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The House of Commons Standing Committee on Health proposed in 2022 to start a national registry for breast implants. Why, and what requirements are needed, will be outlined. Breast implant products are not always in compliance with international norms and standards, and several scandals have occurred because of industry fraud. To trace which patients have defective breast implants, a good registry is an absolute must. Furthermore, some diseases, such as lymphomas, autoimmune diseases, and so-called breast implant illness, are believed to be associated with breast implants. An accurate estimation of how often these diseases occur in patients with breast implants is lacking. A registry in which not only surgical data but also patient-reported outcome measurements are recorded will result in a better understanding of patient outcomes and device performance. The registry should not be a voluntary ('opt-in') registry but a mandatory ('opt-out') registry, in which only the patient (and not the surgeon) has the choice whether to participate., It is estimated that 3%-4% of women in Western countries have silicone breast implants. Of these, 70% are placed for cosmetic reasons, whereas about 30% are placed for reconstruction after [...]

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]

Herein, we report a case of a 16-year-old girl who presented with an episode of shortness of breath while playing sports. Upon radiologic workup, she was found to have a large multicystic anterior mediastinal mass. The cystic appearance of mass and lack of constitutional symptoms contributed to favoring a benign cystic process and deferring surgical resection until the end of sport season. When surgery was performed 3 months later, microscopic examination showed findings diagnostic of classic Hodgkin lymphoma arising in a thymic cyst. Despite the rarity of such cases, it is important to remember that the cystic nature of an anterior mediastinal mass does not exclude lymphoma. Definitive diagnosis is not possible without examination of representative tissue. [ABSTRACT FROM AUTHOR]

Background: India is a vast and diverse country with existing variations in the frequency and distribution of cancers across its various parts. In regions lacking population-based cancer registries (PBCRs) in a vast country like India, hospital-based cancer registry (HBCR) data become an important source of information on the trends and patterns of a region. To determine the numerical trends of cases of the top ten cancer sites reporting to HBCR of a tertiary care cancer center in Bihar from 2014 to 2021. Materials and Methods: The details of all histopathologically confirmed cancer cases registered in the HBCR department of radiation oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, India between January 2014 and December 2021 were included in this retrospective observational study. All these cases were grouped site-wise and listed in descending order of the total number of cases reported in each group. Cross-tabulation with age and sex distribution was done. The frequency distribution of the top ten leading cancers for every consecutive calendar year was plotted in line diagrams for time trend analysis. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.). was used for analysis. Annual percent change (APC) was determined for the number of cases of all ten cancer sites using joinpoint regression analysis (Joinpoint Regression Software, Version 4.0.4--May 2013; Statistical Methodology and Applications Branch, Surveillance Research Program of the US National Cancer Institute; Bethesda, MD, USA). Results: Out of 32,057 total cancer cases registered between Jan 2014 and Dec 2021, 21,848 patients (68.2%) cases constituted the top ten cancers. The top ten cancers among both sexes were cancer gallbladder (n = 4204, 13.1%), head and neck (n = 3395, 10.6%), breast (n = 3392, 10.6%), lung (n = 2069, 6.5%), cervix (n = 2039, 6.4%), hematolymphoid (n = 1930, 6.0%), liver (n = 1572, 4.9%), stomach (n = 1116, 3.5%), ovary (n = 1103, 3.4%), and colon-rectum (n = 1028, 3.2%). Except for cervical and hematolymphoid cancers, the rest all showed a rising trend over consecutive years. Conclusion: Cancer of the gallbladder continues to be among the most common cancers in the region. Focused research in all aspects of this deadly disease is needed. Strengthening of prevention and screening programs for common cancers and upliftment of the existing infrastructure for diagnosis and treatment of cancer in the region are necessitated. [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]

Higher suicide rates were observed in patients diagnosed with lymphoma. In this study, we accurately identified patients with high-risk lymphoma for suicide by constructing a nomogram with a view to effective interventions and reducing the risk of suicide. 235,806 patients diagnosed with lymphoma between 2000 and 2020 were picked from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training (N = 165,064) and validation set (N = 70,742). A combination of the Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression identified the predictors that constructed the nomogram. To assess the discrimination, calibration, clinical applicability, and generalization of this nomogram, we implemented receiver operating characteristic curves (ROC), calibration curves, decision curve analysis (DCA), and internal validation. The robustness of the results was assessed by the competing risks regression model. Age at diagnosis, gender, ethnicity, marital status, stage, surgery, radiotherapy, and annual household income were key predictors of suicide in lymphoma patients. A nomogram was created to visualize the risk of suicide after a lymphoma diagnosis. The c-index for the training set was 0.773, and the validation set was 0.777. The calibration curve for the nomogram fitted well with the diagonal and the clinical decision curve indicated its clinical benefit. The effects of unmeasured and unnoticed biases and confounders were difficult to eliminate due to retrospective studies. A convenient and reliable model has been constructed that will help to individualize and accurately quantify the risk of suicide in patients diagnosed with lymphoma. • Combining the results of lasso regression and Cox proportional hazards regression to filter predictors. • A suicide nomogram was developed with good performance by utilizing common but significant indictors. • The Fine and Gray competing risks model validated the robustness of this study. [ABSTRACT FROM AUTHOR]

Context.--Posttransplant lymphoproliferative disorder (PTLD) remains a significant complication in pediatric patients undergoing solid organ transplant (SOT). The majority involve Epstein-Barr virus (EBV)-driven CD20+ B-cell proliferations, which respond to reduction of immuno-suppression and anti-CD20-directed immunotherapy. Owing to the low overall incidence, prospective studies of pediatric PTLD are scarce, leading to a lack of comprehensive under-standing of this disorder in pediatric populations. This review aims to bridge this knowledge gap by providing a comprehensive analysis of the clinical, morphologic, and molecular genetic features of PTLD in children, adolescents, and young adults after SOT. Objective.--To examine the clinical features, pathogenesis, and classification of pediatric PTLDs after SOT. Data Sources.--Personal experiences and published works in PubMed. Conclusions.--PTLD includes a broad and heterogeneous spectrum of disorders, ranging from nonmalignant lympho- proliferations to lymphomas. While most pediatric PTLDs are EBV+, an increasing number of EBV- PTLDs have been recognized. The pathologic classification of PTLDs has evolved in recent decades, reflecting advancements in understanding the underlying pathobiology. Nevertheless, there remains a great need for further research to elucidate the biology, identify patients at higher risk for aggressive dis-ease, and establish optimal treatment strategies for relapsed/ refractory disease. [ABSTRACT FROM AUTHOR]

Statement of the Problem: Chemotherapy-induced mucositis is the most common complication during cancer treatment. This complication can lead to pain, increased risk of infection and malnutrition. Therefore, it is important to find a solution to reduce the severity and duration of side effects. Purpose: This study aimed to assess the efficacy of Mucosamin spray as an adjunct for prevention of oral mucositis in children under chemotherapy. Materials and Method: This parallel-design clinical trial evaluated 48 patients aged 5 to 15 years with leukemia and lymphoma presenting to the Hematology Department of Mofid and Mahak Hospitals. The patients were randomly divided into two groups (n=24). Before starting chemotherapy, all patients received oral hygiene instructions (toothbrushing without flossing). Patients in both groups were requested to use a mouthwash composed of nystatin, aluminum-magnesium hydroxide suspension (aluminum MgS), and diphenhydramine for 1 min every morning on a daily basis starting the day before treatment. Patients in the intervention group were also requested to spray their entire oral mucosa with Mucosamin spray 3 times a day in addition to using the mouthwash. Patients were requested to refrain from eating and drinking for 1h after spraying. The patients were clinically examined by a senior dental student once every other day for 20 days regarding the occurrence, severity, and duration of oral mucositis. Data were analyzed using the Chi-square and Mann-Whitney tests, Kaplan-Meier survival analysis, and log rank test. Results: No significant difference was noted between the two groups in the incidence, severity, or time of development of mucositis (p> 0.05). The 7-day non-recovery percentage was 72.7% (SE= 13.4) and 25.0% (SE= 15.3) in the control and test groups, respectively, indicating shorter duration (faster healing) of mucositis in the intervention group (p= 0.01). Conclusion: Within the limitations of this study, it seems that prophylactic application of Mucosamin spray can shorten the course of oral mucositis, in case of its occurrence. [ABSTRACT FROM AUTHOR]

Lymphoma is a highly heterogeneous lymphohematopoietic tumor. As our understanding of the biological and pathological characteristics of lymphoma improves, we are identifying an increasing number of lymphoma subtypes. Genotyping has enhanced our ability to diagnose, treat, and monitor the prognosis of lymphoma. Despite significant improvements in treatment effectiveness, traditional methods for assessing disease response and monitoring prognosis are imperfect, and there is no significant improvement in overall remission rates for lymphoma patients. Minimal Residual Disease (MRD) is often indicative of refractory disease or early relapse. For lymphoma patients, personalized MRD monitoring techniques offer an efficient means to estimate disease remission levels, predict early relapse risk, and assess the effectiveness of new drug regimens. In this review, we delve into the MRD procedures in lymphoma, including sample selection and requirements, detection methods and their limitations and advantages, result interpretation. Besides, we also introduce the clinical applications of MRD detection in lymphoma. [ABSTRACT FROM AUTHOR]

Approximately 80% of pediatric tumors occur in low- and middle-income countries (LMIC), where diagnostic tools essential for treatment decisions are often unavailable or incomplete. Development of cost-effective molecular diagnostics will help bridge the cancer diagnostic gap and ultimately improve pediatric cancer outcomes in LMIC settings. We investigated the feasibility of using nanopore whole transcriptome sequencing on formalin-fixed paraffin embedded (FFPE)-derived RNA and a composite machine learning model for pediatric solid tumor diagnosis. Transcriptome cDNA sequencing was performed on a heterogenous set of 221 FFPE and 32 fresh frozen pediatric solid tumor and lymphoma specimens on Oxford Nanopore Technologies' sequencing platforms. A composite machine learning model was then used to classify transcriptional profiles into clinically actionable tumor types and subtypes. In total, 95.6% and 89.7% of pediatric solid tumors and lymphoma specimens were correctly classified, respectively. 71.5% of pediatric solid tumors had prediction probabilities > 0.8 and were classified with 100% accuracy. Similarly, for lymphomas, 72.4% of samples that had prediction probabilities > 0.6 were classified with 97.6% accuracy. Additionally, FOXO1 fusion status was predicted accurately for 97.4% of rhabdomyosarcomas and MYCN amplification was predicted with 88% accuracy in neuroblastoma. Whole transcriptome sequencing from FFPE-derived pediatric solid tumor and lymphoma samples has the potential to provide clinical classification of both tissue lineage and core genomic classification. Further expansion, refinement, and validation of this approach is necessary to explore whether this technology could be part of the solution of addressing the diagnostic limitations in LMIC. [ABSTRACT FROM AUTHOR]

Background: The histopathological classification of T-cell lymphoma (TCL) in humans has distinctive mutational genotyping that suggests different lymphomagenesis. A similar concept is assumed to be observed in dogs with different TCL phenotypes. Objective: This study aimed to identify the previously reported single-nucleotide polymorphisms (SNPs) in both human beings and dogs in canine TCLs and nullcell lymphomas (NCLs) and to design compatible oligonucleotides from each variant based on the multiplex polymerase chain reaction. Methods: Genomic DNA was extracted from 68 tumor specimens (62 TCLs and 6 NCLs) and 5 buffy coat samples from dogs with TCL. Four TCL subtypes and NCL were analyzed in 44 SNPs from 21 genes using the MassARRAY. Results: The greatest incidences of SNPs observed in all TCL subtypes and NCL ware SATB1 c.1259A > C, KIT c.1275A > G, SEL1L c.2040 + 200C > G, and TP53 c.1024C > T, respectively. Some SNP locations were statistically significant associated with NCL, including MYC p.S75F (p = 0.0003), TP53 p.I149N (p = 0.030), PDCD1 p.F37LX (p = 0.012), and POT1 p.R583* (p = 0.012). Conclusion: Each TCL histological subtype and NCL are likely to contain distinctive mutational genetic profiles, which might play a role in lymphoma gene-risk factors and might be useful for selecting therapeutic target drugs for each canine patient. [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology Background: Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a recently described malignant lymphoma that presents with serous effusions in the pleura, peritoneum, and/or pericardium but without an identifiable lymphoma mass. This report describes the case of an 80-year-old man who presented with a pleural effusion and describes the approach to diagnosis and management of FO-LBCL. Case Report: We present a case of an 80-year-old man who presented with right pleural effusion and shortness of breath at work. Initial radiological assessment suggested a pleural effusion on the right side, without an identifiable mass, given the patient’s symptoms and imaging characteristics. Subsequently, he underwent a pleural fluid puncture and biopsy. Based on the initial pathological assessment, malignant lymphoma, a non-epithelial tumor, was considered likely, but differentiation from reactive proliferative cells was difficult, given the patient’s symptoms and cytologic characteristics. Postoperatively, histopathological examination and immunohistochemistry confirmed a diagnosis of FO-LBCL. After 1 year of follow-up, the condition had progressed and the patient died due to recurrence. Conclusions: This report has presented a case of FO-LBCL in an elderly man with pleural effusion and described how this rare and recently described lymphoma was diagnosed and managed. [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]

AbstractAnalytes within liquid biopsies have emerged as promising alternatives to traditional tissue biopsies for various malignancies, including lymphomas. This review explores the clinical applications of one such liquid biopsy analyte, circulating tumor DNA (ctDNA) in different types of lymphoma, focusing on its role in diagnosis, disease monitoring, and relapse detection. Advancements in next-generation sequencing (NGS) and machine learning have enhanced ctDNA analysis, offering a multi-omic approach to understanding tumor genetics. In lymphoma, ctDNA provides insights into tumor heterogeneity, aids in genetic profiling, and predicts treatment response. Recent studies demonstrate the prognostic value of ctDNA and its potential to improve patient outcomes by facilitating early disease detection and personalized treatment strategies Despite these advancements, challenges remain in optimizing sample collection, processing, assay sensitivity, and overall consensus workflows in order to facilitate integration into routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: Ataxia-telangiectasia (A-T) is a rare autosomal recessive multi-system and life-shortening disease, characterized by progressive cerebellar neurodegeneration, immunodeficiency, radiation sensitivity and cancer predisposition, with high incidence of leukemia and lymphoma. A-T is caused by mutations in the gene encoding for ATM protein that has a major role in maintaining the integrity of the genome. Because there are no cures for A-T, we aimed to tackle immunodeficiency and prevent cancer onset/progression by transplantation therapy. Methods: Enriched hematopoietic stem/progenitor cells (HSPCs), collected from bone marrow of wild-type mice, were transplanted in the caudal vein of 1 month old conditioned Atm−/− mice. Results: Genomic analyses showed that transplanted Atm positive cells were found in lymphoid organs. B cells isolated from spleen of transplanted mice were able to undergo class switching recombination. Thymocytes were capable to correctly differentiate and consequently an increase of helper T cells and TCRβhi expressing cells was observed. Protein analysis of isolated T and B cells from transplanted mice, revealed that they expressed Atm and responded to DNA damage by initiating an Atm-dependent phosphorylation cascade. Indeed, aberrant metaphases were reduced in transplanted Atm-deficient mice. Six months after transplantation, Atm−/− mice showed signs of aging, but they maintained the rescue of T cells maturation, showed DNA damage response, and prevented thymoma. Conclusion: We can conclude that wild-type enriched HSPCs transplantation into young Atm-deficient mice can ameliorate A-T hematopoietic phenotypes and prevent tumor of hematopoietic origin. [ABSTRACT FROM AUTHOR]

Double hit lymphoma (DHL) and double-expressor lymphoma (DEL) are now considered as aggressive types of diffuse large B cell lymphoma. DHL is characterized by a dual rearrangement of MYC and B cell lymphoma 2 (BCL-2) and/or B cell lymphoma 6 (BCL-6) and DEL by overexpression of MYC and BCL-2. Both DHL and DEL have aggressive presentation and are more common in elderly population. We present a case of 1 ½ years old boy who presented with bilateral proptosis, and diagnosed as non-Hodgkin lymphoma with central nervous system involvement. Immunohistochemistry revealed high expression of MYC and BCL-2. Fluorescence in situ hybridization studies done to rule out DHL showed no translocation of C-MYC, Bcl-2, and Bcl-6 and hence were confirmed as double-expressor high-grade B cell lymphoma. Dual expression of C- MYC, Bcl-2, or Bcl-6 always needs further evaluation to rule out the more aggressive DHL subtypes. [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]

Lymphomas are a diverse group of neoplastic disorders arising primarily in lymph nodes. They have been majorly classified into Hodgkin and Non-Hodgkin lymphomas(NHL). NHL can be of B, T and Null cell categories having further subtypes based on their histological characteristics. Lymphomas can be nodal and extra nodal. The head and neck area are the second most common site of extra nodal lymphoma, with tonsils being the most common site of involvement; other sites include the nasopharynx and tongue base. B- Cell type being the most common type. Predominantly occurs in elderly. Presentations depends on the site involved. Various modalities like surgical treatment, chemotherapy (or) radiotherapy is available. Each stage has varied survival rates and prognosis and responses to the treat depending on the patient factors. In this paper, we report two cases of patients with non-Hodgkin lymphoma of tonsil, where the preoperative clinical diagnosis and radiological diagnosis was inconclusive and final diagnosis was established based on histopathological examination. [ABSTRACT FROM AUTHOR]

Primary lymphoma of bone (PLB) is a rare, malignant lymphoid proliferation within bone accounting for less than 3% of all malignant bone tumors. In this case report, a 61-year-old female with past medical history of gout presented with pain and swelling in her right little finger. Initial radiographs demonstrated periostitis and soft tissue swelling about the right little finger. She returned three months later with progressive pain. Subsequent MRI and repeat radiographs demonstrated near complete destruction of the right little finger middle phalanx and periostitis with marrow infiltration at the right long finger. Given the rapid progression of disease, the differential diagnosis consisted primarily of aggressive neoplastic processes. The little finger ray was amputated through the level of the metacarpophalangeal joint and histopathology demonstrated large neoplastic cells that stained positive with CD45, CD20, and PAX5, compatible with diffuse large B-cell lymphoma. A subsequent normal bone marrow aspiration and PET-CT demonstrated no additional sites of disease, thus excluding secondary lymphoma to bone. To the best of our knowledge, this is the first case report of polyostotic PLB involving the hand. PLB of the hands may be initially misdiagnosed due to its rarity and clinical presentation mimicking rheumatological disease. Clinical vigilance in concert with close imaging follow-up is required to make the diagnosis in a timely fashion. We also review the existing PLB hand literature which consists of five cases. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored the prognostic significance of the pontine-white matter (PW) score in primary central nervous system (CNS) lymphoma patients with post-treatment 18F-FDG PET/CT and PET/MR imaging. Eligible patients were enrolled from January 2014 to December 2022. The PW score, derived from FDG uptake of the pons and white matter, was used to evaluate the metabolic activity of the treated lesion and its prognostic implications. A total of 90 patients across PET/CT and PET/MR modalities were assessed. The PW score demonstrated a robust discriminative ability in identifying patients with worse outcomes. It was also found to be a significant and independent indicator for worse prognosis in both PET/CT and PET/MR groups. The study demonstrated that this novel internal standardization indicator was an effective tool for risk stratification in primary CNS lymphoma post-treatment scenarios. Background: Limited data exist on the significance of PET imaging and quantitative PET parameters in primary central nervous system (CNS) lymphoma due to its relative rarity. This study was conducted to investigate the prognostic value of a novel internal standardization indicator, the pontine-white matter (PW) score, in primary CNS lymphoma patients undergoing post-treatment 18F-FDG PET/CT and PET/MR imaging. Methods: From January 2014 to December 2022, eligible patients with primary CNS lymphoma who underwent post-treatment PET imaging were enrolled. Using the FDG uptake of the pons and white matter as an internal reference, the PW score was graded based on the metabolism of the post-therapeutic lesion for each patient, and its associations with patients' prognosis were investigated. Results: In total, 41 patients with post-treatment PET/CT and 49 patients with post-treatment PET/MR imaging were enrolled. ROC curve analysis indicated that the PW score possessed robust discriminative ability in distinguishing patients with worse outcomes. Furthermore, a higher PW score was significantly correlated with and identified as an independent prognostic indicator for, worse prognosis in both the PET/CT and PET/MR cohorts. Conclusion: The study demonstrated that the PW score was an effective prognostic indicator for identifying post-treatment primary CNS lymphoma patients with worse outcomes. [ABSTRACT FROM AUTHOR]

Neurolymphomatosis (NL) describes an infiltration of cranial and peripheral nerves by lymphoma cells, most frequently in non-Hodgkin B-cell lymphoma. This clinical entity is rare and poses a challenging diagnosis. We describe a case of a 64-year-old female patient with NL associated with extra-nodal NK/T-cell lymphoma (ENKTL), nasal type, presenting as a painful progressive mononeuropathy multiplex with an oral cavity lesion. ENKTL is usually associated with Epstein-Barr virus (EBV) infection and rarely affects the central and peripheral nervous system. Lumbar puncture, magnetic resonance imaging (MRI), nerve biopsy, and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) help to establish the diagnosis. Thereby, NL should be considered in the differential diagnosis of painful progressive multiple neuropathies, even in patients without previous history of cancer. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive lymphoma entirely localized in the central nervous system or vitreoretinal space. PCNSL generally initially responds to methotrexate-containing chemotherapy regimens, but progressive or relapsing disease is common, and the prognosis is poor for relapsed or refractory (R/R) patients. PCNSL is often characterized by activation of nuclear factor kappa B (NF-κB) due to mutations in the B-cell receptor (BCR) or toll-like receptor (TLR) pathways, as well as immune evasion. Targeted treatments that inhibit key PCNSL mechanisms and pathways are being evaluated; inhibition of Bruton's tyrosine kinase (BTK) downstream of BCR activation has demonstrated promising results in treating R/R disease. This review will summarize the evidence and potential for targeted therapeutic agents to improve treatment outcomes in PCNSL. This includes immunotherapeutic and immunomodulatory approaches and inhibitors of the key pathways driving PCNSL, such as aberrant BCR and TLR signaling. [ABSTRACT FROM AUTHOR]

MALT lymphoma is a commonly encountered orbital tumor, and primary amyloidosis is frequently found to be an independent orbital lesion. Orbital MALT lymphoma with associated amyloid deposition is considered rare, with only 12 cases previously published. We describe a 33-year-old man, the youngest patient reported to-date, with a mass in the superonasal quadrant of the right anterior orbit. Pathology demonstrated extranodal marginal zone lymphoma in mucosa-associated lymphoid tissue with associated amyloid deposition. Systemic work-up revealed no other site of either lymphoma or amyloidosis. The patient underwent local irradiation and subsequent surgical resection of the residual mass. Persistent lymphoma was found and treated with rituximab. [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]

To investigate lacrimal gland malignancies' incidence and survival rates in the USA between 1995 and 2018. Incidence and survival data from the North American Association of Central Cancer Registries of lacrimal gland malignancies between 1996 and 2018 were extracted and analyzed. This study analyzed data pertaining to 3620 patients (females 56.7%, n = 2051). A sizable number of patients were 60–79 years of age (45.1%, n = 1633), with a substantial majority being of the non-Hispanic white ethnicity (82.9%, n = 3002). A little above half of patients (52.1%, n = 1886) had presented with a localized disease. Lymphomas represented 59.3% (n = 2146) of lacrimal gland malignancies, while 37% (n = 1339) were carcinomas. The cumulative age-adjusted incidence rate per million was 0.53 for all malignancies, 0.31 for lymphomas, and 0.2 for carcinomas. While the annual crude incidence rate showed a significant steady increase (average annual change of 1.24%; P <.05), age-adjusted rates did not show a similar trend. The five- and 10-year relative survival rates were 88.64 months (95% confidence interval (CI): 85.81–90.93) and 80.26 months (95%CI: 76.21–83.7), respectively. Older age, non-lymphoma tumors, and advanced stage at diagnosis were significantly associated with worse outcomes. Relative survival rates did not show significant changes from 1995 to 2018, irrespective of gender, race or treatment received. Early detection and localized tumor management can improve survival outcomes for patients with lacrimal gland malignancies. Further research is needed to understand these malignancies' risk profiles and develop more effective treatment strategies. [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]

Background: The interaction between CD47 and signal-regulatory protein-alpha (SIRPα) inhibits phagocytosis, and their clinicopathological characteristics have been evaluated in various diseases. However, the significance of CD47 and SIRPα expression, as well as the combined effect, in Extranodal Natural killer/T-cell Lymphoma (ENKTL) remains uncertain. Methods: In total, 76 newly diagnosed ENKTL patients (mean age 49.9 years, 73.7% male) were included in this study. CD47 and SIRPα expression were examined by immunohistochemistry. Survival analyses were conducted through Kaplan-Meier curves and the Cox regression model. Results: Seventy-one (93.4%) cases were categorized as the CD47 positive group and 59 (77.6%) cases were categorized as the SIRPα positive group. CD47-negative cases had more advanced-stage illness (P = 0.001), while SIRPα-positive cases showed significantly lower levels of high-density lipoprotein (P < 0.001). In univariable analysis, CD47, SIRPα expression, and their combination were significantly associated with prognosis (P < 0.05). In multivariable analysis, only positive SIRPα expression remained significantly associated with superior overall survival (Hazard ratio [HR] 0.446; 95% confidence interval [CI] 0.207–0.963; P = 0.004). Furthermore, SIRPα expression could re-stratify the survival of patients in ECOG (< 2), advanced CA stage, PINK (HR), CD38-positive, PD1-positive, and CD30-positive groups. Conclusions: SIRPα status was a potential independent prognostic factor for ENKTL. The prognostic significance of CD47 expression and the interaction between CD47 and SIRPα in ENKTL need further investigation. [ABSTRACT FROM AUTHOR]

Chemokine ligand 13 (CXCL13) and its chemokine receptor 5 (CXCR5) both play significant roles in the tumor microenvironment (TME). CXCL13 in cerebrospinal fluid (CSF) has recently been found to have significant diagnostic and prognostic value in primary and secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL), and the CXCL13-CXCR5 axis has been shown to play an important chemotactic role in the TME of CNS-DLBCL. In this review, we first describe the clinical value of CXCL13 in CSF as a prognostic and diagnostic biomarker for CNS-DLBCL. In addition, this review also discusses the specific mechanisms associated with the CXCL13-CXCR5 axis in tumor immunity of primary diffuse large B cell lymphoma of the central nervous system (PCNS-DLBCL) by reviewing the specific mechanisms of this axis in the immune microenvironment of DLBCL and CNS inflammation, as well as the prospects for the use of CXCL13-CXCR5 axis in immunotherapy in PCNS-DLBCL. [ABSTRACT FROM AUTHOR]

Purpose: This single center retrospective study aimed to investigate the factors associated with central nervous system (CNS) involvement of primary vitreoretinal lymphoma (PVRL). Methods: Clinical features of patients with PVRL (Group 1), those diagnosed with vitreoretinal lymphoma (VRL) after primary CNS lymphoma diagnosis (Group 2), and those concurrently diagnosed with CNS lymphoma and VRL (Group 3), were compared. The main outcomes included sex, age, types of treatment, survival, visual acuity, diagnostic methods, VRL recurrence, ocular manifestations, and interleukin levels in the aqueous humor. Results: Groups 1, 2, and 3 included 66 eyes in 38 patients, 29 eyes in 18 patients, and 14 eyes in 8 patients, respectively. Group 3 had shorter overall survival (OS) than Groups 1 and 2 (P = 0.042 and P = 0.009, respectively). The three groups did not differ in progression-free survival (P = 0.060). The 5-year survival rates of Groups 1, 2, and 3 were 56.5%, 44.0%, and 25.0%, respectively (P = 0.001). Patients with CNS involvement in Group 1 exhibited VRL recurrence (P < 0.001), high interleukin-10 (P = 0.024), and sub-retinal pigment epithelium (RPE) infiltration (P = 0.009). Patients experiencing VRL recurrence in Group 1 tended to show CNS involvement (P < 0.001). Conclusion: Patients concurrently diagnosed with CNS lymphoma and VRL had a shorter OS and a lower 5-year survival rate. In patients with PVRL, the recurrence of VRL, high interleukin-10, and sub-RPE infiltration were associated with CNS involvement. [ABSTRACT FROM AUTHOR]

High upfront cost may be a barrier to adopting chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory B-cell lymphoma. Data on the real-world costs are limited. Using the Blue Cross Blue Shield Axis database, we evaluated 271 commercially insured patients who received CAR-T therapy for B-cell lymphoma (median age = 58 years; men = 68%; diffuse large B-cell lymphoma = 87%; inpatient CAR-T therapy = 85%). Our peri–CAR-T period of interest was from 41 days before to 154 days after CAR-T therapy index divided into seven 28-day intervals. Median total costs were $608 100 (interquartile range, IQR = $534 100-$732 800); 8.5% of patients had total costs exceeding $1 million. The median cost of CAR-T therapy products was $402 500, and the median out-of-pocket copayment was $510. Monthly costs were highest during the month of CAR-T therapy administration (median = $521 500), with median costs below $25 000 in all other 28-day intervals. Costs of CAR-T therapy use were substantial, largely driven by product acquisition. Future studies should examine the relationship between costs, access, and financial outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Randomized clinical trials (RCTs) have suggested that BTK inhibitors (BTKis) might increase infectious disease (ID) risk. Systematic analysis of this topic as derived from RCTs and clinical practice is needed. Areas covered: An extensive Medline, Embase, and Cochrane search of peer-reviewed sources reporting on ID morbidity in patients on BTKis was performed (1 January 2014 - 31 December 2013). Contribution of intrinsic immune defects in indolent B-cell lymphomas to this morbidity was carefully considered. Expert opinion: Patients with indolent B-cell lymphomas display a wide range of innate and adaptive immune defects. In addition, BTKi use is linked with an increased signal of upper respiratory tract infections (URTIs) and pneumonias, mainly grade 1–2. These agents also increase the risk of rare invasive fungal infections (IFIs), mainly due to Cryptococcus and Aspergillus spp. with a peak within several months after the start of therapy. More than half of these IFIs are fatal. Research suggests a similar ID risk across 1st, 2nd and 3rd generations of BTKis, all causing B-cell dysfunction due to BTK inhibition, along with off-target functional neutrophil/macrophage alterations. Expanding the knowledge base on ID morbidity in patients on BTKis would facilitate timely diagnosis and treatment, and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (ASCT) is a potentially curative strategy for relapse or refractory(r/r) aggressive lymphoma. However, a proportion of lymphoma patients who are at high risk of mobilization failure fail to mobilize stem cells and cannot proceed to ASCT. The aim of this study is to explore the efficacy and safety of Etoposide combined with Cytarabine (EA) plus G-CSF mobilization in poor mobilizers (PMs) with r/r aggressive lymphoma. Methods: This retrospective study analyzed the outcomes of chemomobilization based on EA (Etoposide 0.1 g/m2, qd d1~3; AraC 0.5 g/m2, q12h d1~3) in 98 patients with r/r aggressive lymphoma. Of these, 39 patients met the criteria for predicted PMs as proposed by the Gruppo Italiano Trapianto di Midollo Osseo working group. Results: Of the 39 PMs, 38(97.4%) patents harvested adequate mobilization (=2×106 CD34+ cells/kg), while 31(79.5%) patients achieved optimal mobilization (=5×106 CD34+ cells/kg). Overall, the mean number of CD34+ cells/kg collected was 17.99(range: 1.08~83.07) ×106 with an average of 1.4 apheresis sessions, and the number was 15.86(range: 0.37~83.07) ×106 for the first apheresis, respectively. A single apheresis procedure was sufficient to reach the target yield of adequate mobilization in 35(89.7%) PMs, while 76.9% of PMs achieved optimal collection within two apheresis sessions. We observed acceptable hematological toxicity and antibiotic usage exposure in 26 patients with a mean duration of 3.6 days. No grade 4 infection or mobilization-related mortality was recorded. Most patients underwent ASCT and achieved successful hematopoietic recovery with prompt engraftment duration, except for one NK/T-cell lymphoma patient who succumbed to severe septicemia after receiving conditioning chemotherapy. Conclusion: Our findings indicate that EA plus G-CSF is an effective and tolerable CD34+ stem cell mobilization strategy for patients with r/r lymphoma, including those predicted to be PMs. This regimen could be an option for patients with r/r lymphoma, particularly those undergoing mobilization for salvage ASCT therapy. [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]

Background: One of the main drawbacks of tunneled central venous catheters (CVCs) is catheter-related bloodstream infections (CRBSIs). Antibiotic lock therapy (ALT) can be combined with systemic antibiotics to achieve catheter salvage. Our objectives are to describe cases of CRBSI and our experience with ALT in a pediatric oncology–hematology ward. Methods: a retrospective descriptive study of pediatric CRBSI cases in a Spanish oncology–hematology unit from 2007 to 2017 was conducted. We collected demographic, clinical, and microbiological data from all patients. Results: fifty-eight CRBSIs were diagnosed in thirty-nine patients; 72.9% of these patients were male, with a median age of 42.1 months. The main underlying diseases were leukemia/lymphoma (51.7%) and solid tumors (32.7%). Thirty-five (60.3%) CRBSIs were caused by Gram-positive cocci, of which 70.6% were coagulase-negative Staphylococci, and sixteen (27.6%) were caused by Gram-negative bacilli. We treated 41/58 (71%) cases with ALT. A total of 12/17 (71%) CVCs that were not treated with adjunctive ALT were removed, compared with 13/41 (32%) that were treated with ALT (relative risk (RR), 0.449; confidence interval (CI), 95%: 0.259–0.778, p = 0.004). Major reasons to remove the CVC in the CRBSI-ALT group were local insertion/pocket site infection (23%), persistent symptoms (23%), and infectious' relapses (15%). Conclusions: ALT was shown to be an effective approach to keeping the CVC in place, with no added adverse effects. [ABSTRACT FROM AUTHOR]

Aggressive large B-cell lymphomas (aLBCL) include a heterogeneous group of lymphomas with diverse biological features. One of the approaches to the diagnosis of aLBCL is based on the identification of MYC rearrangements (MYC-R), in addition to BCL2 and BCL6 rearrangements by genetic techniques, mainly fluorescent in situ hybridization (FISH). Because of the low incidence of MYC-R, the identification of useful immunohistochemistry markers to select cases for MYC FISH testing may be useful in daily practice. In a previous work, we identified a strong association between the profile CD10 positive/LMO2 negative expression and the presence of MYC-R in aLBCL and obtained good intralaboratory reproducibility. In this study, we wanted to evaluate external reproducibility. To evaluate whether LMO2 can be a reproducible marker between observers 50 aLBCL cases were circulated among 7 hematopathologists of 5 hospitals. Fleiss' kappa index for LMO2 and MYC were 0.87 and 0.70, respectively, indicating high agreement between observers. In addition, during 2021–2022, the enrolled centers included LMO2 in their diagnostic panels to evaluate prospectively the utility of the marker, and 213 cases were analyzed. Comparing LMO2 with MYC, the group of CD10 positive cases showed higher specificity (86% vs 79%), positive predictive value (66% vs 58%), likelihood positive value (5.47 vs 3.78), and accuracy (83% vs 79%), whereas the negative predictive values remained similar (90% vs 91%). These findings place LMO2 as a useful and reproducible marker to screen MYC-R in aLBCL. [ABSTRACT FROM AUTHOR]

The management of relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) has witnessed dramatic changes in the recent past. Despite the availability of multiple novel immunotherapies in R/R setting, there remains an unmet need for off-the-shelf therapies, particularly in patients with primary refractory, multiply relapsed disease or those experiencing cellular immunotherapy failure. To harness the power of the T-cell mediated immunity, a novel class of drugs called bispecific antibodies (BsAbs) have been developed. These BsAbs are currently under investigation both in frontline and R/R setting and hold the potential to revolutionize the management of LBCL. This review article summarizes the currently available BsAbs, their mode of action, efficacy, and safety data for untreated and R/R LBCL. In addition, the role of these BsAbs in combination with currently available chemoimmunotherapy regimens is also discussed. Two BsAbs have secured FDA approval for R/R LBCL, with expected approval of more BsAbs (including in earlier treatment lines). These drugs provide a highly efficacious and relatively safe treatment option for patients with highly pretreated disease including relapse after cellular immunotherapies. In addition, these BsAbs provide a platform for chemotherapy-free regimen for older/frail patients. [ABSTRACT FROM AUTHOR]

Rosai Dorfman disease (RDD) is a rare non-Langerhans histiocytic disorder, which belongs to the R group of the 2016 revised histiocytic classification. It's characterized by the accumulation of activated histiocytes in the sinusoids of lymph nodes and/or extranodal tissues. Herein, we report a 7-year-old female who was initially suspected to have a lymphoma but was later identified as having RDD. She presented with a history of fever, night sweats, and weight loss, and on physical examination had bilateral cervical lymphadenopathy. Histologic examination of the biopsied cervical lymph nodes showed distended sinuses with S100 and CD68 immunoreactive histiocytes demonstrating emperipolesis, confirming a diagnosis of RDD. The condition is known to be self-limiting. However, evidence from literature and our case management shows that medical therapy can hasten remission in pediatric cases. [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]

The evolutionary conservation of non-core RAG regions suggests significant roles that might involve quantitative or qualitative alterations in RAG activity. Off-target V(D)J recombination contributes to lymphomagenesis and is exacerbated by RAG2' C-terminus absence in Tp53-/- mice thymic lymphomas. However, the genomic stability effects of non-core regions from both Rag1c/c and Rag2c/c in BCR-ABL1+ B-lymphoblastic leukemia (BCR-ABL1+ B-ALL), the characteristics, and mechanisms of non-core regions in suppressing off-target V(D)J recombination remain unclear. Here, we established three mouse models of BCR-ABL1+ B-ALL in mice expressing full-length RAG (Ragf/f), core RAG1 (Rag1c/c), and core RAG2 (Rag2c/c). The Ragc/c (Rag1c/c and Rag2c/c) leukemia cells exhibited greater malignant tumor characteristics compared to Ragf/f cells. Additionally, Ragc/c cells showed higher frequency of off-target V(D)J recombination and oncogenic mutations than Ragf/f. We also revealed decreased RAG cleavage accuracy in Ragc/c cells and a smaller recombinant size in Rag1c/c cells, which could potentially exacerbate off-target V(D)J recombination in Ragc/c cells. In conclusion, these findings indicate that the non-core RAG regions, particularly the non-core region of RAG1, play a significant role in preserving V(D)J recombination precision and genomic stability in BCR-ABL1+ B-ALL. [ABSTRACT FROM AUTHOR]