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Summary: Background: There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. Aims: The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. Methods: We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population‐based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random‐effects meta‐analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). Results: We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21–1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06–1.53]) and non‐Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20–1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27–1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09–1.35]) (p for interaction = 0.026). Meta‐regression demonstrated that mean age of patients, study year, mean study follow‐up duration, and percentages of immunomodulators and biologics use did not influence study outcome. Conclusions: The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non‐Hodgkin's lymphoma. [ABSTRACT FROM AUTHOR]

Diffuse large B‐cell lymphoma (DLBCL) is the most common lymphoma entity, and its incidence increases with age. There is a paucity of data regarding use of biweekly R‐CHOP (R‐CHOP‐14) in patients ≥80 years of age. We performed a retrospective cohort study of patients with DLBCL aged ≥80 years treated with R‐CHOP‐14 and R‐miniCHOP in two academic tertiary centers in Germany between 01/01/2005 and 12/30/2019. Overall, 79 patients were included. Median age was 84 years (range 80–91). Despite higher CR rates with R‐CHOP‐14 (71.4% vs. 52.4%), no statistically significant difference could be found between patients treated with R‐CHOP‐14 and R‐miniCHOP regarding overall survival (OS) (p =.88, HR 0.94, 95% CI = 0.47–1.90) and progression‐free survival (PFS) (p =.26, HR 0.66, 95% CI = 0.32–1.36). At a median follow‐up of 40 months, the 2‐year OS rates were 56% with R‐CHOP‐14 and 53% with R‐miniCHOP. Two‐year PFS rates were 46% for R‐CHOP‐14 and 50% for R‐mini‐CHOP. Relative dose intensity of chemotherapy did not correlate with OS (p =.72). With the caveat of a retrospective cohort study, we conclude that lacking a difference in OS, R‐miniCHOP should be preferred for most patients with untreated DLBCL aged ≥80 years. [ABSTRACT FROM AUTHOR]

Summary Immune effector cell‐associated hematotoxicity (ICAHT) is a common toxicity associated with an important morbidity after chimeric antigen receptor (CAR)‐T‐cell therapy. Multiple factors seem to be involved in the development of severe ICAHT, making its management difficult. Here, we report three cases of severe ICAHT after axicabtagene‐ciloleucel (axi‐cel) for diffuse large B‐cell lymphoma showing an expansion of large granular lymphocyte in the bone marrow with a CD3/CD57‐positive non‐CAR‐T immunophenotype. We show that it is possible to treat them with low‐dose steroids, obtaining a striking resolution of cytopenias with no deleterious impact on the underlying malignancy. [ABSTRACT FROM AUTHOR]

The mature splenic B‐cell lymphomas are an enigmatic group of lymphoid neoplasms that have long caused significant difficulty for the practicing pathologist due to overlapping diagnostic features among entities and the decreasing availability of splenic tissue for assessment. While some entities have highly characteristic and specific clinicopathological features (e.g. hairy cell leukaemia), others are substantially more difficult to recognise (e.g. splenic diffuse red pulp lymphoma). At the same time, classification systems have been evolving, resulting in multiple changes to the boundaries among these entities and even the existence of some entities in their own right. Moreover, unbiased multi‐omic interrogation (whole genome/transcriptome sequencing, methylome) of the splenic B‐cell lymphomas over the past decade has given us significant insights into the underling biology of these neoplasms. We present a clinicopathological perspective on the historical, current and future state of the diagnosis and classification of splenic B‐cell lymphomas integrating multi‐omic data and highlighting areas of focus for the field in order to continue to strive to improve patient outcomes through accurate diagnosis. [ABSTRACT FROM AUTHOR]

Summary Grade 3B follicular lymphoma (G3BFL) is a rare lymphoma thought to sit on a continuum between low‐grade FL and diffuse large B‐cell lymphoma (DLBCL). The prognostic impact of quantitative positron emission tomography (PET) metrics such as total metabolic tumour volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUVmax) have been extensively analysed in FL and DLBCL, but G3BFL data are lacking. Here, we describe PET outcomes and radiomic characteristics in 46 G3BFL cases uniformly treated with R‐CHOP (like) chemotherapy. Central semi‐automated PET TMTV, TLG, and SUVmax analyses, using MIM software, were correlated with clinical outcomes and compared with published results in low‐grade FL and DLBCL. In G3BFL, the end‐of‐treatment complete metabolic response was associated with improved progression‐free survival (PFS; p = 0.002) and overall survival (OS; p = 0.04). G3BFL median TLG (1455) and SUVmax (16.50) sit between published values for low‐grade FL (TLG: 1112, SUVmax: 11.3) and DLBCL (TLG: 3004, SUVmax: 24.35). No association between TMTV (>350 cm3) and survival was seen (PFS: p = 0.24; OS: p = 0.40). High SUVmax (>19.2) and TLG (>2760) both conferred inferior PFS but not OS (PFS: SUVmax p = 0.004; TLG p = 0.05). These data support the routine incorporation of PET radiomics at baseline and treatment response for G3BFL. [ABSTRACT FROM AUTHOR]

ABSTRACT Primary testicular lymphoma (PTL) is a rare occurrence of diffuse large B‐cell lymphoma (DLBCL) that accounts for 1%–2% of all cases. Nodal DLBCL with testis involvement (DLBCL‐T) and PTL are associated with poor prognosis, with high incidence of central nervous system relapse. Fifteen patients (median age 60 years) with PTL (n = 5) or DLBCL‐T (n = 10) received high‐dose methotrexate + R‐CHOP. Overall, complete response (CR) rate was 73% and overall response rate 86%. With a 3.9‐year median follow‐up, 100% of patients with PTL had CR and none relapsed. On the contrary, 55% of DLBCL‐T patients achieved CR among which only one was still in remission at the end of follow‐up. Molecular parallels between PTL and Primary CNS Lymphoma (PCNSL) suggest shared origins, urging further research for tailored treatments and enhanced understanding of these lymphomas' biology. [ABSTRACT FROM AUTHOR]

Summary: Secondary primary malignancies (SPM) have been reported after anti‐BCMA or anti‐CD19 chimeric antigen receptor (CAR)‐T‐cell therapies. While the cytotoxic effect of antecedent therapies, including chemotherapy and radiotherapy, has been well established, few data are available on risk related to CAR‐T immunotherapies. The study aimed to analyse the incidence of SPM in 651 patients enrolled in the Italian prospective observational CART‐SIE study. SPMs were documented in 4.3% (28/651), and the most frequent SPMs were haematological malignancies. In conclusion, the frequency of SPMs in our cohort of heavily pretreated patients receiving CAR‐T was relatively low and consistent with previous studies. [ABSTRACT FROM AUTHOR]

Summary: The documented treatment‐induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995–2015 and aged 15–40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I–II and 33.5% had stage III–IV disease. With a median follow‐up of 14.76 years, 139 deaths occurred, yielding a 5‐year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL‐related death showed an initial sharp rise, with a plateau at 5.3% 10‐year post‐diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20‐year mark respectively. HL cases had a 7.5‐fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause‐specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches. [ABSTRACT FROM AUTHOR]

Summary The clinical and prognostic implications of nodal involvement (NI) in Waldenström macroglobulinaemia (WM) are largely unknown. In this study, we explored the impact of NI on clinical presentation and outcome in a population‐based cohort of 469 patients with WM, consecutively diagnosed between 2000 and 2022. NI was detected in 34% of patients and was associated with symptomatic disease, adverse prognostic factors, an increased risk of transformation, and lymphoma‐related death. Our findings indicate that NI is of prognostic significance in WM, suggesting a need for enhanced surveillance in these patients. [ABSTRACT FROM AUTHOR]

Summary Acalabrutinib is a selective, second‐generation Bruton tyrosine kinase inhibitor. In this open‐label, parallel‐group study, patients with relapsed/refractory (R/R) follicular lymphoma (FL) were randomised to either acalabrutinib monotherapy or acalabrutinib plus rituximab. An additional cohort of patients with treatment‐naive (TN) FL received only the acalabrutinib‐rituximab combination. Acalabrutinib‐rituximab was well tolerated and active in R/R and TN FL; in the TN cohort the overall response rate was 92.3% with most remissions lasting over 4 years. Acalabrutinib monotherapy was also well tolerated and active in R/R FL. These results support further study of acalabrutinib alone and in combination with rituximab in FL. [ABSTRACT FROM AUTHOR]

Primary cutaneous gamma/delta (γδ) T‐cell lymphoma (PCGDTCL) is a rare, aggressive malignant neoplasm of γδ T lymphocytes arising within the skin and subcutis. We present a challenging case of PCGDTCL diagnosed in a 35‐year‐old male soldier who presented with constitutional symptoms, pancytopenia, hemophagocytic lymphohistiocytosis (HLH), disseminated lymphadenopathy, and cutaneous lesions on his extremities and back following a deployment to Iraq and Syria. Histopathologic evaluation of an excisional biopsy showed that PCGDTCL can be focal, localized to the subcutaneous adipose tissue, and obscured by predominant HLH in the surrounding tissues. Pathologists should recognize that the diagnosis of PCGDTCL may be confounded by florid HLH and require multiple biopsies and a comprehensive immunohistochemical panel. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusion Recent front‐line clinical trials used the International Prognostic Index (IPI) to identify trial‐eligible patients with newly diagnosed diffuse large B‐cell lymphoma (DLBCL). However, many IPI‐like variants with improved accuracy have been developed over the years for rituximab‐treated patients.We assessed the impact of International Prognostic Indices on patient enrolment in clinical trials, aiming to exclude low‐risk IPI patients based on POLARIX/EPCORE DLBCL‐2 trial criteria.We identified 2877 patients in the Danish Lymphoma Registry who would have been eligible for the POLARIX trial if patients with IPI 0–1 scores were included. IPI and NCCN‐IPI assigned 33.3% and 11.9% of patients to the low‐risk group, respectively. Shorter 5‐year overall survival (91.4% vs. 97.5%), higher relapse rate (9.9% vs. 4.4%), and more deaths (16.1% vs. 4.4%) occurred in the low‐risk IPI group compared with low‐risk NCCN‐IPI group. Analyzed models failed to identify true high‐risk patients with poor prognosis. Similar results were found in the confirmatory cohort developed based on EPCORE DLBCL‐2 trial eligibility criteria.True low‐risk patients are more optimal identified by NCCN‐IPI and should be excluded from front‐line clinical trials due to their excellent prognosis. However, additional high‐risk factors besides clinical prognostic models need to be considered when selecting trial‐eligible patients. [ABSTRACT FROM AUTHOR]

Summary Validation of biobanks and large cancer cohorts is essential in ensuring high‐quality research results. We examined the coverage, generalisability and validity of the lymphoma collection of the Uppsala‐Umeå Comprehensive Cancer Consortium (U‐CAN) biobank in Sweden, one of the largest cancer biobanks in Europe. Up until 2022, 889 lymphoma patients in U‐CAN Uppsala had available samples, and 329 in U‐CAN Umeå. Patients diagnosed in the U‐CAN Uppsala area 2011–2021 (n = 843) were linked to the nationwide Swedish Lymphoma Register, and a subset diagnosed before 2019 (n = 727) to population‐based registers. The coverage was 39% of all lymphoma patients between 2011 and 2019 diagnosed in the U‐CAN Uppsala area, with a pandemic decline to 10% during 2020–2021. The patients included had superior overall survival (hazard ratio = 0.70 [95% confidence interval, CI: 0.60–0.82]) than all lymphoma patients in Sweden. They had better performance status, were younger (odds ratio [OR] = 0.21 [95% CI: 0.13–0.34]) and had less comorbidities (OR = 0.66 [95% CI: 0.56–0.78]). However, cause‐specific survival and stage distribution were similar. The questionnaire data captured less comorbidities compared to the national registers. Evaluations of biobanks are important, as even population‐based biobanks such as U‐CAN select younger patients with higher socioeconomical status and better performance status. However, the similar cause‐specific survival as in the registries suggests U‐CANs usefulness for prognostic biomarker studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Unilateral tonsillar enlargement (UTE) generally prompts suspicion of malignancy and tonsillectomy is often performed for histological diagnosis. This may be unnecessary in asymptomatic patients. We performed a retrospective study of all patients who had asymptomatic UTE and underwent tonsillectomy over a 5‐year period. We found no malignancies in our cohort of 78 patients. 22 out of 74 (29.7%) patients had a difference of 50% or more in the size of their tonsils. Around 1 in 4 patients had an inaccurate clinical diagnosis of UTE compared to the final size of their tonsil specimens. In a comprehensive literature review, only 2 out of 1152 patients (0.17%) were found to have lymphoma with UTE as the only presenting symptom and no other suspicious features. There can be huge variability between the size of normal tonsils. UTE alone without any other concerning features should prompt clinicians to consider other management options such as a period of observation rather than diagnostic tonsillectomy. [ABSTRACT FROM AUTHOR]

Summary: Twenty years after the conceptual revolution that occurred in the millennium turnaround upon the introduction of PET/CT in lymphoma staging, restaging, and prognostication, a number of new parameters for PET reading have been proposed: (1) the shift from a qualitative to a semi‐quantitative reading for PET reporting, (2) an international consensus on these novel interpretation keys, (3) a standardized and agreed procedure to measure the total metabolic tumour volume (TMTV), and (4) the proposition of new indexes to portray the tumour spread: (D‐Max and Total Lesion Surface –TLS). These proved to be very powerful prognosticators, able to revolutionize the traditional Ann Arbor four‐stage lymphoma staging. During the 17° Lugano meeting on lymphoma, one main question was asked to experts attending a closed workshop dedicated to new metrics for lymphoma diagnosis, staging, restaging, and prognostication: "Should the traditional 4‐stage anatomic staging system be simplified to a more clinically relevant 2‐stage system (e.g., limited vs. extensive disease)?" Early‐stage HL is an example of how these new metrics could fit with this proposal. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We report a rare case of thyroid diffuse large B‐cell lymphoma with a BRAFV600E mutation, which mimics poorly differentiated thyroid cancer in fine needle aspiration cytology. [ABSTRACT FROM AUTHOR]

Multiagent chemotherapy is considered the most effective treatment for canine high‐grade lymphoma; however, due to cost and time requirements, single‐agent protocols have also been described. The aim of our study was to evaluate the outcome and prognostic factors of dogs affected by multicentric lymphoma treated with lomustine and prednisolone as first‐line treatment. Cases of medium‐large‐cell multicentric lymphoma treated with lomustine and prednisolone were included in the study. Response to therapy, time to progression (TTP), median disease‐free interval (MDFI) and median survival time (MST) were retrospectively described. Thirty cases were included. Eleven (36.67%) were T cell, 11 (36.67%) were B cell and 8 (26.66%) had unknown immunophenotype. The overall response rate (RR) was 87%, with 15 patients achieving CR (50%) and 11 patients PR (37%). The median TTP, MDFI and MST were 42, 63 and 90 days, respectively. The only factor significantly associated with MDFI and MST was the stage. Dogs with multicentric lymphoma treated with lomustine and prednisolone have lower RR, TTP, MDFI and MST compared with dogs receiving multiagent protocols. Based on the short‐lasting response, this study confirms that this protocol might have minimal utility beyond palliation. [ABSTRACT FROM AUTHOR]

Biomarkers for immune checkpoint inhibitors (ICIs) response and resistance include PD‐L1 expression and other environmental factors, among which the gut microbiome (GM) is gaining increasing interest especially in lymphomas. To explore the potential role of GM in this clinical issue, feces of 30 relapsed/refractory lymphoma (Hodgkin and primary mediastinal B‐cell lymphoma) patients undergoing ICIs were collected from start to end of treatment (EoT). GM was profiled through Illumina, that is, 16S rRNA sequencing, and subsequently processed through a bioinformatics pipeline. The overall response rate to ICIs was 30.5%, with no association between patients clinical characteristics and response/survival outcomes. Regarding GM, responder patients showed a peculiar significant enrichment of Lachnospira, while non‐responder ones showed higher presence of Enterobacteriaceae (at baseline and maintained till EoT). Recognizing patient‐related factors that may influence response to ICIs is becoming critical to optimize the treatment pathway of heavily pretreated, young patients with a potentially long‐life expectancy. These preliminary results indicate potential early GM signatures of ICIs response in lymphoma, which could pave the way for future research to improve patients prognosis with new adjuvant strategies. [ABSTRACT FROM AUTHOR]

Summary This Good Practice Paper provides recommendations for the baseline investigation, risk stratification and use of prophylactic interventions for patients with large B‐cell lymphoma at risk of central nervous system relapse. Recent evidence which has questioned the role of high‐dose methotrexate in this clinical scenario is discussed in detail. [ABSTRACT FROM AUTHOR]

Summary: Primary gastric diffuse large B‐cell lymphoma (PG‐DLBCL) accounts for the majority of extra‐nodal DLBCL. Even so, literature is lacking on early, localised presentations. We studied a cohort of patients with stage I disease, diagnosed between 2006 and 2018, from six centres between Australia, Canada and Denmark. Our goal was to characterise outcomes, review treatment and investigate the role of interim positron emission tomography (iPET). Thirty‐seven eligible patients were identified. The median duration of follow‐up was 42.2 months. All received chemoimmunotherapy with 91.9% (n = 34) given rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R‐CHOP). 35.1% (n = 13) underwent consolidative radiotherapy. Eighteen patients were H. pylori positive and 11 had the documentation of H. pylori eradication therapy. The 4‐year progression‐free survival and overall survival of R‐CHOP was 88% (95% CI: 71–95) and 91% (95% CI: 75–97) respectively. All patients who achieved a partial metabolic response or complete metabolic response on iPET went on to achieve complete response at the end of treatment. R‐CHOP‐based therapy with iPET assessment appears to offer favourable outcomes, with radiotherapy and H. pylori eradication therapy implemented on a case‐by‐case basis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Primary gastric diffuse large B‐cell lymphoma (DLBCL), a rare malignancy linked to Helicobacter pylori (HP) infection, in this case regressed to low‐grade lymphoma and then achieved complete remission after HP eradication (HPE), highlighting this unique interim change and the potential of HPE as an effective treatment for early‐stage cases. Primary gastric diffuse large B‐cell lymphoma (DLBCL) is a rare malignancy. Like gastric mucosa‐associated lymphoid tissue (MALT) lymphoma, HP infection is implicated in lymphomagenesis and has thus emerged as a therapeutic target. Studies have demonstrated the sustained efficacy of HP eradication alone for limited‐stage primary gastric DLBCL. This report presents the case of a 53‐year‐old woman with stage IE gastric DLBCL who received triple therapy for HP eradication and experienced an interim histological transformation to MALT lymphoma, ultimately achieving complete pathologic remission. HP eradication therapy may represent a viable treatment option for patients with early‐stage primary gastric DLBCL. [ABSTRACT FROM AUTHOR]

The classification of primary cutaneous lymphomas and lymphoproliferative disorders (LPD) is continuously evolving by integrating novel clinical, pathological and molecular data. Recently two new classifications for haematological malignancies including entities of cutaneous lymphomas were proposed: the 5th edition of the WHO classification of haematolymphoid tumours and the International Consensus Classification (ICC) of mature lymphoid neoplasms. This article provides an overview of the changes introduced in these two classifications compared to the previous WHO classification. The main changes shared by both classifications include the downgrading of CD8+ acral T‐cell lymphoma to CD8+ acral T‐cell LPD, and the recognition of entities that were previously categorized as provisional and have now been designated as definite types including primary cutaneous small or medium CD4+ T‐cell LPD, primary cutaneous gamma/delta T‐cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T‐cell lymphoma, Epstein–Barr virus‐positive mucocutaneous ulcer. Both classifications consider primary cutaneous marginal zone B‐cell clonal neoplasm as an indolent disease but use a different terminology: primary cutaneous marginal zone lymphoma (WHO) and primary cutaneous marginal zone LPD (ICC). The 5th WHO classification further introduces and provides essential and desirable diagnostic criteria for each disease type and includes chapters on reactive B‐ or T‐cell rich lymphoid proliferations formerly referred as cutaneous pseudolymphomas, as well as histiocyte and CD8 T‐cell rich LPD in patients with inborn error of immunity. As already emphasized in previous lymphoma classifications, the importance of integrating clinical, histological, phenotypic and molecular features remains the crucial conceptual base for defining cutaneous (and extracutaneous) lymphomas. [ABSTRACT FROM AUTHOR]

Invariant natural killer T (iNKT) cells are a conserved population of innate T lymphocytes that are uniquely suitable as off‐the‐shelf cellular immunotherapies due to their lack of alloreactivity. Two major subpopulations of human iNKT cells have been delineated, a CD4− subset that has a TH1/cytolytic profile, and a CD4+ subset that appears polyfunctional and can produce both regulatory and immunostimulatory cytokines. Whether these two subsets differ in anti‐tumour effects is not known. Using live cell imaging, we found that CD4− iNKT cells limited growth of CD1d+ Epstein–Barr virus (EBV)‐infected B‐lymphoblastoid spheroids in vitro, whereas CD4+ iNKT cells showed little or no direct anti‐tumour activity. However, the effects of the two subsets were reversed when we tested them as adoptive immunotherapies in vivo using a xenograft model of EBV‐driven human B cell lymphoma. We found that EBV‐infected B cells down‐regulated CD1d in vivo, and administering CD4− iNKT cells had no discernable impact on tumour mass. In contrast, xenotransplanted mice bearing lymphomas showed rapid reduction in tumour mass after administering CD4+ iNKT cells. Immunotherapeutic CD4+ iNKT cells trafficked to both spleen and tumour and were associated with subsequently enhanced responses of xenotransplanted human T cells against EBV. CD4+ iNKT cells also had adjuvant‐like effects on monocyte‐derived DCs and promoted antigen‐dependent responses of human T cells in vitro. These results show that allogeneic CD4+ iNKT cellular immunotherapy leads to marked anti‐tumour activity through indirect pathways that do not require tumour cell CD1d expression and that are associated with enhanced activity of antigen‐specific T cells. [ABSTRACT FROM AUTHOR]

Primary effusion lymphoma (PEL) is a rare B‐cell non‐Hodgkin lymphoma associated with Kaposi Sarcoma‐associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein‐Barr virus (EBV) in 60−80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow‐Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations. [ABSTRACT FROM AUTHOR]

Summary Camidanlumab tesirine (ADCT‐301) is a CD25‐specific antibody‐drug conjugate (ADC) employing SG3199, a highly cytotoxic DNA minor groove cross‐linking pyrrolobenzodiazepine dimer. The ADC has shown early clinical antitumour activity in various cancers, including B‐ and T‐cell lymphomas. We assessed its preclinical activity as a single agent in 57 lymphoma cell lines and in combination with selected drugs in T‐cell lymphoma‐derived cell lines. Cells were exposed to increasing concentrations of the ADC or SG3199 for 96 h, followed by an MTT proliferation assay. CD25 expression was measured at cell surface and RNA levels. Experiments with PDX‐derived cell lines were used for validation studies. Camidanlumab tesirine presented more potent single agent in vitro cytotoxic activity in T‐ than B‐cell lymphomas. In vitro activity was correlated with CD25 cell surface and RNA expression. In vitro activity was correlated with CD25 cell surface and RNA expression. When camidanlumab tesirine‐containing combinations were evaluated in four T‐cell lymphoma models, the most active partners were everolimus, copanlisib, venetoclax, vorinostat, and pralatrexate, followed by bortezomib, romidepsin, bendamustine, and 5‐azacytidine. The strong camidanlumab tesirine single‐agent anti‐lymphoma activity and the in vitro synergisms with targeted agents identify potential combination partners for future clinical studies. [ABSTRACT FROM AUTHOR]

Posttransplantation primary cutaneous T‐cell lymphomas (PT‐CTCL) are a rare complication of sustained immunosuppression in the posttransplant setting. When present, PT‐CTCLs are typically EBV− and exhibit features of mycosis fungoides/Sézary syndrome or CD30+ lymphoproliferative disorders. We present a case of a 75‐year‐old individual who developed skin lesions 30 years after liver transplantation. Pathologic evaluation of the skin biopsy revealed involvement by a clonal, EBV+ T‐cell population of gamma/delta lineage with no evidence of systemic disease. Comprehensive genomic profiling was performed, confirming focal one‐copy loss of 6q23.3, altogether consistent with the extremely rare and unusual diagnosis of primary cutaneous EBV+ extranodal NK/T‐cell lymphoma of gamma/delta T‐cell lineage in the posttransplantation setting. [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: Peripheral T‐cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long‐term outcomes. The International T‐cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long‐term outcome analysis on patients from the ITCLP with available 10‐year follow‐up data (n = 735). The overall response rate to first‐line therapy was 68%, while 5‐ and 10‐year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5‐ to 10‐year period (67%). Low‐risk International Prognostic Index and Prognostic Index for T‐cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2–4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front‐line therapeutic approaches in PTCLs. [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]

Background: The aim of this study was to determine and describe the prognostic role of the morphological subtype determined according to the updated Kiel classification in dogs with high‐grade T‐cell lymphomas (HGTCLs) depending on the treatment applied. Objectives: The HGTCLs were classified into three subtypes according to the updated Kiel classification: pleomorphic mixed (PM), lymphoblastic lymphoma/acute lymphoblastic leukaemia and plasmacytoid (P). The treatment was divided into a palliative therapy (PlT) group and a chemotherapy (ChT) group. Methods: The study was conducted between 2009 and 2017, and it enrolled 58 dogs in which cytomorphological and immunocytochemistry diagnoses were HGTCL. Results: Overall survival (OS) was significantly longer in the ChT group (median OS—4 months, interquartile range [IQR] from 2 to 8 months) than in the PlT group (median OS—6 weeks, IQR from 1 week to 3 months). In the PlT group, PM subtype and glucocorticosteroids (GCSs) treatment proved significantly and independently linked to longer OS and approximately three‐fold lower risk of death during the study period (adjusted hazard ratio [HRadj] = 0.26, confidence interval [CI] 95%: 0.08–0.81; p = 0.020 and HRadj = 0.30, CI 95%: 0.11–0.77; p = 0.013, respectively), although due to small group size, precision of estimations was poor (wide CI 95%). In the ChT group, >7 days elapsing between diagnosis and the beginning of chemotherapy and GCS treatment prior to chemotherapy were significantly associated with lower chance of complete remission (CR; p = 0.034 for both); GCS treatment prior to chemotherapy was significantly associated with shorter OS (p = 0.016); chemotherapy based on the modified CHOP protocol was significantly associated with higher chance of CR (p = 0.034) and longer OS (p = 0.039); and CR was significantly linked to longer OS (p = 0.001). Clinical significance: The morphological subtype of HGTCL has some prognostic value in dogs treated palliatively (with PM subtype associated with longer OS than P subtype); however, this effect is no longer visible when a dog is treated with chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing autologous hematopoietic cell transplantation (HCT) have a >2‐fold risk of developing cardiovascular disease (CVD; heart failure, myocardial infarction, and stroke), compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in nononcology patients but is not as well studied in patients who underwent HCT and survivors of HCT.The objective of this study was to examine the association between CAC and CVD risk and outcomes after HCT in patients with lymphoma. Methods: This was a retrospective cohort study of 243 consecutive patients who underwent a first autologous HCT for lymphoma between 2009 and 2014. CAC (Agatston score) was determined from chest computed tomography obtained <60 days from HCT. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CIs), adjusted for covariates (age, conventional risk factors [e.g., hypertension and dyslipidemia], and cancer treatment). Results: The median age at HCT was 55.7 years (range, 18.5–75.1 years), 59% were male, and 60% were non‐Hispanic White. The prevalence of CAC was 37%. The 5‐year CVD incidence for the cohort was 12%, and there was an incremental increase in the incidence according to CAC score: 0 (6%), 1–100 (20%), and >100 (32%) (p =.001). CAC was significantly associated with CVD risk (HR, 3.0; 95% CI, 1.2–7.5) and worse 5‐year survival (77% vs. 50%; p <.001; HR, 2.0; 95% CI, 1.1–3.4), compared to those without CAC. Conclusions: CAC is independently associated with CVD and survival after HCT. This highlights the importance of integrating readily available imaging information in risk stratification and decision‐making in patients undergoing HCT, which sets the stage for strategies to optimize outcomes after HCT. Hematopoietic cell transplantation (HCT) survivors have an increased risk of cardiovascular disease (CVD) compared to the general population, and therefore thorough assessment of cardiovascular risk before HCT is essential. This study showed that the coronary artery calcium (CAC) score, obtained from routine pretransplant imaging, is significantly associated with CVD posttransplant and is a useful addition to traditional cardiovascular risk factors. Further prospective studies are needed to understand how CAC screening should be formally incorporated into pretransplant workup, cardiovascular risk assessment, and clinical decision‐making and its effect on posttransplant outcomes. [ABSTRACT FROM AUTHOR]

Summary: In this multicentre, real‐world study, we aimed to identify the clinical outcomes and safety of allogeneic haematopoietic stem cell transplantation (allo‐HSCT) in T‐lymphoblastic lymphoma (T‐LBL). A total of 130 Ann Arbor stage III or IV T‐LBL patients (>16 years) treated with allo‐HSCT across five transplant centres were enrolled. The 2‐year cumulative incidence of disease progression, the probabilities of progression‐free survival (PFS), overall survival (OS) and non‐relapse mortality (NRM) after allo‐HSCT were 21.0%, 69.8%, 79.5% and 9.2% respectively. Patients with central nervous system (CNS) involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, HR 3.78, p = 0.014). Patients receiving allo‐HSCT in non‐remission (NR) had a poorer PFS compared with those receiving allo‐HSCT in complete remission (CR) or partial remission (49.2% vs. 72.7%, HR 2.21, p = 0.041). Particularly for patients with bone marrow involvement and achieving CR before allo‐HSCT, measurable residual disease (MRD) positivity before allo‐HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8%, HR 1.94, p = 0.036). On multivariate analysis, CNS involvement at diagnosis and receiving allo‐HSCT in NR were associated with disease progression. Thus, our real‐world data suggested that allo‐HSCT appeared to be an effective therapy for adult T‐LBL patients with Ann Arbor stage III or IV disease. [ABSTRACT FROM AUTHOR]

Summary: Although progression‐free survival (PFS) is a commonly used surrogate end‐point for clinical trials of follicular lymphoma (FL), no analyses have evaluated the strength of surrogacy for PFS with overall survival (OS). A systematic review was performed and 20 studies (total participants, 10 724) met final inclusion criteria. PFS was weakly associated with OS (correlation coefficient; 0.383, p < 0.001). The coefficient of determination was 0.15 (95% CI: 0.002–0.35) suggesting 15% of OS variance could be explained by changes in PFS. This challenges the role for PFS as a surrogate end‐point for clinical trials and drug approvals. [ABSTRACT FROM AUTHOR]

Summary: Multiagent chemoimmunotherapy remains the standard of care treatment for Burkitt lymphoma leading to a cure in the majority of cases. However, frontline treatment regimens are associated with a significant risk of treatment related toxicity especially in elderly and immunocompromised patients. Additionally, prognosis remains dismal in refractory/relapsed Burkitt lymphoma. Thus, novel therapies are required to not only improve outcomes in relapsed/refractory Burkitt lymphoma but also minimize frontline treatment related toxicities. Recurrent genomic changes and signalling pathway alterations that have been implicated in the Burkitt lymphomagenesis include cell cycle dysregulation, cell proliferation, inhibition of apoptosis, epigenetic dysregulation and tonic B‐cell receptor‐phosphatidylinositol 3‐kinase (BCR‐PI3K) signalling. Here, we will discuss novel targeted therapy approaches using small molecule inhibitors that could pave the way to the future treatment landscape based on the understanding of recurrent genomic changes and signalling pathway alterations in the lymphomagenesis of adult Burkitt lymphoma. [ABSTRACT FROM AUTHOR]

Background: Glofitamab is a bispecific antibody with promise for treating relapsed/refractory B‐cell lymphoma according to a phase 1/2 clinical trial. This study examined its real‐world effectiveness. Methods: This was an investigator‐initiated, multicenter retrospective study including 34 patients who had relapsed/refractory B‐cell lymphomas after at least three prior lines of therapy and received glofitamab monotherapy in a compassionate use program in Taiwan between January 2021 and October 2022. Results: At a median follow‐up of 15.9 months, 56% of patients responded to glofitamab and 23% achieved complete remission. Response to the previous line of therapy significantly correlated with response to glofitamab (p =.020). Most responses were durable; only five out of the 19 responders had documented disease recurrence at the data cutoff date. The estimated progression‐free survival (PFS) was 3.2 months, and the estimated 1‐year PFS was 33% for the entire cohort. PFS was better for responders than nonresponders (median PFS, 16.9 vs. 1.8 months; 1‐year PFS, 60% vs. 0%). Forty‐three cytokine release syndrome (CRS) events were observed, three of which were grade 3; all were manageable without glofitamab discontinuation. No immune effector cell–associated neurotoxicity was reported. Among seven hepatitis B virus (HBV) carriers (six had antiviral prophylaxis) and 14 patients with remote HBV (four had antiviral prophylaxis), no HBV reactivation was observed. Conclusions: In this real‐world cohort, glofitamab exhibited effectiveness comparable to trial results without excessive CRS or new safety issues. With appropriate prophylaxis, glofitamab‐treated patients with chronic or remote HBV infection are unlikely to experience virus reactivation. [ABSTRACT FROM AUTHOR]

For CNS lymphomas (CNSL), there is a high need for minimally invasive and easily obtainable diagnostic markers. Intrathecal IgM synthesis can easily be determined in routine CSF diagnostics. The aim of this study was to systematically investigate the diagnostic potential of intrathecal IgM synthesis in primary and secondary CNSL (PCNSL and SCNSL). In this retrospective study, patients with a biopsy‐proven diagnosis of PCNSL or SCNSL were compared with patients with other neurological diseases in whom CNSL was initially the primary radiological differential diagnosis based on MRI. Sensitivity and specificity of intrathecal IgM synthesis were calculated using receiver operating characteristic curves. Seventy patients with CNSL were included (49 PCNSL and 21 SCNSL) and compared to 70 control patients. The sensitivity and specificity for the diagnosis of CNSL were 49% and 87%, respectively, for the entire patient population and 66% and 91% after selection for cases with tumor access to the CSF system and isolated intrathecal IgM synthesis. In cases with MRI‐based radiological suspicion of CNSL, intrathecal IgM synthesis has good specificity but limited sensitivity. Because of its low‐threshold availability, analysis of intrathecal IgM synthesis has the potential to lead to higher diagnostic accuracy, especially in resource‐limited settings, and deserves further study. [ABSTRACT FROM AUTHOR]

The current standard of care treatment for canine lymphoma is a multi‐agent, CHOP‐based chemotherapy protocol. Single agent doxorubicin (DOX) is less burdensome; however, multi‐agent chemotherapy protocols are often superior. The recently approved drug rabacfosadine (RAB, Tanovea) provides an attractive option for combination therapy with DOX, as both drugs demonstrate efficacy against lymphoma and possess different mechanisms of action. A previous study evaluating alternating RAB/DOX reported an overall response rate (ORR) of 84%, with a median progression‐free survival time (PFS) of 194 days. The aim of this prospective trial was to evaluate the same protocol in an additional population of dogs. Fifty‐nine dogs with treatment naïve lymphoma were enrolled. RAB (1.0 mg/kg IV) was alternated with DOX (30 mg/m2 IV) every 21 days for up to six total treatments (3 cycles). Response assessment and adverse event (AE) evaluation were performed every 21 days using VCOG criteria. The ORR was 93% (79% CR, 14% PR). The median time to maximal response was 21.5 days; median PFS was 199 days. T cell immunophenotype and lack of treatment response were predictive of inferior outcomes. AEs were mostly gastrointestinal. Six dogs developed presumed or confirmed pulmonary fibrosis; four were grade 5. One dog experienced grade 3 extravasation injury with RAB that resolved with supportive treatment. These data mirror those of the previously reported RAB/DOX study, and support the finding that alternating RAB/DOX is a reasonable treatment option for canine lymphoma. [ABSTRACT FROM AUTHOR]

Despite an initial strong response in most dogs with multicentric lymphoma treated with chemotherapy, relapse remains common. There is no clearly superior first rescue protocol described either for resistant or relapsed canine multicentric lymphoma. The objectives of this study were to assess clinical response and outcomes for canine multicentric lymphoma treated with first rescue protocols. The secondary objective was to assess prognostic variables for dogs undergoing these protocols. This was a bi‐institutional retrospective cohort study. Two hundred and sixty‐five dogs were treated with first rescue chemotherapy, including anthracycline‐based combination chemotherapy (CHOP‐like, n = 50), nitrosourea alkylating agent‐rich chemotherapy (n = 45), anthracycline‐based or related compound chemotherapy (n = 34), or nitrosourea single‐agent chemotherapy (n = 136). The overall median progression free survival time of first rescue protocol was 56.0 days (0–455 days). Important prognostic factors identified for first rescue protocol included the attainment of a complete response to the first rescue chemotherapy (p <.001), the use of a CHOP‐like first rescue protocol (p =.009), duration of first remission (HR 0.997, p =.028), and if prednisolone was included in the first rescue protocol (HR 0.41, p =.003). Adverse events (AE) were common, with 81.1% of dogs experiencing at least one AE during first rescue chemotherapy. This study highlights the need for improved first rescue therapies to provide durable remission in canine resistant or relapsed lymphoma. [ABSTRACT FROM AUTHOR]

Specific data regarding outcome of cats with high‐grade and large granular lymphocyte alimentary lymphoma (HGAL and LGL, respectively) treated with multi‐agent chemotherapy are scarce. The aims of this multi‐centric, retrospective study were to describe the outcome of cats with HGAL and LGL treated with COP‐ or CHOP‐based chemotherapy and to identify potential prognostic factors. Cats with a cytological or histological diagnosis of HGAL or LGL lymphoma treated with COP‐ or CHOP‐based protocol as first‐line chemotherapy were included. Data regarding diagnosis, staging, treatment and follow‐up were collected. Fifty‐seven cats treated with CHOP (n = 37) or COP (n = 20) protocols were included. Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 20%, 22%, 36% and 22% of cats, respectively, for an overall response rate of 42%. Median progression‐free interval (PFI) was 148 days and overall median survival time (OST) was 131 days. Cats achieving CR, PR or SD showed significantly longer PFI (p <.01) and OST (p <.015) compared with cats with PD. Other positive prognostic factors in multi‐variate analysis were rescue treatment (p <.001) and absence of lymph node involvement (p <.03). Negative prognostic factors were diffuse infiltration of the gastrointestinal tract (p =.035) and infiltration of a non‐haematopoietic organ (p <.01). [ABSTRACT FROM AUTHOR]

Canine lymphoma is a disease with high morbidity and poor long‐term prognosis, despite a high response rate to chemotherapy. In this study, we focused on liquid biopsy, in which small amounts of substances from body fluids were analysed, to determine whether cell‐free DNA (cfDNA) in the plasma can be used as a biomarker for lymphoma in dogs. We found that 23 patients with lymphoma had significantly higher cfDNA concentrations than the 12 healthy dogs (median 2360 ng/mL versus 299 ng/mL, p <.0001). Polymerase chain reaction for antigen receptor rearrangement (PARR) was also employed using cfDNA from the lymphoma group to investigate whether cfDNA could be used for the detection of genetic clonality of lymphomas, as well as the genomic DNA (gDNA) extracted from an original lesion in each case. The correlation of the PARR results between cfDNA and gDNA was observed in 100% of B‐cell lymphomas (10/10), 77.8% of T‐cell lymphomas (7/9), and 100% of other types of lymphomas (4/4), respectively. These results indicate that plasma cfDNA levels are increasing in canine lymphoma patients, that cfDNA concentration can be a novel diagnostic tool, and that it can be used as a diagnostic tool for PARR. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic stem cell transplantation (allo‐HSCT) is the only curative therapy for adult T‐cell leukaemia/lymphoma (ATL). Specific HLAs are associated with outcomes of immunotherapy and allo‐HSCT. We hypothesised that individual HLAs would affect the clinical outcomes of ATL patients after allo‐HSCT. Using data from a Japanese registry, we retrospectively analysed 829 patients with ATL who received transplants from HLA‐identical sibling donors or HLA‐A, ‐B, ‐C or ‐DRB1 allele‐matched unrelated donors between 1996 and 2015. We evaluated the overall mortality risk of HLA‐A, ‐B and ‐DR antigens with frequencies exceeding 3%. Outcomes were compared between transplants with or without specific HLA antigens. Of the 25 HLAs, two candidates were identified but showed no statistically significant differences by multiple comparison. HLA‐B62 was associated with a lower risk of mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI]: 0.51–0.90; p = 0.008), whereas HLA‐B60 was associated with a higher risk of mortality (HR, 1.64; 95% CI: 1.19–2.27; p = 0.003). In addition, HLA‐B62 was associated with a lower risk of transplant‐related mortality (TRM) (HR, 0.52; 95% CI: 0.32–0.85, p = 0.009), whereas HLA‐B60 was associated with a higher risk of grades III–IV acute graft‐versus‐host disease (HR, 2.63; 95% CI: 1.62–4.27; p < 0.001). Neither HLA influenced relapse. The higher risk of acute GVHD in HLA‐B60‐positive patients and the lower risk of TRM in HLA‐B62‐positive patients were consistent with previously obtained results from patients with other haematological malignancies. Consideration of HLA in ATL patients may help to predict risk and outcomes after allo‐HSCT. [ABSTRACT FROM AUTHOR]

Although several promising approaches for the treatment of relapsed/refractory diffuse large B‐cell lymphoma (rrDLBCL) have been approved recently, it remains unclear which patients will ultimately achieve long‐term responses. Circulating tumor (ct)DNA sequencing has emerged as a valuable tool to assess minimal residual disease (MRD). Correlations between MRD and outcomes have been shown in previously untreated DLBCL, but data on the repeated assessment of MRD in the dynamic course of rrDLBCL is limited. Here, we present an approach leveraging cost‐ and time‐sensitivity of digital droplet (dd)PCR to repeatedly assess MRD in rrDLBCL and present proof‐of‐principle for its ability to predict outcomes. [ABSTRACT FROM AUTHOR]

Nodal T‐follicular helper cell lymphoma (TFHL) is a subset of T‐cell lymphoma and frequently co‐occurs with Epstein–Barr virus (EBV)‐positive B‐cell lymphoma but not with T/NK‐cell lymphoma. Recently, a new entity with a worse prognosis, called EBV‐positive nodal T/NK‐cell lymphoma (NTNKL) has been established. Here, we report an autopsy case of synchronous multiple lymphomas, including TFHL and NTNKL. The patient was a 78‐year‐old female admitted with pneumonia. Although pneumonic symptoms were improved, fever, pancytopenia, and disseminated intravascular coagulation emerged, implicating lymphoma. She died on the 21st hospital day without a definitive diagnosis. The autopsy revealed the enlargement of multiple lymph nodes throughout her body. Histological analysis revealed three distinct regions in the left inguinal lymph node. The first region consists of small‐sized lymphocytes with T‐follicular helper phenotype and extended follicular dendritic cell meshwork, indicating TFHL. The second region included EBV‐positive large B cells. The third region comprised EBV‐positive large cells with cytotoxic T/NK cell phenotype, indicating NTNKL. Clonality analysis of the first and the third regions showed different patterns. Since various hematopoietic malignancies progress from common clonal hematopoiesis according to existing literature, this case may help to understand TFHL and NTNKL. [ABSTRACT FROM AUTHOR]

Objective: Cancer clinical trials (CCTs) provide access to emerging therapies and extra clinical care. We aimed to describe the volume and characteristics of CCTs available across Victoria, Australia, and identify factors associated with rural trial location. Methods: Quantitative analysis of secondary data from Cancer Council Victoria's Clinical Trials Management Scheme dataset. Design: A cross‐sectional study design was used. Setting: CCTs were available Victoria‐wide in 2018. Participants: There were 1669 CCTs and 5909 CCT participants. Main Outcome Measures: Rural CCT location was assessed as a binary variable with categories of 'yes' (modified Monash [MM] categories 2–7) and 'no' (MM category 1). MM categories were determined from postcodes. The highest ('least rural') MM category was used for postcodes with multiple MM categories. Results: Of 1669 CCTs, 168 (10.1%) were conducted in rural areas. Of 5909 CCT participants, 315 (5.3%) participated in rural CCTs. There were 526 CCTs (31.5%) with 1907 (32.3%) newly enrolled participants. Of 1892 newly enrolled participants with postcode data, 488 (25.8%) were rural residents. Of them, 368 (75.4%) participated in metropolitan CCTs. In a multivariable logistic regression analysis for all 1669 CCTs, odds of a rural rather than metropolitan CCT location were significantly (p‐value <0.05) lower for early‐phase than late‐phase trials and non‐solid than solid tumour trials but significantly (p‐value <0.05) higher for non‐industry than industry‐sponsored trials. Conclusions: In Victoria, 10% of CCTs are at rural sites. Most rural‐residing CCT participants travel to metropolitan sites, where there are more late‐phase, non‐solid‐tumour and industry‐sponsored trials. Approaches to increase the volume and variety of rural CCTs should be considered. [ABSTRACT FROM AUTHOR]

This article discusses a study on double expressor lymphoma (DEL) subtypes and the therapeutic mechanism of epigenetic agents. The study identified three subtypes of DEL with unique characteristics and found that DEL had an inferior survival compared to double negative lymphoma (DNL). The subtypes of DEL were associated with different cell-of-origin and genetic classifications. The study also analyzed the effects of tucidinostat and doxorubicin treatment on different oncogenic transcriptional factors and signaling networks in these subtypes. The results showed distinct molecular heterogeneity and a complex tumor microenvironment in DEL, which contribute to resistance to standard treatment. However, tucidinostat plus doxorubicin demonstrated broad-spectrum sensitivity in vitro and in vivo. The study provides insights for optimizing current treatment paradigms in DEL. [Extracted from the article]

Lymphoma is one of the most common malignant neoplasms in cats. Historically, most feline lymphomas were associated with feline leukaemia virus infection, but due to routine vaccination against the virus, especially in developed countries, feline leukaemia virus‐associated cases are dramatically reduced in numbers. More recently, the most common lymphoma in cats is intestinal lymphoma, with most common type being the enteropathy‐associated T‐cell lymphomas. Follicular lymphoma is recognised in cats, but is very uncommon. Primary colorectal follicular lymphoma is rare in humans and has been reported in three dogs. In this case report, we describe a primary colorectal lymphoma with histological and immunohistochemical features of a follicular lymphoma in a Savannah cat. To the authors' knowledge, this is the first case report of a primary colorectal follicular lymphoma in cats, and differential diagnosis of tumours in the colorectal area in cats should include follicular lymphoma. [ABSTRACT FROM AUTHOR]

Given the significant limitations of available literature, central nervous system (CNS) prophylaxis in large B‐cell lymphomas remains debatable. Wilson and colleagues provide cautious recommendations, on a case‐by‐case basis, useful to guide discussion with individual patient. In daily practice, CNS relapse risk, prophylaxis safety and prognosis of CNS recurrence must be considered.Commentary on: Wilson et al. Central nervous system prophylaxis in large B‐cell lymphoma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19686. [ABSTRACT FROM AUTHOR]

Bispecific antibodies have shown significant clinical efficacy in patients with relapsed/refractory B‐cell non‐Hodgkin lymphomas and multiple myeloma, expanding treatment options for these patients. While these advancements are promising, it is important to be aware of associated side effects, such as cytokine release syndrome, neutropenia and infections. Gonugunta et al. provide valuable insights into the infection risks linked to the use of bispecific antibodies in haematological malignancies, drawing on both clinical trial data and real‐world experiences. Commentary on: Gonugunta et al. Risk of infections with bispecific antibodies in B‐cell non‐Hodgkin lymphomas and multiple myeloma—The current state. Br J Haematol 2024; 205:1197‐1201. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non‐Hodgkin's lymphoma (NHL), especially B‐cell non‐Hodgkin's lymphoma (B‐NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. Methods: The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression‐free survival (PFS), and overall survival (OS) of HBV‐positive and negative B‐NHL subtypes were compared according to HBV infection. Results: The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B‐NHL was higher than that in the T‐cell non‐Hodgkin's lymphoma (T‐NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B‐NHL was similar to that of the indolent B‐NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B‐cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV‐positive and negative patients in the two subtypes. Conclusions: There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B‐NHL, but not T‐NHL. [ABSTRACT FROM AUTHOR]

Summary: Peripheral T‐cell lymphomas (PTCL) are morphologically and biologically heterogeneous and a subset expresses CD30, including anaplastic large cell lymphomas (ALCL) and a minority of PTCL, not otherwise specified (PTCL, NOS). ALCL with ALK translocations (ALCL, ALK+) are readily identified by routine diagnostic methods, but differentiating ALCL without ALK translocation (ALCL, ALK−) and PTCL, NOS expressing CD30 (PTCL CD30+) can be challenging. Furthermore, rare PTCL co‐express CD30 and CD15 (PTCL CD30+CD15+); some resemble ALCL, ALK− while others resemble classic Hodgkin lymphoma. To explore the relationship between PTCL CD30+CD15+ and ALCL, ALK−, we analysed 19 cases of PTCL with CD30 expression, previously diagnosed as ALCL, ALK− (nine cases) and PTCL CD30+CD15+ (10 cases) for DUSP22/IRF4 rearrangements, coding RNA expression and selected transcriptome analysis using the NanoString nCounter gene expression analysis platform. Unsupervised clustering showed no clear segregation between ALCL, ALK− and PTCL CD30+CD15+. Three cases previously classified as PTCL CD30+CD15+ showed DUSP22/IRF4 rearrangements, favouring a diagnosis of ALCL, ALK−. Our results suggest that cases previously designated PTCL CD30+CD15+, likely fall within the spectrum of ALCL, ALK−; additionally, a subset of ALCL, ALK− with DUSP22/IRF4 rearrangement expresses CD15, consistent with previous reports and expands the immunophenotypic spectrum of this lymphoma subgroup. [ABSTRACT FROM AUTHOR]