciente se complica aún más por la presencia de hipertrofia prostática, dorsalgia y lumbalgia persistentes, la presencia de un nódulo tiroideo y el reciente diagnóstico de hipotiroidismo. Entre las diversas afecciones de este paciente, nuestra narración se centra principalmente en su último diagnóstico: linfoma no Hodgkin. El linfoma no hodgkiniano no es un mero añadido a su ya complejo historial médico; es una neoplasia maligna que configura las tendencias de mortalidad por cáncer a nivel mundial. Los primeros indicadores que llevaron a este descubrimiento fueron las quejas del paciente por dolor persistente en la región lateral izquierda del cuello, asociado a disfagia. No se trataba de un síntoma aislado, ya que el paciente también refería desde hacía un mes astenia, mialgias, debilidad alrededor de la cintura pélvica, fatiga e hiporexia, lo que describía un cuadro clínico preocupante. Las herramientas diagnósticas avanzadas, a saber, la ecografía y la tomografía computarizada, arrojaron luz sobre las adenopatías submaxilares y cervicales. revelaron sobre las adenopatías submaxilares y cervicales.

Current landscape of CD3 bispecific antibodies in hematologic malignancies.

Over the past 30 years the incorporation of monoclonal antibody (mAb) treatments into the management of hematologic malignancies has led to significant improvements in patient outcomes. The key limitation of mAb treatments is the necessity for target antigen presentation on major histocompatibility complex (MHC) and costimulatory molecules to elicit a cytotoxic immune response. With the advent of bispecific antibodies (BsAbs), these limitations can be overcome through direct stimulation of cytotoxic T cells, thus limiting tumor cell evasion. BsAbs are rapidly being incorporated into treatment regimens for hematologic malignancies, and there are now seven FDA-approved treatments in this class, six of which have been approved in the past year. In this review we describe the function, complications, and clinical trial data available for CD3 BsAbs in the treatment of lymphoma, myeloma, and leukemia.

Exploring the Health Benefits of Boletus aereus Polysaccharides: Extraction, Structural Characterization, and Antiproliferative Properties against Non-Hodgkin's Lymphomas (NHLs).

Boletus aereus Fr. ex Bull. stands out as a delectable edible mushroom with high nutritional and medicinal values, featuring polysaccharides as its primary nutrient composition. In our continuous exploration of its beneficial substances, a novel polysaccharide (BAPN-1) with a molecular weight of 2279 kDa was prepared. It was identified as a glucan with a backbone composed of the residues →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1→ connected in a proportion of 5:1 and a ß-Glcp-(1→ side residue attached at C6 of the →4,6)-α-Glcp-(1→ residue. Biologically, BAPN-1 exhibited broad-spectrum antiproliferative activities against various NHL cells, including HuT-78, OCI-LY1, OCI-LY18, Jurkat, RL, and Karpas-299, with IC50 values of 0.73, 1.21, 3.18, 1.52, 3.34, and 4.25 mg/mL, respectively. Additionally, BAPN-1 significantly induced cell cycle arrest in the G2/M phase and caused apoptosis of NHL cells. Mechanistically, bulk RNA sequencing and Western blot analysis revealed that BAPN-1 could upregulate cyclin B1 and enhance cleaved caspase-9 expression through the inhibition of FGFR3 and RAF-MEK-ERK signaling pathways. This work supports the improved utilization of B. aereus in high-value health products.

Prognostic Significance of Bcl-2 Expression in Non-germinal Center B-cell-Like Diffuse Large B-cell Lymphoma.

INTRODUCTION: Diffuse large B-cell lymphomas (DLBCLs) are a group of malignant neoplasms with extensive clinical and molecular heterogeneity. Several key genetic aberrations have been identified, such as those involving the MYC, BCL6, and BCL2 genes. Prior studies on the prognostic significance of Bcl-2 protein expression in DLBCL have been contradictory, with some suggesting it has an adverse effect, while others have shown no such association. Bcl-2 is known to be more highly expressed in the non-germinal center B-cell-like (non-GCB) subtype compared to germinal center B-cell-like (GCB) DLBCL. Non-GCB status is associated with a less favorable prognosis. This study aimed to investigate whether the expression of Bcl-2 protein in non-GCB DLBCL influences response to treatment, progression-free survival, or overall survival. METHODS: In this retrospective study, we investigated whether there was a difference in the clinical outcomes of non-GCB DLBCL cases (n = 97) that were confirmed by immunochemistry to demonstrate high levels of Bcl-2 protein expression (>50% neoplastic cells stained) when compared to those who were deemed negative based on this criterion. Response to rituximab-based induction immunochemotherapy, five-year progression-free survival, and five-year overall survival were assessed. RESULTS: There was no statistically significant difference in response to treatment, five-year progression-free survival, or five-year overall survival between the patients who were positive for Bcl-2 (n = 70) compared to those who were considered Bcl-2 negative (n = 27). CONCLUSION: High levels of Bcl-2 protein expression do not appear to be of prognostic significance in non-GCB DLBCL and therefore Bcl-2 may not be a key therapeutic target in the treatment and improvement of clinical outcome in such cases.

Exploring risk factors for autoimmune diseases complicated by non-hodgkin lymphoma through regulatory T cell immune-related traits: a Mendelian randomization study.

Background: The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) immune traits and ADs complicated by NHL remains debated. Methods: Aggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren's syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn's disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships. Results: There was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings. Conclusions: There existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.

The causality between gut microbiota and non-Hodgkin lymphoma: a two-sample bidirectional Mendelian randomization study.

Background: Studies have indicated an association between gut microbiota (GM) and non-Hodgkin lymphoma (NHL). However, the causality between GM and NHL remains unclear. This study aims to investigate the causality between GM and NHL using Mendelian randomization (MR). Methods: Data on GM is sourced from the MiBioGen consortium, while data on NHL and its subtypes is sourced from the FinnGen consortium R10 version. Inverse variance weighted (IVW) was employed for the primary MR analysis method, with methods such as Bayesian weighted Mendelian randomisation (BWMR) as an adjunct. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO, and the "Leave-one-out" method. Results: The MR results showed that there is a causality between 27 GMs and NHL. Among them, 20 were negatively associated (OR < 1), and 7 were positively associated (OR > 1) with the corresponding diseases. All 27 MR results passed sensitivity tests, and there was no reverse causal association. Conclusion: By demonstrating a causal link between GM and NHL, this research offers novel ideas to prevent, monitor, and cure NHL later.

The causal effect of adipose tissue on Hodgkin's lymphoma: two-sample Mendelian randomization study and validation.

Background: Extensive research has been conducted on the correlation between adipose tissue and the risk of malignant lymphoma. Despite numerous observational studies exploring this connection, uncertainty remains regarding a causal relationship between adipose tissue and malignant lymphoma. Methods: The increase or decrease in adipose tissue was represented by the height of BMI. The BMI and malignant lymphoma genome-wide association studies (GWAS) used a summary dataset from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) that met the criteria of P <5e-8 and LD of r2 = 0.001 in the BMI GWAS were chosen as genetic instrumental variants (IVs). Proxy SNPs with LD of r2 > 0.8 were identified, while palindromic and outlier SNPs were excluded. Mendelian randomization (MR) analysis used five methods, including inverse-variance weighted (IVW) model, weighted median (WM), MR-Egger, simple mode, and weighted mode. Sensitivity assessments included Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis. Participants randomly selected by the National Center for Health Statistics (NHANSE) and newly diagnosed HL patients at Fujian Medical University Union Hospital were used for external validation. Results: The results of the MR analysis strongly supported the causal link between BMI and Hodgkin's lymphoma (HL). The research demonstrated that individuals with lower BMI face a significantly increased risk of developing HL, with a 91.65% higher risk (ORIVW = 0.0835, 95% CI 0.0147 - 0.4733, P = 0.005). No signs of horizontal or directional pleiotropy were observed in the MR studies. The validation results aligned with the results from the MR analysis (OR = 0.871, 95% CI 0.826 - 0.918, P< 0.001). And there was no causal relationship between BMI and non-Hodgkin's lymphoma (NHL). Conclusions: The MR analysis study demonstrated a direct correlation between lower BMI and HL. This suggested that a decrease in adipose tissue increases the risk of developing HL. Nevertheless, further research is essential to grasp the underlying mechanism of this causal association comprehensively.

Enhancing lymphoma diagnosis on core needle biopsies: Integrating immunohistochemistry with flow cytometry.

Image-guided core needle biopsies (IG-CNB) represent a minimally invasive approach for obtaining tissue in patients with lymphadenopathy and suspected lymphoma. Despite their utility, diagnostic challenges persist, with lower efficacy compared with excisional biopsies. Our study aimed to evaluate the potential utility of incorporation of flow cytometry (FC) alongside immunohistochemistry (IHC) when performing IG-CNB for suspected lymphoproliferative diseases. Analyzing 170 consecutive cases, guided by ultrasound (n = 94) or computer tomography (n = 76), we employed a diagnostic algorithm, already established in our laboratory practice, utilizing three antibody cocktail-equipped tubes tailored for defining lymphomas, particularly those of B-cell origin. FC expedited the diagnostic process, yielding presumptive results in 87.6% of cases within 48 h, with a positive predictive value of 98%. Addition of FC to routine IHC enhanced the diagnostic rate from 91.2% to 95.3%, reducing IG-CNB failure rate by 45%, from 8.8% to 4.7%. This enhancement was particularly notable for deep-seated sites and in the setting of suspected disease recurrences. Consequently, FC emerges as a valuable adjunctive tool, allowing for the improvement of diagnostic performance, with a particular focus on the ability to quantify the expression of surface markers for targeted therapies, and holding the potential to diminish the necessity for repeat excisional biopsies subsequent to IG-CNB procedures.

[A Retrospective Study of R±DHAX Regimen versus R-CHOP Regimen First-Line Treatment of Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed, and they were divided into rituximab±DHAX (R±DHAX) regimen group (18 cases) and rituximab±CHOP (R-CHOP) regimen group (18 cases) according to the treatment plan, and clinical features, efficacy and survival of the patients were observed. RESULTS: Compared with R-CHOP group, patients of the R±DHAX group were older, and had worse performance status and higher IPI score, the differences between two groups in age, ECOG score and IPI score were statistically significant ( P =0.005 P =0.018, P =0.035), but there were no significant differences beween two groups in gender, whether there were B symptoms, whether LDH was elevated, whether there was extranodal involvement, cell origin, bone marrow infiltration, and whether rituximab was combined ( P =0.738, P =1, P =0.315, P =0.305, P =0.413, P =0.177, P =0.711, P =0.229). The efficacy could be evaluated in 36 cases, including CR 14 (38.9%), PR 17 (47.2%), PD 5 (13.9%), and ORR of 86.1% (31/36). There were no statistically significant differences in CRï¼»(27.8%（5/18） vs 50.0%（9/18）; P >0.05ï¼½ and PR ï¼»44.4%（8/18） vs 50.0%（9/18）; P >0.05ï¼½ of R±DHAX group and R-CHOP group, there was statistically significant difference in ORRï¼»72.2%（13/18） vs 100.0%（18/18）; P =0.045ï¼½ between two groups. The 1-year OS of R±DHAX group and R-CHOP group was (38.9±11.5%)% and (94.4±7.4%)%, respectively, 2-year OS was (16.7±8.8)% and (72.2±10.6)%, respectively, and the differences between two groups were statistically significant ( P =0.001, P =0.002). The median survival time in the R±DHAX group was 11 months(95%CI :8.9-13.1), and the median survival time in the R-CHOP group was not reached, and there was a statistically significant difference between the groups (P < 0.001). CONCLUSION: For elderly DLBCL patients, R±DHAX may not be superior to R-CHOP in OS, and ECOG score, IPI score and age may affect the survival of elderly DLBCL patients. However, R±DHAX regimen is safe, tolerable and has a certain efficacy, which can be used as one of the clinical treatment options for elderly DLBCL.

[Research Progress of CAR-T Cell Immunotherapy in B-Cell Non-Hodgkin's Lymphoma--Review].

Chimeric antigen receptor T (CAR-T) cell therapy is a rapidly developing new immunotherapy in recent years. Compared with other therapies, CAR-T has significant advantages for high-risk and relapsed/refractory B cell non-Hodgkin's lymphoma (B-NHL) patients. Currently, a variety of anti-CD19 CAR-T cells have been approved by the FDA for the treatment of B-NHL, such as axicabtagene ciloleucel, tisagenlecucel, lisocababtagene maraleucel and brexucabtagene autoleucel. In addition, many studies are actively exploring and developing different targeted CAR-T cells, which show great potential in B-NHL. This review briefly summarized the latest research progress on the application of CAR-T in common B-NHL.

Delayed Traumatic Rupture of the Spleen in a Patient with Mantle Cell Non-Hodgkin Lymphoma after an In-Hospital Fall: A Fatal Case.

Splenic rupture and hematoma are significant complications that can occur in patients with non-Hodgkin lymphoma (NHL). Understanding these associated complications is essential for optimal patient management and enhanced patient outcomes. Histopathological and immunohistochemical analyses are crucial in diagnosing NHL and assessing splenic involvement. In this study, a judicial autopsy had been requested by the Prosecutor's Office for a malpractice claim due to a fall in the hospital. In the Emergency Department, a 72-year-old man fell from a gurney and reported sustaining a wound to his forehead. No other symptoms were reported. A face and brain CT scan showed no abnormalities. Nine days after discharge, the patient presented with abdominal pain. An abdominal CT revealed splenic rupture and hemoperitoneum. The patient underwent open splenectomy but showed signs of hemodynamic shock and subsequently died. The evidence from the autopsy allowed us to diagnose mantle cell non-Hodgkin lymphoma with spleen involvement, previously unknown. Histopathological and immunohistochemical analyses were performed to assess the diagnosis of splenic rupture and estimate its timing. The findings strongly suggest that the splenic rupture was associated with the patient's fall and the pre-existing malignancy. This case highlights the importance of considering an underlying hematological malignancy when investigating delayed splenic rupture. An immunohistochemical study of spleen samples allowed the timing of splenic hematoma and rupture to be assessed, leading to the establishment of a causal relationship with trauma.

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.

End points in clinical trials in diffuse large B-cell lymphoma: time for more dialogue?

We observed lack of clarity and consistency in end point definitions of large randomized clinical trials in diffuse large B-cell lymphoma. These inconsistencies are such that trials might, in fact, address different clinical questions. They complicate interpretation of results, including comparisons across studies. Problems arise from different ways to account for events occurring after randomization including absence of improvement in disease status, treatment discontinuation or the initiation of new therapy. We call for more dialogue between stakeholders to define with clarity the questions of interest and corresponding end points. We illustrate that assessing different end point rules across a range of plausible patient journeys can be a powerful tool to facilitate such a discussion and contribute to better understanding of patient-relevant end points.

What is this article about? This article talks about the lack of clarity and consistency in the definitions of outcomes used in clinical trials that investigate new treatments for diffuse large B-cell lymphoma. This is mainly due to how these different outcome definitions handle events such as absence of improvement in disease status, treatment discontinuation or initiation of new treatment. The authors discuss how these inconsistencies make it hard to interpret the results of individual clinical trials and to compare results across clinical trials.Why is it important? Defining the above events and consequently defining outcomes affects what we can learn from the trials and can lead to different results. Some approaches may not reflect good and bad outcomes for patients appropriately. This makes it challenging for patients, physicians, health authorities and payors to understand the true benefit of treatments under investigation and which one is better.What are the key take-aways? This article serves as a call-to-action for more dialogue among all stakeholders involved in drug development and the decision-making process related to drug evaluations. There is an urgent need for clinical trials to be designed with more clarity and consistency on what is being measured so that relevant questions for patients and prescribing physicians are addressed. Understanding patient journeys will be key to successfully understand what truly matters to patients and how to measure the benefit of new treatments. Such discussions will contribute toward more clarity and consistency in the evaluation of new treatments.

Cardiac Tamponade: An Initial Manifestation of Diffuse Large B Cell Lymphoma.

Pericardial effusion, a clinical condition characterized by an abnormal accumulation of fluid in the pericardial cavity, has multiple etiological factors. One of the prominent causes is malignant effusion. The patient is a 69-year-old female with a past medical history of Crohn's disease, melanoma status post-resection, and osteoarthritis. She presented with complaints of abdominal discomfort, shortness of breath on exertion, and lower extremity swelling for the past 2-3 days. She was recently discharged four days before this visit after being treated for a viral infection. A physical examination was significant for tachycardia, muffled heart sounds, abdominal distention, and bilateral lower extremity swelling. Labs were in the normal range except for elevated liver enzymes and sodium of 130 mmol/L. A chest X-ray revealed a small bilateral effusion; a bedside echocardiogram showed an ejection fraction greater than 70% and a large pericardial effusion >2 cm, consistent with cardiac tamponade. Emergent pericardiocentesis was performed with the drainage of 250 milliliters of hemorrhagic fluid, which was sent for diagnostic studies. Post-procedure echo on the next day showed an EF of 35-40% and no recurrent pericardial effusion. The workup for connective tissue disease was negative except for elevated antinuclear antibodies (ANA). CT of the abdomen and pelvis revealed gastric wall thickening with no solid organ mass. Her pericardial fluid studies were consistent with exudative etiology and positive for atypical lymphoid cells, leading to the diagnosis of diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Malignant pericardial effusion is common due to solid organ malignancy; however, it is rare with diffuse large B cell lymphoma (DLBCL). We present an intriguing case where pericardial effusion was the precursor to the eventual diagnosis of DLBCL, highlighting the complexity and diverse manifestations of this lymphoma subtype.

Global spatiotemporal distributions of lymphoma from 1990 to 2019: A Joinpoint regression analysis based on the global burden of disease study 2019, and projections until 2044.

Lymphoma is a dissimilar collection of malignant neoplasms arising from the clonal propagation of lymphocytes. It is conventionally classified into two categories: Hodgkin lymphoma and non-Hodgkin lymphoma. The purpose of this study is to analyze the temporal patterns in the incidence of lymphoma worldwide over the past few decades and forecast the future trends from 2020 to 2044. Data on HL and NHL were obtained from the Global Burden of Disease Study 2019. In an effort to estimate the incidence rate trend, the Joinpoint regression analysis model was exploited. What's more, to project the disease burden by 2044, the Bayesian age-period-cohort analysis was employed. In 2019, higher incidence rates were observed in males and the elderly for both subtypes. Over the last three decades, a significant decline in the age-standardized incidence rate of HL was observed, while NHL has shown an increasing trend. By 2044, the age-standardized incidence rate of HL is anticipated to decrease in males and increase in females, while that of NHL is expected to rise. This study presents a new assessment of the spatiotemporal distributions of lymphoma. Significant emphasis should be placed on the effective management and long-term monitoring of patients to mitigate the potential future impact of the disease.