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Background: The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin's lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale. Methods: Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10. Results: Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling (n = 14), fatigue (n = 11), and pain (n = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms. Conclusions: This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL. [ABSTRACT FROM AUTHOR]

Background: Voriconazole is primarily metabolized by CYP2C19 and CYP3A4. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted voriconazole concentrations. Case summary: In this case report, we describe the case of a 64-year-old man who was treated for non-Hodgkin's lymphoma with continuous glucocorticoids co-administrated with voriconazole against invasive pulmonary aspergillosis. A decrease in trough concentration (Cmin) of voriconazole was observed and related with co-administration of dexamethasone in the patient carrying the CYP2C19 *1*2 genotype: voriconazole Cmin/dose ratios of 0.018 (0.1 mg L-1 / 5.7 mg kg-1 day-1), 0.18 (1 mg L-1/5.7 mg kg-1 day-1), and 0.23 (2 mg L-1 / 8.6 mg kg-1 day-1) at dexamethasone doses of 20, 12.5, and 2.5 mg, respectively. Sub-therapeutic voriconazole Cmin was associated with high- and moderate-dose dexamethasone (20 and 12.5 mg), leading to failure of antifungal treatment. Conclusion: The extent of voriconazole-dexamethasone interaction was determined by the dose of dexamethasone and associated with the CYP2C19 *1*2 genotype. Therapeutic drug monitoring of voriconazole is necessary to avoid clinically relevant interactions for optimal antifungal therapy. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a type of non-Hodgkin lymphoma that involves the brain, spinal cord, and eyes. It is a rare, aggressive tumor that can affect immunocompetent or immunocompromised patients. Immunodeficiency states are a risk factor for developing PCNSL. The gold standard method to confirm the diagnosis is a stereotactic brain biopsy. Given the rarity and acuity of the disease, management recommendations are based on a few prospective trials and retrospective studies. It is a chemosensitive malignancy; however, half of the respondents will relapse with a dismal prognosis. The adoption of high-dose methotrexate, rituximab, and consolidation strategies has significantly improved outcomes. The prognosis has improved over the past decade, but it remains dismal for the elderly. Targeted therapies and immunotherapies may have promising results. This review article summarizes the clinical presentation, evaluation, and management of patients with PCNSL and shed some light on the future advances in this disease. [ABSTRACT FROM AUTHOR]

The relevance of this study arises from the pressing need for a deeper investigation into the morphological aspects of identifying focal and localised lesions in the spleen. The spleen performs several vital functions, including immune, haematological, storage, metabolic, haemostatic, hormonal, and antiblastic roles, among others. Therefore, this study aimed to determine the clinical characteristics of splenic tumour lesions and their structural changes, as well as to identify the macroscopic appearance of the organ post-splenectomy. In diagnosing splenic diseases, a key instrumental method was employed - ultrasound examination with Doppler imaging - which enabled comprehensive investigation, analysis, and characterisation of parenchymal pathologies. Animals underwent clinical examinations during routine health checks or upon presentation of symptoms. When a splenic neoplasm was detected, surgical treatment was carried out, specifically through an open laparotomy and splenectomy. The surgery was performed under combined general anaesthesia (using both non-inhalational and inhalational anaesthetics). The intraoperatively collected material from the affected organ was subjected to histological examination. It was found that the pathomorphosis of splenic lesions varies, and the author's pathological and histological studies highlight the key morphological characteristics of the neoplasms. Accordingly, any splenic neoplasm can pose a life-threatening condition for several reasons: organ rupture and haemorrhage, organ torsion, and malignancy, among others. The findings are crucial for verifying splenic pathology, enabling the establishment of a definitive clinical diagnosis, facilitating treatment of the animal, and extending its lifespan. The practical significance of the results lies in identifying the need for comprehensive clinical and morphological investigations in diagnosing splenic diseases, as well as examining histological preparations for cellular and tissue changes. In veterinary medicine, the method of surgical treatment for splenic lesions in animals may be a subject of debate. In contrast, in human medicine, established protocols exist for performing organ-destructive operations such as splenectomy (by open or laparoscopic approach), organ-preserving procedures like splenic resection or splenectomy with autotransplantation of splenic tissue into the greater omentum (by open or laparoscopic approach), and percutaneous punctures for splenic cysts. [ABSTRACT FROM AUTHOR]

Primary vitreoretinal lymphoma (PVRL) is a rare sub entity of the primary central nervous system lymphoma affecting the intraocular compartment without brain involvement at the time of diagnosis. The severity of the disease results mainly from the high risk of brain relapse or progression in addition to the risk of permanent vision loss. The diagnosis remains a major challenge due to the scarcity and the fragility of lymphoma cells in the vitreous and requires a close coordination between pathologist and ophthalmologist. Multimodal imaging, interleukin levels and molecular biology are major diagnostic tools if no lymphoma cell can be identified after vitrectomy. Treatments are extremely heterogenous because of the lack of robust prospective studies. Therapeutic options are based on multiple retrospective and small cohort trials. In first line settings, local treatments with intravitreal injection of méthotrexate or ocular radiotherapy, systemic treatment based on chemotherapy with high dose méthotrexate or a combination of both can be used. At relapse, intensive chemotherapy with autologous stem cell transplant can be considered if the patient is eligible. Single-agent therapies such as lénalidomide, témozolomide or Bruton tyrosine kinase inhibitors are effective at relapse and are starting to be tested in first-line treatment. Response assessment is still based on clinical examination. The role of interleukin level, a promising biomarker, needs to be confirmed for diagnosis and monitoring of the therapeutic response. The French national LOC network issued guidelines based on the available data from the literature, aiming to homogenize the care of PVRL patients. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a subtype of B-cell lymphoma derived from CD5-positive antigen-naïve pre-germinal center B-cells within the mantle zone that surrounds normal germinal center follicles. MCL comprises approximately 5 to 10% of all lymphomas. Tonsil is the most common location of MCL in the head and neck region, followed by the nasopharynx. Primary MCL involving the nasopharynx is extremely rare. Its clinical course is very aggressive with frequent relapses after conventional chemotherapy. It always presents as a protruding mass on the mucosal lining of the pharyngeal cavity. Here, we report a new nodular type of MCL in the nasopharynx. Endoscopically, this case showed multiple nodular lesions of primary MCL on the nasopharyngeal mucosa. This unique finding has not been reported yet in the English literature. These lesions should be differentiated from simple pharyngeal infections or benign lymphoid hyperplasia in the nasopharynx. [ABSTRACT FROM AUTHOR]

Summary: We reviewed cases with aggressive B‐cell non‐Hodgkin lymphoma who relapsed or progressed following glofitamab. The prognosis was poor, with low rates of response to subsequent salvage therapies, and a median overall survival of 4.1 months from the time of progression. There were high rates of CD20 loss (59%) at the time of relapse. In a field where CD20 × CD3 bispecific antibodies are entering routine clinical use, our experience highlights a potential means of resistance. It illustrates both the need to further characterise mechanisms of CD20 loss, and to pursue clinical trials of novel non‐CD20‐directed treatments in this cohort. [ABSTRACT FROM AUTHOR]

Summary: Infection and lymphopenia are established bendamustine‐related complications. The relationship between lymphopenia severity and infection risk, and the role of antimicrobial prophylaxis, is not well described. This multicentre retrospective study analysed infection characteristics and antimicrobial prophylaxis in 302 bendamustine‐treated indolent non‐Hodgkin lymphoma patients. Lymphopenia (<1 × 109/L) was near universal and time to lymphocyte recovery correlated with cumulative bendamustine dose. No association between lymphopenia severity and duration with infection was observed. Infections occurred in 44% of patients (50% bacterial) with 27% hospitalised; 32% of infections occurred ≥3 months post bendamustine completion. Infection was associated with obinutuzumab and/or maintenance anti‐CD20 therapy, prior therapy and advanced stage. Twenty‐four opportunistic infections occurred in 21 patients: ten varicella zoster virus (VZV), seven herpes simplex virus (HSV), one cytomegalovirus, one progressive multifocal leucoencephalopathy, one nocardiosis, one Pneumocystis jiroveci pneumonia (PJP) and three other fungal infections. VZV/HSV and PJP prophylaxis were prescribed to 42% and 54% respectively. Fewer VZV/HSV infections occurred in patients receiving prophylaxis (HR 0.14, p = 0.061) while PJP prophylaxis was associated with reduced risk of bacterial infection (HR 0.48, p = 0.004). Our study demonstrates a significant infection risk regardless of lymphopenia severity and supports prophylaxis to mitigate the risk of early and delayed infections. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS), a chronic autoimmune condition, has been associated with an increased risk of several cancers. This study aims to delve into the relationship between pSS and the potential development of non-Hodgkin's lymphoma (NHL) utilizing an in-depth systematic review and meta-analysis approach. To thoroughly explore the topic, we conducted a thorough examination of the literature, drawing from reputable databases such as ProQuest, PubMed, Web of Science, Cochrane, and Google Scholar. Our data collection spanned until February 8, 2024, with no time limitation. Data were analyzed with Stata 14 software at a significance threshold of p < 0.05. We examined 15 cohort studies encompassing a total of 50,308 individuals from 1997 to 2023. The findings revealed a substantial link between pSS and the risk of NHL, evident across all demographics. Specifically, the standardized incidence ratio (SIR) was generally 8.78 (95% CI 5.51, 13.99), with similar trends observed in both men (SIR, 6.29; 95% CI 1.93, 20.51) and women (SIR, 9.60; 95% CI 5.89, 15.63). Additionally, the SIR (10.50 (95% CI 7, 15.75)), HR (2.82 (95% CI 1.28, 6.18)), and OR (10.50 (95% CI 3.04, 36.28)) indices further supported this association. Furthermore, the risk of non-NHL associated with pSS was noticeable across different age groups of 40–49 years (SIR, 30.13; 95% CI 14.62, 62.08), 50–59 years (SIR, 9.12; 95% CI 5.13, 16.19), and 60–69 years (SIR, 9; 95% CI 4.68, 17.32). pSS substantively augments the likelihood of NHL manifestation. It notably impacts females and those in earlier stages of adulthood with more acuity than males and older cohorts. [ABSTRACT FROM AUTHOR]

Simple Summary: Autoantibodies against the metabotropic glutamate receptor 5 (mGluR5) have been linked to Ophelia syndrome, a combination of limbic encephalitis and Hodgkin lymphoma (HL). We studied mGluR5 expression in 57 pediatric HL and NHL by immunohistochemistry to explore the relationship between mGluR5 antibody formation and HL. All lymphoma tissues displayed mGluR5 staining, especially HL Reed–Sternberg cells. There was no staining in age-matched healthy lymph nodes, and we did not find GRM5 transcripts in RNA-sequencing data from normal lymphocytes. Lower mGluR5 levels in HL correlated with younger patients and EBV-positive tumors. Cases of paraneoplastic and neurological symptoms were found exclusively in the HL cohort. The frequent presence of mGluR5 in lymphoma tissue suggests a possible role in tumor development. This finding is in line with reports that glutamatergic signaling affects the outcome in other cancers. However, further studies in larger cohorts are needed to evaluate the impact of mGluR5 on HL severity. Autoantibodies targeting the neuronal antigen metabotropic glutamate receptor 5 (mGluR5) have been identified in patients with Ophelia syndrome, which describes a co-occurrence of paraneoplastic limbic encephalitis and Hodgkin lymphoma (HL). Little data exist regarding frequency and function of mGluR5 in HL and its potential role in causing seropositive paraneoplastic disease. We studied a representative cohort of pediatric HL and NHL patients (n = 57) using immunohistochemistry and fluorescence staining to investigate mGluR5 expression. All lymphoma tissues displayed positive mGluR5 staining, with focus on Hodgkin–Reed–Sternberg (H-RS) cells. We did not detect any mGluR5 staining in tumor-free lymph nodes, which is consistent with the absence of GRM5 transcripts in RNA-sequencing data from non-malignant B and T cells. The frequent presence in pediatric lymphoma falls in line with reports of mGluR5 expression and associated tumor progression in other malignancies. We tested for correlation with clinical features, focusing on disease progression and neurological symptoms. Low mGluR5 expression in H-RS cells correlated with young patient age (<15 years) and positive histology for EBV infection. Paraneoplastic or neurological symptoms were found exclusively in HL patients. While an impact of mGluR5 on HL severity remains possible, a prognostic value of mGluR5 expression levels requires further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study, we investigated immune regulation in a subtype of lymphoma called mantle cell lymphoma (MCL). Our goal was to understand how different types of immune cells, specifically T cells, behave in MCL. To do this, we combined image analysis and a technology called digital spatial profiling. We looked at tumor tissue from 102 MCL patients and analyzed different T-cell subsets. Interestingly, we found that late-stage differentiated T cells (CD57+) were more common in tumor-rich areas. These T cells also showed an increased expression of immune suppressive markers. We identified potential targets for treatment, such as CD47, IDO1, and CTLA-4. Additionally, we found that patients with sparse T-cell infiltration had an increased amount of GITR, which tentatively can be therapeutically targeted. Our findings shed light on previously unknown features of T-cell behavior in MCL. With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57−) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TC and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ TC-cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL. [ABSTRACT FROM AUTHOR]

Breast lymphomas are rare, malignant breast neoplasms with a heterogeneous pattern of clinical symptoms. Burkitt's lymphoma is a rare, highly aggressive, and rapidly growing B-cell non-Hodgkin lymphoma. We report about a 27-year-old woman diagnosed as having secondary breast Burkitt's lymphoma, probably originating from the stomach, with multiple distant metastases. Breast ultrasonography revealed multiple, variable sized, heterogeneous masses with posterior acoustic enhancement and echogenic rims. These imaging findings may sometimes overlap with those of other breast malignancies. However, unlike other breast malignancies, lymphoma can be diagnosed by biopsy and does not require surgical excision. To avoid unnecessary treatment, radiologists and clinicians should be aware of the characteristic imaging features of breast lymphomas. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B cell lymphoma (DLBCL) within non-Hodgkin lymphoma has several morphologic and clinicopathologic variants. DLBCL has two prognostically important subtypes, germinal center B cell (GCB) and nongerminal center (Non-GCB) with the non-GCB having an inferior outcome. Immunohistochemical co-expression of cellular myelocytomatosis (CMYC) and BCL2 in DLBCL has poor prognosis and is considered as double-expressor lymphoma (DEL). Aims and Objectives: This study was done to identify DEL using immunohistochemistry among GCB and non-GCB DLBCL and to assess their treatment response. Methods and Material: A retrospective analysis of 97 DLBCL cases received in our department was done. Formalin-fixed paraffin blocks were used to prepare Hematoxylin and eosin-stained sections, immunohistochemical subtyping (into GCB and non-GCB using CD10, BCL6, and MUM1) and further to identify DEL (using CMYC and BCL2). Statistical Analysis: Analysis was done using Chi-square test (Statistical Package for Social Sciences version 18), and P <.05 was considered significant. Kaplan-Meier test was used to estimate overall survival. Results: Of the total 97 DLBCL cases analyzed, 33 (34%) were DEL and 64 (66%) were non-DEL. Of the DEL, 13 (13.40%) were GCB subtype and 20 (20.6%) were non-GCB. However, there was no statistically significant difference in the overall survival and treatment response between DEL and non-DEL. Conclusions: In this study, we found that DEL constituted about one-third of the total DLBCL and within the DEL non-GCB subtype was more common. Further studies should be performed in large population to study the difference in clinical outcome. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a rare, incurable, and aggressive B-cell non-Hodgkin lymphoma (NHL). Early MCL diagnosis and treatment is critical and puzzling due to inter/intra-tumoral heterogeneity and limited understanding of the underlying molecular mechanisms. We developed and applied a multifaceted analysis of selected publicly available transcriptomic data of well-defined MCL stages, integrating network-based methods for pathway enrichment analysis, co-expression module alignment, drug repurposing, and prediction of effective drug combinations. We demonstrate the "butterfly effect" emerging from a small set of initially differentially expressed genes, rapidly expanding into numerous deregulated cellular processes, signaling pathways, and core machineries as MCL becomes aggressive. We explore pathogenicity-related signaling circuits by detecting common co-expression modules in MCL stages, pointing out, among others, the role of VEGFA and SPARC proteins in MCL progression and recommend further study of precise drug combinations. Our findings highlight the benefit that can be leveraged by such an approach for better understanding pathobiology and identifying high-priority novel diagnostic and prognostic biomarkers, drug targets, and efficacious combination therapies against MCL that should be further validated for their clinical impact. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In the context of lymphoma, it is of paramount importance to perform subsequent Positron Emission Tomography‐Computed Tomography (PET‐CT) scans to ensure the comprehensive eradication of neoplasms. Primary renal diffuse tumors constitute less than 1% of all renal neoplasms. Among these, diffuse renal large B‐cell lymphoma is an exceedingly rare extranodal lymphoma. A 64‐year‐old male presented to the Department of Urology with complaints of persistent left flank discomfort for a duration of 2 weeks. Additionally, he reported generalized weakness, fatigue, and symptoms indicative of lower urinary tract obstruction, such as discomfort in the left testicle and dysuria. Ultrasound imaging revealed an echogenic structure with thickened, reactive walls and a turbid fluid core, located in the left flank, proximal to the lower pole of the kidney. This structure was subsequently identified as diffuse renal large B‐cell lymphoma. For the diagnosis of large B‐cell lymphomas, it is imperative that a proficient hematopathologist performs a comprehensive examination of the tumor tissue, preferably utilizing an excisional biopsy. The categorization of lymphoma requires specialized tests such as immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH), and molecular testing. In instances where a renal mass is detected, healthcare professionals should consider performing a biopsy. In lymphoma cases, follow‐up Positron Emission Tomography‐Computed Tomography (PET‐CT) scans are crucial to confirm the complete eradication of the tumor. [ABSTRACT FROM AUTHOR]

Background: Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma, characterized by abnormal B-cell growth within the germinal center. Research has shown the role of genes and molecular pathways in the pathogenesis of FL. However, the main factor of pathogenesis has not been determined. Therefore, in this study, the genes and molecular pathways related to the pathogenesis of FL were evaluated using a systems biology approach. Materials and Methods: In this study (bioinformatics analysis), the GSE32018 database was used for data analysis. This database was extracted from Gene Expression Omnibus (GEO). The sample of this database was 36, which included normal and FL samples. For this purpose, 23 cases were FL and 13 were healthy samples. Protein-protein interaction (PPI) is performed to show the interaction between DEGs. STRING software is used for this purpose. Associations between the hub genes, transcription factors, and microRNAs were assessed using the miRTarBase and TRRUST databases. The criteria used for data analysis included log fold change greater than one and p < 0.05. Results: After evaluating and analyzing the data, the results showed that 866 DEGs were identified between the control and FL samples. Of this population, 231 cases of UP regulation and 635 cases of downregulation were in FL samples compared to control samples. PPI network and hub gene analyses identified 7 hub genes, including RPL37A, MRPS7, RPS14, RPS28, RPL34, RPS20, and RPS3. According to the results, hsa-miR-191-5p has the highest interactions with hub genes among miRNAs, and KDM5A has the most interactions among TFs. Conclusion: Identifying genes and molecular pathways can be effective in designing therapeutic strategies and preventing the proliferation of FL cells, thereby increasing patients' survival. [ABSTRACT FROM AUTHOR]

Background and Objective: Inotuzumab ozogamicin is an antibody-drug conjugate approved for treating relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in adults. Pediatric pharmacokinetic data of inotuzumab ozogamicin are lacking. This study is the first to examine the population pharmacokinetics of inotuzumab ozogamicin in pediatric patients with relapsed/refractory BCP-ALL. Methods: From 531 adult patients with B-cell non-Hodgkin's lymphoma, 234 adult patients with BCP-ALL, and 53 pediatric patients with BCP-ALL, 8924 inotuzumab ozogamicin serum concentrations were analyzed using non-linear mixed-effects modeling. A published adult inotuzumab ozogamicin population-pharmacokinetic model, a two-compartment model with linear and time-dependent clearance, was adapted to describe the pediatric data. Results: Modifications in this analysis, compared to the published adult model, included: (i) re-estimating pharmacokinetic parameters and covariate effects; (ii) modifying covariate representation; and (iii) introducing relevant pediatric covariate effects (age on the decay coefficient of time-dependent clearance and ALL effect (disease type and/or different bioanalytical analysis methods) on initial values of time-dependent clearance). For patients with relapsed/refractory BCP-ALL, increasing age was associated with a decreasing decay coefficient of time-dependent clearance, reflecting that the target-mediated drug clearance declines more rapidly in children. In pediatric BCP-ALL, the median [interquartile range] cumulative area under the concentration–time curve was significantly higher among responders (n = 42) versus non-responders (n = 10) at the end of the first cycle (26.1 [18.9–35.0] vs 10.1 [9.19–16.1], × 103 ng*h/mL, p < 0.001). From simulations performed at the recommended pediatric phase II dose, inotuzumab ozogamicin exposure reached a similar level as observed in responding pediatric trial participants. Conclusions: The pharmacokinetic profile of inotuzumab ozogamicin in pediatric patients with relapsed/refractory BCP-ALL was well described in this study. No dose adjustment is required clinically for pediatric patients with BCP-ALL based on the simulated inotuzumab ozogamicin exposure at the recommended pediatric phase II dose, promising efficacy and acceptable tolerability. [ABSTRACT FROM AUTHOR]

• PEAM and BEAM demonstrated similar efficacy in terms of OS and TTR. • PEAM PEAM-conditioned patients had a shorter time to engraftment compared to BEAM, however, they received a higher CD34+ cell dose. • PEAM and BEAM regimes showed similar toxicity profiles, with a lower rate of nausea and mucositis in the PEAM arm. • The primary factors linked to poorer OS are pre-HSCT disease status (CR vs no-CR) and having undergone ≥4 lines of therapy prior to transplant. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard treatment for relapsed/refractory lymphoma patients. Yet, the widespread use of BEAM is hindered by carmustine accessibility. This study evaluates the efficacy and safety of PEAM (Cisplatin, Etoposide, Cytarabine, and Melphalan) versus BEAM in auto-HSCT for Hodgkin (HL) and non-Hodgkin lymphoma (NHL) patients. We conducted a retrospective single-center study of adult lymphoma patients who received PEAM or BEAM pretransplant conditioning between January 2004 to December 2022, comparing efficacy and safety outcomes. Among 143 patients (median age of 33 years, 58% males), 55 had HL, and 88 had NHL. The overall response rate (ORR) was 86.7% for PEAM and 72.3% for BEAM, and the relapse rate (RR) was lower for PEAM than BEAM (22.9% vs 45.6%). Median time to relapse (TTR) and overall survival (OS) were not reached for either group. PEAM exhibited a shorter time to both neutrophil (NE) and platelet (PE) engraftment compared to BEAM (10 vs 12 days), with a more tolerable gastrointestinal (GI) toxicity profile. Both BEAM and PEAM showed similar outcomes, demonstrating comparable efficacy in terms of ORR, TTR, and OS for both HL and NHL patients. However, PEAM-conditioning was associated with a shorter time to engraftment and fewer GI adverse events. [ABSTRACT FROM AUTHOR]

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Background: Childhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks. Objective: This population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring. Methods: Data on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers. Results: Offspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 – 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 – 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 – 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 – 1.54) before birth. Conclusions: In this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Follicular lymphoma (FL) is characterized by t(14;18)(q32;q21) involving the IGH and BCL2 genes. However, 10–15% of FLs lack the BCL2 rearrangement. These BCL2-rearrangement−negative FLs are clinically, pathologically, and genetically heterogeneous. The biological behavior and histological transformation of such FLs are not adequately characterized. Here, we report the first case of t(14;18)-negative FL that rapidly progressed to plasmablastic lymphoma (PBL). Case presentation: A previously healthy 51-year-old man presented with leg swelling. Computed tomography (CT) showed enlarged lymph nodes (LNs) throughout the body, including both inguinal areas. Needle biopsy of an inguinal LN suggested low-grade B-cell non-Hodgkin lymphoma. Excisional biopsy of a neck LN showed proliferation of centrocytic and centroblastic cells with follicular and diffuse growth patterns. Immunohistochemical analysis showed that the cells were positive for CD20, BCL6, CD10, and CD23. BCL2 staining was negative in the follicles and weak to moderately positive in the interfollicular areas. BCL2 fluorescence in situ hybridization result was negative. Targeted next-generation sequencing (NGS) revealed mutations in the TNFRSF14, CREBBP, STAT6, BCL6, CD79B, CD79A, and KLHL6 genes, without evidence of BCL2 or BCL6 rearrangement. The pathologic and genetic features were consistent with t(14;18)-negative FL. Two months after one cycle of bendamustine and rituximab chemotherapy, the patient developed left flank pain. Positron emission tomography/CT showed new development of a large hypermetabolic mass in the retroperitoneum. Needle biopsy of the retroperitoneal mass demonstrated diffuse proliferation of large plasmablastic cells, which were negative for the B-cell markers, BCL2, BCL6, and CD10; they were positive for MUM-1, CD138, CD38, and C-MYC. The pathologic findings were consistent with PBL. The clonal relationship between the initial FL and subsequent PBL was analyzed via targeted NGS. The tumors shared the same CREBBP, STAT6, BCL6, and CD79B mutations, strongly suggesting that the PBL had transformed from a FL clone. The PBL also harbored BRAF V600E mutation and IGH::MYC fusion in addition to IGH::IRF4 fusion. Conclusions: We propose that transformation or divergent clonal evolution of FL into PBL can occur when relevant genetic mutations are present. This study broadens the spectrum of histological transformation of t(14;18)-negative FL and emphasizes its biological and clinical heterogeneity. [ABSTRACT FROM AUTHOR]

Background: The short-term complications from chimeric antigen receptor Tcell therapy (CART) are well characterized, but the long-term complications still need to be further investigated. Therefore, herein, we will review the currently available literature published on the late adverse events following CART. Methods: We reviewed published data available from pivotal trials and real-world experiences with anti-CD19 CART (CART19) for adults with lymphoma. We defined late events as occurring or persisting beyond 1 month after CART infusion. We focused our literature review on the following late-event outcomes post-CART19: cytopenia, immune reconstitution, infections, and subsequent malignancies. Results: Grade 3-4 cytopenia beyond 30 days occurs in 30%-40% of patients and beyond 90 days in 3%-22% of patients and is usually managed with growth-factor and transfusion support, along with neutropenic prophylaxis. B-cell aplasia and hypogammaglobulinemia are expected on-target off-tumor effects of CART19, 44%-53% of patients have IgG < 400 mg/dL, and approximately 27%-38% of patients receive intravenous immunoglobulin (IVIG) replacement. Infections beyond the initial month from CART19 are not frequent and rarely severe, but they are more prevalent and severe when patients receive subsequent therapies post-CART19 for their underlying disease. Late neurotoxicity and neurocognitive impairment are uncommon, and other causes should be considered. T-cell lymphoma (TCL) after CART is an extremely rare event and not necessarily related to CAR transgene. Myeloid neoplasm is not rare post-CART, but unclear causality given heavily pretreated patient population is already at risk for therapy-related myeloid neoplasm. Conclusion: CART19 is associated with clinically significant long-term effects such as prolonged cytopenia, hypogammaglobulinemia, and infections that warrant clinical surveillance, but they are mostly manageable with a low risk of nonrelapse mortality. The risk of subsequent malignancies post-CART19 seems low, and the relationship with CART19 and/or prior therapies is unclear; but regardless of the possible causality, this should not impact the current benefit-risk ratio of CART19 for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Significant unmet need remains for patients with relapsed/refractory FL after =3 lines of prior therapy. While recent advancements have likely improved the survival of patients with FL, most patients will eventually relapse. The treatment of patients with FL after multiple relapses or those with refractory disease has historically led to lower overall response rates (ORR) and shorter progressionfree survival (PFS) with each subsequent line of therapy. New treatments with high ORR and durable PFS are needed in this setting, particularly in patients that progress within 2 years of first line chemoimmunotherapy (POD24) and/or those refractory chemoimmunotherapy. Chimeric antigen receptor T-cell therapies targeting the B-cell antigen CD-19 have shown to be an efficacious treatment option for both heavily pretreated patients and/or patients with refractory FL, resulting in a high ORR and durable remissions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Singlenucleotide 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), MREgger, 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. [ABSTRACT FROM AUTHOR]

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 MREgger, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Non-Hodgkin lymphoma (NHL) is a hematological malignancy that requires effective pharmacotherapy for optimal management. There is limited information regarding Yemeni clinicians' knowledge and practice of NHL pharmacotherapy. This study aims to assess the knowledge and practice of physicians and nurses in Yemen regarding pharmacotherapy of NHL. A cross-sectional study was conducted in Sana'a, Yemen, from January 1, 2022, to January 31, 2023. Two self-administrated and validated questionnaires were distributed to 99 physicians and 164 nurses involved in pharmacotherapy for NHL in different oncology centers and units across Yemen. Convenience samples were used to recruit participants. A binary logistic regression analysis was performed to identify factors associated with nurses' and physicians' knowledge and practice. The correlation coefficient was used to examine the relationship between knowledge and practice. A total of 77 physicians and 105 nurses completed the questionnaires. The results showed that 54.3% of nurses and 66.2% of physicians had poor knowledge of NHL pharmacotherapy. In terms of practice, 83.8% of nurses and 75.3% of physicians exhibited poor practice regarding NHL pharmacotherapy. Multivariable logistic regression analysis identified that nurses who received sufficient information about chemotherapy displayed a significant association with good knowledge, while nurses working in the chemotherapy administration department were significant predictors of good practice. Among physicians, those working in the National Oncology Center (NOC) in Sana'a demonstrated good practice. Correlation analysis revealed a positive relationship between nurses' knowledge and their practice. The study's results confirm deficiencies in knowledge and practice of pharmacotherapy for NHL among physicians and nurses in Yemen. Efforts should be made to enhance their understanding of treatment guidelines and to improve patient care. Improvement in educational programs and training opportunities may contribute to improving patient outcomes in the management of NHL. [ABSTRACT FROM AUTHOR]

Introduction: The management of metastatic spinal cord compression (mSCC) is a demanding task. The main challenges of mSCC include various manifestations and unpredictable outcomes with indiscriminate treatment recommendations. Because of attendant urgency with potentially devastating health consequences, the SCC is an emotionally disturbing experience whose management could take an impulsive rather than rational approach. The treatment strategy is particularly problematic when mSCC is caused by a malignant lymphoma with its protean attributes. Case Report: A 68-year-old female presented with generalized body pain and weight loss. Imaging studies revealed a vast bulk of the disease involving lymph nodes, spleen, visceral organs, musculature, marrow, and bones including vertebrae with extension into the spinal canal. A biopsy of the chest wall mass showed high-grade diffuse large B-cell lymphoma. A magnetic resonance imaging (MRI) of the spine demonstrated diffuse marrow replacement by the tumor of the thoracic and lumbar spine with compression of the cord. The prompt treatment with corticosteroids and immunochemotherapy (ICT) was recommended, but the patient elected to seek a second opinion. After two doses of radiation therapy, the patient's general condition rapidly deteriorated and she was hospitalized for systemic ICT. Despite the treatment, her condition continued to deteriorate, and she died 3 weeks after the presentation. Conclusion: The presented case demonstrates some hitherto unaddressed challenges in evaluation and treatment of mSCC caused by aggressive non-Hodgkin lymphoma (LSSC). The case scrutinizes the role of MRI in uncommon clinical situations. The case has also exposed some ethical issues associated with the proper management of LSCC. Established Facts: Metastatic spinal cord compression (mSCC) can complicate any type of malignancy, most commonly the breast, prostate and lung cancers. Non-Hodgkin lymphoma (NHL), however, demonstrates the highest cancer-specific SCC incidence with the majority being diffuse large B cell lymphomas. Lymphomatous SCC (LSCC) must be distinguished from the primary or secondary CNS lymphomas. The management of LSCC most commonly follows the same strategy as other malignancies and involves decompression surgery, local radiation treatment or both. Chemotherapy as a treatment of LSCC has been introduced as early as the 1970s, but its role and necessity in LSCC management have long remained controversial. The indications for, and the role of, diagnostic MRI in evaluation of LSCC, although well established, could be intricate and difficult to ascertain. [ABSTRACT FROM AUTHOR]

Background: This study compared the survival of persons with secondary acute myeloid leukemia (sAML) to those with de novo AML (dnAML) by age at AML diagnosis, chemotherapy receipt, and cancer type preceding sAML diagnosis. Methods: Data from Surveillance, Epidemiology, and End Results 17 Registries were used, which included 47,704 individuals diagnosed with AML between 2001 and 2018. Multivariable Cox proportional hazards regression was used to compare AML‐specific survival between sAML and dnAML. Trends in 5‐year age‐standardized relative survival were examined via the Joinpoint survival model. Results: Overall, individuals with sAML had an 8% higher risk of dying from AML (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.05–1.11) compared to those with dnAML. Disparities widened with younger age at diagnosis, particularly in those who received chemotherapy for AML (HR, 1.14; 95% CI, 1.10–1.19). In persons aged 20–64 years and who received chemotherapy, HRs were greatest for those with antecedent myelodysplastic syndrome (HR, 2.04; 95% CI, 1.83–2.28), ovarian cancer (HR, 1.91; 95% CI, 1.19–3.08), head and neck cancer (HR, 1.55; 95% CI, 1.02–2.36), leukemia (HR, 1.45; 95% CI, 1.12–1.89), and non‐Hodgkin lymphoma (HR, 1.42; 95% CI, 1.20–1.69). Among those aged ≥65 years and who received chemotherapy, HRs were highest for those with antecedent cervical cancer (HR, 2.42; 95% CI, 1.15–5.10) and myelodysplastic syndrome (HR, 1.28; 95% CI, 1.19–1.38). The 5‐year relative survival improved 0.3% per year for sAML slower than 0.86% per year for dnAML. Consequently, the survival gap widened from 7.2% (95% CI, 5.4%–9.0%) during the period 2001–2003 to 14.3% (95% CI, 12.8%–15.8%) during the period 2012–2014. Conclusions: Significant survival disparities exist between sAML and dnAML on the basis of age at diagnosis, chemotherapy receipt, and antecedent cancer, which highlights opportunities to improve outcomes among those diagnosed with sAML. In this cohort study of 47,704 persons with acute myeloid leukemia (AML), those with secondary AML had worse survival. The survival difference varied by age at diagnosis, antecedent cancer types, and chemotherapy receipt for AML. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: Myeloid and lymphoid malignant cells can become the dominant population in the bone marrow and thus inhibit healthy hematopoiesis. Patients suffer enormously as a result. In addition to the directly mediated inhibition of healthy hematopoietic stem and progenitor cells, indirect mechanisms via so-called mesenchymal stromal cells can also play a role. We are focusing our research on the latter and would like to identify functional and molecular overlapping mechanisms within the various myeloid and lymphoid neoplasms. In the future, it may be possible to block these mechanisms and thus prevent disease progression or improve healthy hematopoiesis. Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) have not been unraveled so far. Given the pivotal role of mesenchymal stromal cells (MSCs) in the regulation of hematopoiesis in the BM niche it is assumed that MSCs also play a relevant role in the pathogenesis of hematological neoplasms. We aimed to identify overlapping mechanisms in MSCs derived from myeloid and lymphoid neoplasms contributing to disease progression and suppression of HSPCs to develop interventions that target these mechanisms. MSCs derived from healthy donors (n = 44) and patients diagnosed with myeloproliferative neoplasia (n = 11), myelodysplastic syndromes (n = 16), or acute myeloid leukemia (n = 25) and B-Non-Hodgkin lymphoma (n = 9) with BM infiltration and acute lymphoblastic leukemia (n = 9) were analyzed for their functionality and by RNA sequencing. A reduced growth and differentiation capacity of MSCs was found in all entities. RNA sequencing distinguished both groups but clearly showed overlapping differentially expressed genes, including major players in the BMP/TGF and WNT-signaling pathway which are crucial for growth, osteogenesis, and hematopoiesis. Functional alterations in healthy MSCs were inducible by exposure to supernatants from malignant cells, implicating the involvement of these factors in disease progression. Overall, we were able to identify overlapping factors that pose potential future therapeutic targets. [ABSTRACT FROM AUTHOR]

Lenalidomide and rituximab (R2) is an effective frontline treatment for patients with indolent B-cell non-Hodgkin lymphoma (iNHL). We investigated the safety and efficacy of addition of the proteasome inhibitor ixazomib to R2 for treatment of iNHL through a phase I/II clinical trial for high-risk patients. Twenty patients were enrolled, 18 were treated. The target dose of ixazomib 4 mg weekly was achieved during dose escalation. The most common treatment-related adverse events (AEs) were low grade gastrointestinal, rash, neuropathy, and myalgia/arthralgia. There were 33% grade 2 and 17% grade 3 infections. With median follow-up of 5.2 years, four patients discontinued treatment due to lymphoma progression. Best overall response rate (ORR) was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. Kaplan-Meier estimates of progression free and overall survival (OS) were 73% and 87% at 36 months, respectively. R2 can safely be combined with ixazomib for treatment-naïve iNHL patients. [ABSTRACT FROM AUTHOR]

This article explores the use of stereotactic radiotherapy (SRT) as a potential treatment option for secondary central nervous system (CNS) lymphoma before chimeric antigen receptor modified T-cell (CAR-T) therapy. The authors present a case series of three patients who underwent SRT followed by CAR-T, resulting in successful outcomes and remission of CNS lymphoma without significant cognitive impairments. The article suggests that SRT could be a viable and effective bridging therapy for patients with CNS lymphoma before CAR-T, but further research is needed to determine the optimal dosage and timing of SRT in combination with systemic therapy. [Extracted from the article]

Marginal zone lymphomas (MZLs) are a rare, indolent group of non‐Hodgkin lymphomas with different diagnostic, genetic and clinical features and therapeutic implications. The most common is extranodal MZL of mucosa‐associated lymphoid tissue, followed by splenic MZL and nodal MZL. Patients with MZL generally have good outcomes with long survival rates but frequently have a relapsing/remitting course requiring several lines of therapy. The heterogeneous presentation and relapsing course present the clinician with several diagnostic and therapeutic challenges. This position statement presents evidence‐based recommendations in the setting of Australia and New Zealand. [ABSTRACT FROM AUTHOR]

BACKGROUND: Accumulating evidence suggests that domestic water hardness is linked to health outcomes, but its association to all-cause and causespecific cancers warrants investigation. OBJECTIVE: The aim of this study was to investigate the association of domestic hard water with all-cause and cause-specific cancers METHODS: In the prospective cohort study, a total of 447,996 participants from UK Biobank who were free of cancer at baseline were included and followed up for 16 y. All-cause and 22 common cause-specific cancer diagnoses were ascertained using hospital inpatient records and self-reported data until 30 November 2022. Domestic water hardness, measured by CaCO3 concentrations, was obtained from the local water supply companies across England, Scotland, and Wales in 2005. Data were analyzed using Cox proportional hazard models, with adjustments for known measured confounders, including demographic, socioeconomic, clinical, biochemical, lifestyle, and environmental factors RESULTS: Over a median follow-up of 13.6 y (range: 12.7–14.4 y), 58,028 all-cause cancer events were documented. A U-shaped relationship between domestic water hardness and all-cause cancers was observed (푝 for nonlinearity <0.001). In comparison with individuals exposed to soft water (0–60 mg/L), the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause cancer were 1.00 (95% CI: 0.98, 1.02) for those exposed to moderate hard water (>60–120 mg/L), 0.88 (95% CI: 0.84, 0.91) for those exposed to hard water (>120–180 mg/L) and 1.06 (95% CI: 1.04, 1.08) for those exposed to very hard water (>180 mg/L). Additionally, domestic water hardness was associated with 11 of 22 cause-specific cancers, including cancers of the esophagus, stomach, colorectal tract, lung, breast, prostate, and bladder, as well as non-Hodgkin lymphoma, multiple myeloma, malignant melanoma, and hematological malignancies. Moreover, we observed a positive linear relationship between water hardness and bladder cancer DISCUSSION: Our findings suggest that domestic water hardness was associated with all-cause and multiple cause-specific cancers. Findings from the UK Biobank support a potentially beneficial association between hard water and the incidence of all-cause cancer. However, very hard water may increase the risk of all-cause cancer. [ABSTRACT FROM AUTHOR]

Background: Currently, the Enterobacteriaceae species are responsible for a variety of serious infections and are already considered a global public health problem, especially in underdeveloped countries, where surveillance and monitoring programs are still scarce and limited. Analyses were performed on the complete genome of an extensively antibiotic-resistant strain of Enterobater hormaechei, which was isolated from a patient with non-Hodgkin's lymphoma, who had been admitted to a hospital in the city of Manaus, Brazil. Methods: Phenotypical identification and susceptibility tests were performed in automated equipment. Total DNA extraction was performed using the PureLink genomic DNA mini-Kit. The genomic DNA library was prepared with Illumina Microbial Amplicon Prep and sequenced in the MiSeq Illumina Platform. The assembly of the whole-genome and individual analyses of specific resistance genes extracted were carried out using online tools and the Geneious Prime software. Results: The analyses identified an extensively resistant ST90 clone of E. hormaechei carrying different genes, including blaCTX-M-15, blaGES-2, blaTEM-1A, blaACT-15, blaOXA-1 and blaNDM-1, [aac(3)-IIa, aac(6′)-Ian, ant(2″)-Ia], [aac(6′)-Ib-cr, (qnrB1)], dfrA25, sul1 and sul2, catB3, fosA, and qnrB, in addition to resistance to chlorhexidine, which is widely used in patient antisepsis. Conclusions: These findings highlight the need for actions to control and monitor these pathogens in the hospital environment. [ABSTRACT FROM AUTHOR]

Extranodal diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease process and an aggressive form of non-Hodgkin's lymphoma. We present a case of multiorgan involvement of DLBCL in a patient with documented risk factors, including [ 18 F] fluorodeoxyglucose positron emission tomography/magnetic resonance imaging findings highlighting striking perineural spread involving intracranial and extracranial segments of the bilateral trigeminal nerves. [ABSTRACT FROM AUTHOR]

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell–related biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: The intraventricular route of chemotherapy administration, via an Ommaya Reservoir (OmR) improves drug distribution in the central nervous system (CNS) compared to the more commonly used intrathecal administration. We retrospectively reviewed our experience with intraventricular chemotherapy, focused on methotrexate, in patients with Acute Lymphoblastic Leukemia (ALL) and Non-Hodgkin Lymphoma (NHL). Methods: Twenty-four patients (aged 7 days – 22.2 years) with 26 OmR placements were identified for a total of 25,009 OmR days between 1990 and 2019. Methotrexate cerebrospinal fluid (CSF) concentrations (n = 124) were analyzed from 59 courses of OmR therapy in 15 patients. Twenty-one courses involved methotrexate dosing on day 0 only, whereas 38 courses involved booster dosing on days 1, 2, or both. We simulated the time CSF methotrexate concentrations remained > 1 µM for 3 days given various dosing regimens. Results: CSF methotrexate exposure was higher in those who concurrently received systemic methotrexate than via OmR alone (p < 10− 7). Our simulations showed that current intraventricular methotrexate boosting strategy for patients ≥ 3 years of age maintained CSF methotrexate concentrations ≥ 1 µM for 72 h 40% of the time. Alternatively, other boosting strategies were predicted to achieve CSF methotrexate concentrations ≥ 1 µM for 72 h between 46 and 72% of the time. Conclusions: OmR were able to be safely placed and administer intraventricular methotrexate with and without boost doses in patients from 7 days to 22 years old. Boosting strategies are predicted to increase CSF methotrexate concentrations ≥ 1 µM for 72 h. [ABSTRACT FROM AUTHOR]

Mosunetuzumab (Mosun) is a CD20xCD3 T‐cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. The approved step‐up dose regimen of 1/2/60/30 mg IV is designed to mitigate cytokine release syndrome (CRS) and maximize efficacy in early cycles. A population pharmacokinetic (popPK) model was developed from 439 patients with relapsed/refractory B‐Cell Non‐Hodgkin lymphoma receiving Mosun IV monotherapy, including fixed dosing (0.05–2.8 mg IV every 3 weeks (q3w)) and Cycle 1 step‐up dosing groups (0.4/1/2.8–1/2/60/30 mg IV q3w). Prior to Mosun treatment, ~50% of patients had residual levels of anti‐CD20 drugs (e.g., rituximab or obinutuzumab) from prior treatment. CD20 receptor binding dynamics and rituximab/obinutuzumab PK were incorporated into the model to calculate the Mosun CD20 receptor occupancy percentage (RO%) over time. A two‐compartment model with time‐dependent clearance (CL) best described the data. The typical patient had an initial CL of 1.08 L/day, transitioning to a steady‐state CL of 0.584 L/day. Statistically relevant covariates on PK parameters included body weight, albumin, sex, tumor burden, and baseline anti‐CD20 drug concentration; no covariate was found to have a clinically relevant impact on exposure at the approved dose. Mosun CD20 RO% was highly variable, attributed to the large variability in residual baseline anti‐CD20 drug concentration (median = 10 μg/mL). The 60 mg loading doses increased Mosun CD20 RO% in Cycle 1, providing efficacious exposures in the presence of the competing anti‐CD20 drugs. PopPK model simulations, investigating Mosun dose delays, informed treatment resumption protocols to ensure CRS mitigation. [ABSTRACT FROM AUTHOR]

CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin's lymphoma (NHL). In patients receiving CAR-T-cell therapy, fluorodeoxyglucose Positron Emission Tomography/Computer Tomography ([18F]FDG PET/CT) plays a critical role in tracking treatment response and evaluating the immunotherapy's overall efficacy. The aim of this study is to provide a systematic review of the literature on the studies aiming to assess and predict toxicity by means of [18F]FDG PET/CT in patients with NHL receiving CAR-T-cell therapy. PubMed/MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were interrogated by two investigators to seek studies involving the use of [18F]FDG PET/CT in patients with lymphoma undergoing CAR-T-cell therapy. The comprehensive computer literature search allowed 11 studies to be included. The risk of bias for the studies included in the systematic review was scored as low by using version 2 of the "Quality Assessment of Diagnostic Accuracy Studies" tool (QUADAS-2). The current literature emphasizes the role of [18F]FDG PET/CT in assessing and predicting toxicity in patients with NHL receiving CAR-T-cell therapy, highlighting the evolving nature of research in CAR-T-cell therapy. Additional studies are warranted to increase the collected evidence in the literature. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are implicated in the regulation of immune responses closely associated with poor clinical outcomes in cancer. However, the MDSC subtypes in non-Hodgkin's lymphoma (NHL) have not been systematically investigated. So, we investigated the percentage of MDSC subsets in 78 newly diagnosed NHL patients by flow cytometry. The results showed that all MDSC subsets increased in NHL patients compared with healthy donors. Notably, MDSCs, monocytic MDSCs, and CD14 + CD66b + MDSCs significantly increased in NHL patients compared with those with lymphadenitis donors. polymorphonuclear MDSCs (PMN-MDSCs), early-stage MDSCs (e-MDSCs), and the International Prognostic Index were independent risk factors for poor clinical efficacy and were involved in constructing the nomogram for predicting clinical efficacy. Progression-free survival (PFS) was significantly shorter in patients with high level of MDSC subsets, and PMN-MDSCs emerged as an independent prognostic factor for PFS. PMN-MDSCs, e-MDSCs, and the International Prognostic Index were involved in constructing the nomogram for predicting PFS. Patients with a higher percentage of MDSCs, PMN-MDSCs, e-MDSCs, and CD14 + CD66b + MDSCs experienced a shorter overall survival compared with those with lower percentages. In addition, research on mechanisms found that T cell function was suppressed and mediated by the expansion of MDSCs via involving arginase-1 and interleukin-10 in vitro and in vivo. In conclusion, our study demonstrates that the increased circulating MDSC subsets predict poor clinical efficacy and prognosis in NHL, potentially involving T cell suppression through MDSC subset expansion. These findings indicate the potential of MDSC subsets as comprehensive diagnostic, prognostic biomarkers, and therapeutic targets for NHL. [ABSTRACT FROM AUTHOR]

Digital pathology involves the conversion of histology slides into digital format to generate high-resolution images. Tissue classification, particularly for identifying common types of non-Hodgkin lymphomas like mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia, is a crucial application of this technology. Due to the complexity of these lymphomas, pathologists often encounter challenges in their diagnosis. However, the limited availability of image data in the dataset poses a significant challenge. To solve this issue, we present a new technique for augmenting the dataset and enabling more efficient model training. In this article, we propose a technique capable of approaching lymphoma images. Our idea is to generate lymphoma images by adding a segmented image. The reference images are taken from the available dataset. We use two re neural networks. The first neural network is image-to-image translation, a technique used to transform the appearance or style of images, particularly adversarial neural networks, facilitates this process by using inputs from the source domain to produce images that closely match the target domain. The second neural network, we use an improved convolutional neural network (CNN) algorithm for classifying non-Hodgkin lymphomas. Trained on this augmented dataset, the proposed model achieves a classification accuracy of 99.91%. This precision is higher than that reported by Khelil et al. in their study. Moreover, we acknowledge the ethical implications of generating synthetic medical images and propose guidelines for ensuring the ethical conduct of our proposed technique. [ABSTRACT FROM AUTHOR]

Anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT) are rare cancers observed predominantly in children and young adults. ALCL accounts for 10–15% of all pediatric non-Hodgkin lymphomas and is commonly diagnosed at an advanced stage of disease. In children, 84–91% of cases of ALCL harbor an anaplastic lymphoma kinase (ALK) gene translocation. IMT is a rare mesenchymal neoplasm that also tends to occur in children and adolescents. Approximately 50–70% of IMT cases involve rearrangements in the ALK gene. A combination of chemotherapeutic drugs is typically used for children with ALK-positive ALCL, and the only known curative therapy for ALK-positive IMT is complete surgical resection. Crizotinib, a first-generation ALK inhibitor, was approved in the USA in 2021 for pediatric patients and young adults with relapsed or refractory ALK-positive ALCL; however, its safety and efficacy have not been established in older adults. In 2022, crizotinib was approved for adult and pediatric patients with unresectable, recurrent, or refractory ALK-positive IMT. This podcast provides an overview of ALK-positive ALCL and IMT. We discuss the current treatment landscape, the role of ALK tyrosine kinase inhibitors, and areas of future research. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is often considered a chronic disease with frequent relapses, shortening both response duration and survival after every relapse. Selecting the most appropriate therapy at the right time within the treatment timeline is key to optimize outcomes. The aim of this vodcast, featuring Dr. Kai Hübel, is to outline the severity of FL by referring to a patient case as well as highlight chimeric antigen receptor (CAR)-T cells as an effective therapy in relapsed/refractory (r/r) FL. The patient was in their early 50s, diagnosed with FL in the early 2010s and presented with a third relapse. The patient complained of night sweats and fatigue but was still capable of self-care (Eastern Cooperative Oncology Group Performance Status Scale 2). The patient received eight cycles of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP), followed by irradiation and rituximab maintenance (first-line) and then received rituximab 4 × weekly, followed by rituximab maintenance (second-line). The patient relapsed during rituximab maintenance; the patient was rituximab refractory. The patient received six cycles of bendamustine/obinutuzumab followed by obinutuzumab maintenance. The patient relapsed during obinutuzumab maintenance, achieved a partial remission after irradiation and was switched to R/lenalidomide. Due to several high-risk features, CAR-T cell therapy was initiated. Dr. Hubel underlines how earlier treatment with CAR-T cell therapy would have been beneficial for this patient. Results of the ELARA trial as well as comparative studies have shown tisagenlecleucel to be more effective than standard of care in extensively pretreated r/r FL, including high-risk patients. In conclusion, CAR-T cell therapy is a promising therapy option for patients with multiply r/r FL. A vodcast feature is available for this article. [ABSTRACT FROM AUTHOR]

Background: Multiple studies have suggested a possible connection between the gut microbiota and the development of lymphoma, though the exact nature of this relationship remains unclear. This study aimed to explore whether a causal association exists between gut microbiota and lymphoma. Methods: A bidirectional two-sample Mendelian randomization (MR) approach was conducted to investigate potential causal effects between gut microbiota and various lymphoma subtypes. The primary method employed for MR analysis was inverse variance weighted (IVW), supplemented by additional methods including MR-Egger, weighted median, and weighted mode approaches. The Cochrane Q test, MR-PRESSO global test and MR-Egger intercept test were performed to assess pleiotropy and heterogeneity. Furthermore, a reverse MR analysis was performed to explore potential reverse causal effect. Results: The primary MR analysis identified 36 causal relationships between genetic liabilities in gut microbiota and different lymphoma subtypes. Neither the MR-PRESSO test nor the MR-Egger regression detected any pleiotropy, and Cochran's Q test indicated no significant heterogeneity. Conclusions: Our MR analysis revealed substantial causal associations between gut microbiota and lymphoma, offering new insights into lymphoma prevention and management microbiota. [ABSTRACT FROM AUTHOR]

Background. Lymphomas are malignant lymphocyte neoplasms that globally account for 10% of cancers in individuals aged <20 years. Malignant lymphomas are divided into Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). Despite the availability of many therapeutic modalities for lymphoma, such as Brentuximab vedotin, Nivolumab, and Pembrolizumab, it is still necessary to identify appropriate strategies with minimal side effects. Immunotherapy is a promising approach, exemplified by targeting JAK/STAT3 signaling, which can inhibit tumor growth and enhance antitumor immune responses. Hence, STAT3 (signal transducer and activator of transcription 3) is a promising therapeutic target. PD-L1 (programmed death-ligand 1), an immune checkpoint molecule, is used as a frontline treatment for various cancers. This study aims to determine STAT3 expression and its correlation with PD-L1 expression in NHL and HL to serve as a basis for further research on anti-STAT3 and its combination with other therapy targets. Methods. Samples were obtained from paraffin blocks of patients with confirmed diagnoses of NHL and HL, and then immunohistochemical staining was carried out with PD-L1 and STAT3 antibodies. The collected data were then analyzed using SPSS. Results. Among the 10 HL patients, no patients (0%) expressed STAT3, while nine patients (90%) expressed PD-L1. Among the 10 NHL patients, 1 patient (10%) expressed STAT3, while six patients (60%) expressed PD-L1. There were no significant differences in STAT3 expression and PD-L1 expression between HL patients and NHL patients. There was no correlation between STAT3 and PD-L1 expression in HL and NHL because almost all STAT3 expressions were negative. Conclusion. Although this study revealed no differences between STAT3 and PD-L1 expression in HL and NHL and no significant correlation between STAT3 and PD-L1 expression in HL and NHL, this may serve as the basis for understanding the role of STAT3 and PD-L1 in the regulation of HL and NHL, which may be useful for further research targeting STAT3 and PD-L1 immunotherapy in HL and NHL. [ABSTRACT FROM AUTHOR]