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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.

Human immunodeficiency virus (HIV) infection is strongly associated with a heightened incidence of lymphomas. To mirror the natural course of human HIV infection, animal models have been developed. These models serve as valuable tools to investigate disease pathobiology, assess antiretroviral and immunomodulatory drugs, explore viral reservoirs, and develop eradication strategies. However, there are currently no validated in vivo models of HIV-associated lymphoma (HAL), hampering progress in this crucial domain, and scant attention has been given to developing animal models dedicated to studying HAL, despite their pivotal role in advancing knowledge. This review provides a comprehensive overview of the existing animal models of HAL, which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection., (© 2024 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

In recent years, the incidence and mortality rates of lymphoma have gradually increased worldwide. Tumorigenesis and drug resistance are closely related to intracellular inflammatory pathways in lymphoma. Therefore, understanding the biological role of inflammatory pathways and their abnormal activation in relation to the development of lymphoma and their selective modulation may open new avenues for targeted therapy of lymphoma. The biological functions of inflammatory pathways are extensive, and they are central hubs for regulating inflammatory responses, immune responses, and the tumour immune microenvironment. However, limited studies have investigated the role of inflammatory pathways in lymphoma development. This review summarizes the relationship between abnormal activation of common inflammatory pathways and lymphoma development to identify precise and efficient targeted therapeutic options for patients with advanced, drug-resistant lymphoma.

Objectives: Patients with myeloproliferative neoplasms (MPNs) are at higher risk of developing secondary malignancies. In this study, we focused on patients with MPNs that complicated lymphoid neoplasms. To analyze the real-world status of lymphoid neoplasm treatment in patients with pre-existing MPNs in Japan, we conducted a multicenter retrospective study., Methods: Questionnaires were sent to collect the data on patients who were first diagnosed with either polycythemia vera, essential thrombocythemia or myelofibrosis and who later were complicated with lymphoid neoplasms defined as malignant lymphoma, multiple myeloma, or chronic lymphocytic leukemia/small cell lymphoma., Results: Twenty-four patients with MPNs complicated by lymphoid neoplasms were enrolled (polycythemia vera, n  = 8; essential thrombocythemia, n  = 14; and primary myelofibrosis, n  = 2). Among these, diffuse large B-cell lymphoma (DLBCL) was the most frequently observed ( n  = 13, 54.1%). Twelve (92.3%) of the patients with DLBCL received conventional chemotherapy. Among these 12 patients, regarding cytoreductive therapy for MPNs, 8 patients stopped treatment, one continued treatment, and two received a reduced dose. Consequently, most patients were able to receive conventional chemotherapy for DLBCL with a slightly higher dose of granulocyte colony-stimulating factor support than usual without worse outcomes. All 3 patients with multiple myeloma received a standard dose of chemotherapy., Conclusion: Our data indicate that if aggressive lymphoid neoplasms develop during the course of treatment in patients with MPNs, it is acceptable to prioritize chemotherapy for lymphoma.

Therapy-related myeloid neoplasms (tMN) are complications of cytotoxic therapies. Risk of tMN is high in recipients of autologous hematopoietic stem cell transplantation (aHSCT). Acquisition of genomic mutations represents a key pathogenic driver but the origins, timing and dynamics, particularly in the context of preexisting or emergent clonal hematopoiesis (CH), have not been sufficiently clarified. We studied a cohort of 1507 patients undergoing aHSCT and a cohort of 263 patients who developed tMN without aHSCT to determine clinico-molecular features unique to post-aHSCT tMN. We show that tMN occurs in up to 2.3% of patients at median of 2.6 years post-AHSCT. Age ≥ 60 years, male sex, radiotherapy, high treatment burden ( ≥ 3 lines of chemotherapy), and graft cellularity increased the risk of tMN. Time to evolution and overall survival were shorter in post-aHSCT tMN vs. other tMN, and the earlier group's mutational pattern was enriched in PPM1D and TP53 lesions. Preexisting CH increased the risk of adverse outcomes including post-aHSCT tMN. Particularly, antecedent lesions affecting PPM1D and TP53 predicted tMN evolution post-transplant. Notably, CH-derived tMN had worse outcomes than non CH-derived tMN. As such, screening for CH before aHSCT may inform individual patients' prognostic outcomes and influence their prospective treatment plans. Presented in part as an oral abstract at the 2022 American Society of Hematology Annual Meeting, New Orleans, LA, 2022., (© 2024. The Author(s).)

We conducted a hospital-based case-control study to explore the association between proximity to various land use types and childhood leukemia and lymphoma. This research involved 428 cases of childhood leukemia and lymphoma (2016-2021), along with a control group of 428 children aged 1-15 in Tehran. We analyzed the risk of childhood cancer associated with land use by employing logistic regression adjusted for confounding factors such as parental smoking and family history. The odds ratio (OR) for children with leukemia and lymphoma residing within 100 m of the nearest highway was 1.87 (95% CI = 1.00-3.49) and 1.71 (95% CI = 1.00-2.93), respectively, in comparison to those living at a distance of 1000 m or more from a highway. The OR for leukemia with exposure to petrol stations within 100 m was 2.15 (95% CI = 1.00-4.63), and for lymphoma it was 1.09 (95% CI = 0.47-2.50). A significant association was observed near power lines (OR = 3.05; 95% CI = 0.97-9.55) within < 100 m for leukemia. However, no significant association was observed between power lines and the incidence of childhood lymphoma. There was no association between bus stations, major road class 2, and the incidence of childhood leukemia and lymphoma. In conclusion, our results suggest a possible association between the incidence of childhood leukemia and proximity to different urban land uses (i.e., highways and petrol stations). This study is the first step in understanding how urban land use affects childhood leukemia and lymphoma in Tehran. However, comprehensive studies considering individual-level data and specific pollutants are essential for a more nuanced understanding of these associations., (© 2024. The Author(s).)

Background: Previous studies have indicated a potential link between the gut microbiota and lymphoma. However, the exact causal interplay between the two remains an area of ambiguity., Methods: We performed a two-sample Mendelian randomization (MR) analysis to elucidate the causal relationship between gut microbiota and five types of lymphoma. The research drew upon microbiome data from a research project of 14,306 participants and lymphoma data encompassing 324,650 cases. Single-nucleotide polymorphisms were meticulously chosen as instrumental variables according to multiple stringent criteria. Five MR methodologies, including the inverse variance weighted approach, were utilized to assess the direct causal impact between the microbial exposures and lymphoma outcomes. Moreover, sensitivity analyses were carried out to robustly scrutinize and validate the potential presence of heterogeneity and pleiotropy, thereby ensuring the reliability and accuracy., Results: We discerned 38 potential causal associations linking genetic predispositions within the gut microbiome to the development of lymphoma. A few of the more significant results are as follows: Genus Coprobacter (OR = 0.619, 95% CI 0.438-0.873, P  = 0.006) demonstrated a potentially protective effect against Hodgkin's lymphoma (HL). Genus Alistipes (OR = 0.473, 95% CI 0.278-0.807, P  = 0.006) was a protective factor for diffuse large B-cell lymphoma. Genus Ruminococcaceae (OR = 0.541, 95% CI 0.341-0.857, P  = 0.009) exhibited suggestive protective effects against follicular lymphoma. Genus LachnospiraceaeUCG001 (OR = 0.354, 95% CI 0.198-0.631, P  = 0.0004) showed protective properties against T/NK cell lymphoma. The Q test indicated an absence of heterogeneity, and the MR-Egger test did not show significant horizontal polytropy. Furthermore, the leave-one-out analysis failed to identify any SNP that exerted a substantial influence on the overall results., Conclusion: Our study elucidates a definitive causal link between gut microbiota and lymphoma development, pinpointing specific microbial taxa with potential causative roles in lymphomagenesis, as well as identifying probiotic candidates that may impact disease progression, which provide new ideas for possible therapeutic approaches to lymphoma and clues to the pathogenesis of lymphoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Han, Fu, Chai, Guo, Du, Li and Wang.)

Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. In addition, there may be a link between the use of thiopurines or anti-tumor necrosis factor drugs (anti-TNF) and these pathologies. The treatment of patients with Crohn's disease who have previously been diagnosed with lymphoma is a challenge for gastroenterologists. In this report, we examine important clinical issues related to the treatment of patients with inflammatory bowel disease with active lymphoma, as well as of patients with hematological cancer history. In this discussion, we take into account most of the available treatments for inflammatory bowel disease, as well as the impact of chronic inflammation and viral infections. In addition, we try to find common ground for the development of lymphoproliferative disorders and autoimmune diseases. Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. Chronic inflammatory processes and viral infections play an important role in carcinogenesis. In addition, there may be a link between the use of thiopurines or anti-TNF drugs and these pathologies. A significant risk of the development of lymphoma in people undergoing each therapy should be considered, and it should be estimated how much greater this risk will be in patients with a history of lymphoproliferative disorders. The following review is an attempt to answer which therapy would be the most appropriate for patients with Crohn's disease and a history of lymphoma treatment. A lack of clear guidelines creates great challenges for doctors.

Introduction: Since malignancy during pregnancy is uncommon, information regarding contraception selection or sterilization at delivery is limited. The objective of this study was to examine the type of long-acting reversible contraception or surgical sterilization procedure chosen by pregnant patients with malignancy at delivery., Material and Methods: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample in the USA. The study population was vaginal and cesarean deliveries in a hospital setting from January 2017 to December 2020. Pregnant patients with breast cancer (n = 1605), leukemia (n = 1190), lymphoma (n = 1120), thyroid cancer (n = 715), cervical cancer (n = 425) and melanoma (n = 400) were compared with 14 265 319 pregnant patients without malignancy. The main outcome measures were utilization of long-acting reversible contraception (subdermal implant or intrauterine device) and performance of permanent surgical sterilization (bilateral tubal ligation or bilateral salpingectomy) during the index hospital admission for delivery, assessed with a multinomial regression model controlling for clinical, pregnancy and delivery characteristics., Results: When compared with pregnant patients without malignancy, pregnant patients with breast cancer were more likely to proceed with bilateral salpingectomy (adjusted odds ratio [aOR] 2.30) or intrauterine device (aOR 1.91); none received the subdermal implant. Pregnant patients with leukemia were more likely to choose a subdermal implant (aOR 2.22), whereas those with lymphoma were more likely to proceed with bilateral salpingectomy (aOR 1.93) and bilateral tubal ligation (aOR 1.76). Pregnant patients with thyroid cancer were more likely to proceed with bilateral tubal ligation (aOR 2.21) and none received the subdermal implant. No patients in the cervical cancer group selected long-acting reversible contraception, and they were more likely to proceed with bilateral salpingectomy (aOR 2.08). None in the melanoma group chose long-acting reversible contraception. Among pregnant patients aged <30, the odds of proceeding with bilateral salpingectomy were increased in patients with breast cancer (aOR 3.01), cervical cancer (aOR 2.26) or lymphoma (aOR 2.08). The odds of proceeding with bilateral tubal ligation in pregnant patients aged <30 with melanoma (aOR 5.36) was also increased., Conclusions: The results of this nationwide assessment in the United States suggest that among pregnant patients with malignancy, the preferred contraceptive option or method of sterilization at time of hospital delivery differs by malignancy type., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: We described the real-life epidemiology and causes of infections on the different therapy phases in patients undergoing chimeric antigen receptor (CAR) T-cells directed towards CD19+ or BCMA+ cells., Methods: All consecutive patients receiving CAR T-cell therapy at our institution were prospectively followed-up. We performed various comparative analyses of all patients and subgroups with and without infections., Results: Ninety-one adults mainly received CAR T-cell therapy for acute leukaemia (53%) and lymphoma (33%). We documented a total of 77 infections in 47 (52%) patients, 37 (48%) during the initial neutropenic phase and 40 (52%) during the non-neutropenic phase. Infections during the neutropenic phase were mainly due to bacterial (29, 78%): catheter infections (11 [38%] cases), endogenous source (5 [17%]), and Clostridioides difficile (5 [17%]). Patients receiving corticosteroids after CAR T-cell therapy had a higher risk of endogenous infection (100% vs. 16%; p = .006). During the non-neutropenic phase, bacterial infections remained very frequent (24, 60%), mainly with catheter source (8, 33%). Respiratory tract infections were common (17, 43%)., Conclusions: Infections after CAR T-cell therapy were frequent. During the neutropenic phase, it is essential to prevent nosocomial infections and balance the use of antibiotics to lower endogenous bacteraemia and Clostridial infection rates., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The hematologic system is frequently involved in sarcoidosis. Lymphopenia is the most common hematologic manifestation noted, although anemia and thrombocytopenia also occur. The etiology of these common manifestations can be direct granulomatous infiltration of bone marrow, lymph nodes, or spleen or related to immunologic dysfunction. Although not life threatening, these problems can lead to cytopenias requiring close monitoring in patients receiving a variety of disease treatments. The relationship between sarcoidosis and malignancy remains complex. However, some sarcoidosis patients are at increased risk for the development of malignancies, particularly lymphomas and gastrointestinal cancers. Conversely, cancer patients can experience an increase in the likelihood for the development of breast cancer and lymphomas., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Therapy-related myeloid neoplasms (t-MN), either myelodysplastic neoplasms (t-MDS) or acute myeloid leukemias (t-AML), have a poor prognosis and allogeneic haematopoietic cell transplantation (allo-HCT) represents the only curative option. In this multicenter, registry-based study, we analyzed outcomes of 378 patients undergoing first allo-HCT between 2006-2017 for t-MN arising secondary to lymphoma treatment. Median age was 58 years at allo-HCT; 222 (59%) had a diagnosis of t-MDS and 156 (41%) of t-AML, respectively. At the time of allo-HCT, 46% of t-MN cases were reported as in complete remission (CR) and 15% of lymphomas were recorded as not in remission. A reduced intensity conditioning regimen was used in 70% of cases. For the entire cohort, 5-year OS, and t-MN PFS, relapse incidence and NRM were 32%, 28%, 35% and 37%, respectively. In multivariable analysis, undergoing allo-HCT with t-MN not in CR and older age were associated with significantly worse OS, PFS and NRM. At 5 years post allo-HCT, the relapse incidence of lymphoma was low at 3%, while the rate of secondary malignancies was 8%. This analysis shows the curative potential of allo-HCT for patients with t-MN arising secondary to lymphoma treatment in approximately a third of patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The development of lymphoma is a complex multistep process that integrates numerous experimental findings and clinical data that have not yet yielded a definitive explanation. Studies of oncogenic viruses can help to deepen insight into the pathogenesis of lymphoma, and identifying associations between lymphoma and viruses that are established and unidentified should lead to cellular and pharmacologically targeted antiviral strategies for treating malignant lymphoma. This review focuses on the pathogenesis of lymphomas associated with hepatitis B and C, Epstein-Barr, and human immunodeficiency viruses as well as Kaposi sarcoma-associated herpesvirus to clarify the current status of basic information and recent advances in the development of virus-associated lymphomas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Guo, Zhan and Bai.)

Chimeric antigen receptor (CAR)-T-cell therapy has greatly improved outcomes for patients with relapsed or refractory hematological malignancies. However, challenges such as treatment resistance, relapse, and severe toxicity still hinder its widespread clinical application. Traditional transcriptome analysis has provided limited insights into the complex transcriptional landscape of both leukemia cells and engineered CAR-T-cells, as well as their interactions within the tumor microenvironment. However, with the advent of single-cell sequencing techniques, a paradigm shift has occurred, providing robust tools to unravel the complexities of these factors. These techniques enable an unbiased analysis of cellular heterogeneity and molecular patterns. These insights are invaluable for precise receptor design, guiding gene-based T-cell modification, and optimizing manufacturing conditions. Consequently, this review utilizes modern single-cell sequencing techniques to clarify the transcriptional intricacies of leukemia cells and CAR-Ts. The aim of this manuscript is to discuss the potential mechanisms that contribute to the clinical failures of CAR-T immunotherapy. We examine the biological characteristics of CAR-Ts, the mechanisms that govern clinical responses, and the intricacies of adverse events. By exploring these aspects, we hope to gain a deeper understanding of CAR-T therapy, which will ultimately lead to improved clinical outcomes and broader therapeutic applications.

Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the mechanisms interconnecting inflammation and tumorigenesis has led to the study of the NLRP3 inflammasome in the setting of various neoplasms. Despite a plethora of data regarding solid tumors, NLRP3 inflammasome's implication in the pathogenesis of hematological malignancies only recently gained attention. In this review, we investigate its role in normal lymphopoiesis and lymphomagenesis. Considering that lymphomas comprise a heterogeneous group of hematologic neoplasms, both tumor-promoting and tumor-suppressing properties were attributed to the NLRP3 inflammasome, affecting neoplastic cells and immune cells in the tumor microenvironment. NLRP3 inflammasome-related proteins were associated with disease characteristics, response to treatment, and prognosis. Few studies assess the efficacy of NLRP3 inflammasome therapeutic targeting with encouraging results, though most are still at the preclinical level. Further understanding of the mechanisms regulating NLRP3 inflammasome activation during lymphoma development and progression can contribute to the investigation of novel treatment approaches to cover unmet needs in lymphoma therapeutics.

Purpose: Post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic stem transplantation (HCT) or solid organ transplantation (SOT) result in poorer outcomes, including death. There are limited large cohort data on the incidence and natural course of PTLD in Asians., Materials and Methods: We investigated PTLD using Korean national health insurance claims data of 47,518 patients who underwent HCT or SOT in 2008-2020. Patient demographics, time and type of PTLD diagnosis, type of PTLD treatment, and death data were collected. We used Fine and Gray subdistribution hazard models to calculate the cumulative incidence and risk factors for PTLD., Results: During median follow-up of 5.32 years, PTLD occurred in 294 of 36,945 SOT patients (0.79%) and 235 of 10,573 HCT patients (2.22%). Cumulative incidence of PTLD were 0.49% at 1 year, 1.02% at 5 years, and 1.50% at 10 years post-transplantation. Age < 20 years (subdistribution hazard ratio [SHR] of 1.67 in age 10-19, SHR 1.51 in age 0-9), HCT (SHR 3.02), heart transplantation (SHR 2.27), and liver transplantation (SHR 1.47) were significant risk factors for PTLD. The presence of PTLD was associated with an increased risk of death (hazard ratio of 2.84). Overall, 5-year survival of PTLD patients was 68.9% (95% confidence interval, 64.9 to 73.2)., Conclusion: We observed a steady increase in PTLD over 10 years after HCT or SOT in this large cohort study. Pediatric age group, HCT, liver transplantation, and heart transplantation were suggested to be risk factors for PTLD, and PTLD was associated with a higher risk of death.

Purpose: The effect of chronic low dose-rate radiation exposure on cancers was investigated by analyzing the data of mice experiments conducted at the Institute for Environmental Sciences (IES). This analysis focuses on the differences between malignant lymphomas and solid cancers., Materials and Methods: The analysis is conducted based on the mathematical model introduced in our previous work. The model is expanded to analyze malignant lymphomas and solid cancers separately. Using the expanded model, the effect of chronic low dose-rate radiation on malignant lymphomas and solid cancers are discussed based on their occurrences, progressions, and mortalities., Results: Non-irradiated control group and 20 mGy/day × 400 days irradiated groups are analyzed. The analysis showed that radiation exposure shortened mean life expectancy for both malignant lymphomas and solid cancers (shorter by 89.6 days for malignant lymphomas and 149.3 days for solid cancers). For malignant lymphomas, both the occurrence and the progression are affected by radiation exposure. The mean age at which malignant lymphoma developed in mice was shortened by 32.7 days and the mean progression period was shortened by 57.3 days. The occurrence of solid cancer is also affected by radiation exposure, wherein the mean age at which solid cancer develops was shortened by 147.9 days. However, no significant change in progression period of solid cancers was seen in the analysis., Conclusions: The analysis showed that the occurrence and mean lifespan are affected in both malignant lymphomas and solid cancers. The shortening of the progression period is only seen in malignant lymphoma, no significant change was observed in solid cancers.

Purpose of Review: Epstein-Barr Virus (EBV) is a ubiquitous herpesvirus that affects almost all humans and establishes lifelong infections by infecting B-lymphocytes leading to their immortalization. EBV has a discrete life cycle with latency and lytic reactivation phases. EBV can reactivate and cause lymphoproliferation in both immunocompetent and immunocompromised individuals. There is sparse literature on monitoring protocols for EBV reactivation and no standardized treatment protocols to treat EBV-driven lymphoproliferation., Recent Findings: While there are no FDA-approved therapies to treat EBV, there are several strategies to inhibit EBV replication. These include immunosuppression reduction, nucleoside analogs, HDAC inhibitors, EBV-specific cytotoxic T-lymphocytes (CTLs), and monoclonal antibodies, such as rituximab. There is currently an open clinic trial combining the use of a HDAC inhibitor, nanatinostat, and ganciclovir to treat refractory/relapsed EBV lymphomas. Another novel therapy includes tabelecleucel, which is an allogenic EBV-directed T-cell immunotherapy that was approved by the European Medicines Agency, but is currently only available in the US for limited use in relapsed or refractory EBV-positive PTLD. Further research is needed to establish EBV monitoring protocols in high-risk populations, such as those with autoimmune disease, cancer, HIV, or receiving immunosuppressive therapy. Additionally, standardized treatments for both the prevention of EBV reactivation in high-risk populations and treatment of EBV reactivation and lymphoproliferation need to be established., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Physical activity is known to convey protection against several cancers. However, results on the risk of lymphoma overall and its subtypes have been inconsistent. The aim of this study was to investigate occupational and recreational physical activity in relation to risk of lymphoma subtypes adjusting for established occupational risk factors. We applied standardized tools to assess energy expenditure at work and in recreational physical activities to the questionnaire information on lifetime work and exercise history in 1117 lymphoma cases, including Hodgkin lymphoma, and B-cell (including chronic lymphocytic leukemia, and multiple myeloma) and T-cell non-Hodgkin's lymphoma (NHL) subtypes, and 1207 controls who took part in the multicentre European EpiLymph case-control study. We calculated the risk of lymphoma (all subtypes), B-cell NHL and its most represented subtypes, and Hodgkin's lymphoma (all subtypes) associated with weekly average Metabolic Equivalent of Task (MET-hours/week) and cumulative MET-hours of lifetime recreational, occupational, and total physical activity, with unconditional logistic regression and polytomous regression analysis adjusting by age, centre, sex, education, body mass index, history of farm work and solvent use. We observed an inverse association of occupational, and total physical activity with risk of lymphoma (all subtypes), and B-cell non-Hodgkin's lymphoma among women, and an upward trend in risk of Hodgkin's lymphoma with recreational and total physical activity among men, for which we cannot exclude chance or bias. Our results suggest no effect of overall physical activity on risk of lymphoma and its subtypes., Competing Interests: Declaration of Competing Interest Mariagrazia Zucca reports was provided by EpiLymph paper on physical activity. Mariagrazia Zucca reports a relationship with EpiLymph paper on physical activity that includes: board membership. Mariagrazia Zucca has patent pending to Mariagrazia Zucca. Pierluigi Cocco reports financial support was provided by Italian Association for Cancer Research. Pierluigi Cocco reports a relationship with Italian Ministry for Education, University and Research that includes: funding grants. Marc Maynadie reports a relationship with Janssen Pharmaceuticals Inc that includes: funding grants. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lymphoma is a heterogeneous group of malignancies arising from lymphocytes, which poses a significant challenge in terms of diagnosis and treatment due to its diverse subtypes and underlying mechanisms. This review aims to explore the shared and distinct features of various forms of lymphoma predisposing conditions, with a focus on genetic, immunological and molecular aspects. While diseases such as autoimmune disorders, inborn errors of immunity and iatrogenic immunodeficiencies are biologically and immunologically distinct, each of these diseases results in profound immune dysregulation and a predisposition to lymphoma development. Interestingly, the increased risk is often skewed towards a particular subtype of lymphoma. Patients with inborn errors of immunity in particular present with extreme forms of lymphoma predisposition, providing a unique opportunity to study the underlying mechanisms. External factors such as chronic infections and environmental exposures further modulate the risk of lymphoma development. Common features of conditions predisposing to lymphoma include: persistent inflammation, recurrent DNA damage or malfunctioning DNA repair, impaired tumor surveillance and viral clearance, and dysregulation of fundamental cellular processes such as activation, proliferation and apoptosis. Our growing understanding of the underlying mechanisms of lymphomagenesis provides opportunities for early detection, prevention and tailored treatment of lymphoma development., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Chimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy., Method: We searched PubMed, the Cochrane Library, Embase and Web of Science from January 2012 to August 2022 to find data reporting the results of CAR-T cells therapy combined with PD-1 in tumor patients. An updated search was conducted in October 2023. The partial response rate (PR), complete response rate (CR), objective response rate (ORR), mortality rate, and incidence of adverse reactions were calculated., Results: We analyzed 57 lymphoma patients from 5 clinical trials. The pooled partial, complete and overall response rates were 21% (95% CI 0.06-0.39, I 2  = 0.37%), 27% (95% CI 0.03-0.60, I 2  = 60.43%) and 65% (95% CI 0.23-0.98, I 2  = 76.31%), respectively. The pooled incidence of cytokine release syndrome, neutropenia, fever, and fatigue was estimated to be 57% (95% CI 0.08-0.99, I 2  = 85.20%), 47% (95% CI 0.14-0.81, I 2  = 74.17%), 59% (95% CI 0.27-0.89, I 2  = 60.23%), and 50% (95% CI 0.13-0.87, I 2  = 73.89%), respectively., Conclusion: CAR-T-cell therapy combined with anti-PD-1 immunotherapy in the treatment of lymphoma patients has efficacy, and the most common adverse effect is fever., Registration: The protocol was registered in prospero, with the registration number CRD42022342647., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ≥3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of pediatric heart transplant (PHTx). 18F-FDG PET/CT has been used to differentiate early lympho-proliferation from more advanced PTLD. We report our experience with PET/CT in the management of PTLD following PHTx., Methods: This was a retrospective study of 100 consecutive PHTx recipients at our institution between 2004 and 2018. Patients who underwent PET/CT or conventional CT scans to evaluate for PTLD or high Epstein-Barr viral load were included., Results: Males, eight females. Median age at transplant was 3.5 months (IQR = 1.5-27.5). Median age at PTLD diagnosis was 13.3 years (IQR = 9.2-16.1). Median time between transplant and PTLD diagnosis was 9.5 (IQR = 4.5-15) years. Induction agents were used in 12 patients (50%): Thymoglobulin (N = 9), anti-IL2 (N = 2), and Rituximab (N = 1). Eighteen patients (75%) had PET/CT, of whom 14 had 18FDG-avid PTLD. Six had conventional CT. Nineteen patients (79.2%) had diagnostic biopsy confirmation of PTLD, and 5 (20.8%) had excisional biopsies. Two patients had Hodgkin's lymphoma; nine had monomorphic PTLD; eight had polymorphic PTLD; five were classified as other. Nine patients had monomorphic PTLD, including seven with diffuse large cell lymphoma (DLBC) and one with T cell lymphoma. The majority (16/24) had multi-site involvement at PTLD diagnosis, and PET/CT showed that 31.3% (5/16) had easily accessible subcutaneous nodes. Seventeen patients (overall survival 71%) underwent successful treatment without recurrence of PTLD. Of seven deaths (7/24, 29%), five had DLBC lymphoma, one had polymorphic PTLD and one had T-cell lymphoma., Conclusion: PET-CT allowed simultaneous anatomical and functional assessment of PTLD lesions, while guiding biopsy. In patients with multiple lesions, PET/CT revealed the most prominent and active lesions, improving diagnostic accuracy., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objectives: Autologous stem cell transplant (ASCT) is a widely used therapy for lymphoma patients and can nowadays be performed on an outpatient basis. This study aimed to describe transfusion support in lymphoma patients undergoing ASCT and identify increased or prolonged transfusion requirement predictors., Materials and Methods: A retrospective study of all consecutive lymphoma patients undergoing ASCT between 2010 and 2020., Results: Out of 226 patients, 145 (64%) received red blood cell (RBC) transfusions, whereas all 226 (100%) required platelet transfusion (PT). Transfusions between Day +1 and +30 were higher in patients over 60 (2 [1-4] vs. 2 [0-2] RBC; p = 0.001 and 4 [2-8] vs. 3 [2-4] PT; p < 0.001); patients with pre-transplant anaemia (4 [2.5-6] vs. 2 [0-2] RBC; p < 0.001 and 5 [3-9] vs. 3 [2-4] PT; p = 0.001); pre-transplant thrombocytopenia (2 [1-4] vs. 2 [0-2] RBC; p < 0.001 and 4 [3-8.5] vs. 2 [1-3] PT; p < 0.001) or CD34 + cell dose <4 × 10 6 /kg (2 [0-4] vs. 2 [0-2] RBC; p = 0.024 and 4 [2-6] vs. 2 [1-3.5] PT; p < 0.001). RBC transfusion independence was reached later in patients receiving carmustine, cytarabine, etoposide and melphalan (BEAM) (hazard ratio [HR] 1.6; confidence interval [CI] 1.1-2.3) and those requiring RBC before infusion and/or with pre-transplant anaemia (HR 2.2; CI 1.4-3.4). Age above 60 (HR 1.4; CI 1.0-1.9), BEAM conditioning (HR 1.4; CI 1.0-2.0) and pre-transplant thrombocytopenia and/or requiring PT before infusion (HR 1.8; CI 1.4-2.5) entailed longer time until PT independence., Conclusion: These four factors (age ≥60 years; BEAM conditioning, CD34 + dose <4 × 10 6 /kg and pre-transplant cytopenia and/or Day -10 to 0 transfusion) allowed dividing patients into three groups with significant differences between them regarding the time until transfusion independence., (© 2023 International Society of Blood Transfusion.)

T cells engineered to express chimeric antigen receptors (CARs) targeting CD19 have demonstrated impressive activity against relapsed or refractory B-cell cancers yet fail to induce durable remissions for nearly half of all patients treated. Enhancing the efficacy of this therapy requires detailed understanding of the molecular circuitry that restrains CAR-driven antitumor T-cell function. We developed and validated an in vitro model that drives T-cell dysfunction through chronic CAR activation and interrogated how CAR costimulatory domains, central components of CAR structure and function, contribute to T-cell failure. We found that chronic activation of CD28-based CARs results in activation of classical T-cell exhaustion programs and development of dysfunctional cells that bear the hallmarks of exhaustion. In contrast, 41BB-based CARs activate a divergent molecular program and direct differentiation of T cells into a novel cell state. Interrogation using CAR T cells from a patient with progressive lymphoma confirmed the activation of this novel program in a failing clinical product. Furthermore, we demonstrate that 41BB-dependent activation of the transcription factor FOXO3 is directly responsible for impairing CAR T-cell function. These findings identify that costimulatory domains are critical regulators of CAR-driven T-cell failure and that targeted interventions are required to overcome costimulation-dependent dysfunctional programs., (© 2023 by The American Society of Hematology.)

The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. Among 309 CNSL patients aged ≥60, 11.7% had EBV + tumors of which 72.2% were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD). Younger age, SOT or autoimmune disease, and immunosuppressive treatment correlated highly with EBV-positivity. EBV + tumors were associated with absent C-MYC and BCL6 expression. EBV + PTLD was more likely to be associated with the absence of CD5 expression. EBV + non-PTLD had better median OS (not reached) compared to EBV + PTLD (10.8 months) and EBV-negative patients (43 months). Multivariable Cox regression analysis showed that age, performance status, and PTLD were negative predictors of OS. EBV status and immunosuppressive treatment were not correlated with OS. Our findings merit further investigation of EBV + PCNSL tumors and EBV-directed therapies.

Clinical data on primary central nervous system (CNS) lymphoma (PCNSL) patients is mostly generated from prospective studies, and many frail real-world patients are not included. Recently,the diagnosis and treatment of PCNSL patients was confounded by the COVID-19 pandemic. In particular, treatment with high-dose cytarabine was linked to increased risk of pneumonia and virus persistence. We report on outcome of the induction regimen R-MIV (rituximab, methotrexate, ifosfamide, and vincristine) involving intensive administration of high-dose methotrexate (3.5 g/m 2 ) with ifosfamide, every 2 weeks and rituximab once per week for six doses. The median age and performance status (PS) for 64 patients was 58 years and 2 (PS 3; 22%) respectively. The overall response rate by magnetic resonance imaging/computed tomography (MRI/CT) was 73% (n = 46/63), with an additional 17.5% (n = 11/63) patients without measurable disease at baseline. Grade 3-4 haematological toxicity was low for R-MIV (neutropenia: 25% and thrombocytopenia: 1%). Three patients (4.7%) died from treatment-related toxicity. Co-existence of SARS-CoV-2 infection with cytomegalovirus reactivation and the varicella-zoster virus in two patients was fatal. Fifty patients (78%) were eligible for consolidation. Median progression-free and overall survival were not reached (median follow-up: 44 months). In conclusion, the R-MIV regimen is feasible in routine practice, effective and safe, even during the COVID-19 pandemic., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The Coronavirus disease 2019 (COVID-19) pandemic has dramatically impacted the health risk and management of patients with lymphoma. Clinical evaluations on the impact of COVID-19 on lymphoma patients are currently limited however, reports have shown a correlation with specific variants and more severe COVID-19 complications and higher mortality rates relative to other disease states and age-matched populations. During peak pandemic periods this created a concerning management problem for clinicians and raised the question of how different immunocompromised states increase COVID-19-associated risk and provided insights into how immunity interacts with the circulating variant, including the effects of low virulent variants in vaccinated lymphoma populations. Treatment management approaches, polymerase chain reaction tests and rapid antigen screening guidelines have been offered in an attempt to reduce the risk of harm to lymphoma patients, particularly prior to and following bone marrow or stem cell transplant. Here we systematically review the current literature to provide a novel global perspective on incidence, mortality, management and rapid antigen test (RAT) screening for COVID-19, in patients with various subtypes of lymphoma. Furthermore, lessons learned from emerging variants that continue to inform evolving lymphoma management and public health policies are addressed across these associated matters., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Several guidelines classify autologous stem cell transplantation (ASCT) as a low to intermediate risk group for infection. In a nationwide population-based study, using the Korean Health Insurance Review and Assessment Service database, patients with lymphoma and multiple myeloma (MM) who underwent ASCT from 2002 to 2016 were retrospectively analyzed. Cumulative incidence rates (CIRs) and risk factors of opportunistic infections were investigated. CIRs of fungal, Varicella zoster virus (VZV), cytomegalovirus (CMV), and Pneumocystis jirovecii infections in lymphoma were 7.9%, 16.0%, 7.4%, and 5.1%, respectively, and CIRs in MM were 6.3%, 19.1%, 4.2%, and 5.6%, respectively. Fungal infection was significantly higher in patients with previous infection (Hazard ratio (HR) 2.003, p = 0.005) in lymphoma. Incidence of CMV infection was significantly higher in patients with prior CMV infection: HR 4.920, p < 0.001 (lymphoma); HR 3.022, p = 0.030 (MM). VZV infection was significantly lower in patients receiving prophylaxis: HR 0.082, p < 0.001 (lymphoma); HR 0.096, p < 0.001 (MM). For P. jirovecii infection, busulfex and melphalan conditioning (HR 1.875, p = 0.032) and previous P. jirovecii infection (HR 4.810, p < 0.001) had a higher incidence in MM. Patients who underwent ASCT should receive VZV prophylaxis and prophylaxis for fungal and P. jirovecii may be considered in patients with previous same infection., (© 2023. The Author(s).)

Primary CNS Lymphoma (PCNSL) is a rare form aggressive extra nodal     non-Hodgkin Lymphoma (NHL) that comprising 1-2% of the primary brain tumors that develops in the brain, spinal cord, eye or leptomeningeal area without evidence of systemic involvement. The overall incidence of PCNSL with immunocompetent patients is only 0,47/100.000 year in PCNSL. Approximately 10-20% of patients have ocular involvement and around one third have multifocal neurological disease. Overall long-term survival rate only 20-40%, this is because the management of PCNSL is limited to ability of the drug due to cross the blood brain barrier (BBB). We present a B-cell central nervous system lymphoma in an immunocompetent patient who treat responses with chemotherapy.          A 35-year-old man presented to our hospital with suddenly unconscious 4 hours before admission. He was experiencing headache and blurred of vision withing 3 months and have episode seizure. On Examination, GCS E2 M3 Aphasia, Hemiparesis dextra, papil edema, VOD/VOS: NLP. The other physical exam was normal. Laboratory tests  Hb 10,7 g/dl, LDH 446 U/L, and D-dimer 3,21ug/ml.  Rubella IgG 76,9, CMV Ig G 245,6 and, HSV IgG and IgM negative, HIV test non-reactive, Toxoplasma IgG and Toxoplasma IgM negative, HbsAg and HCV test negative. Brain MRI and MRI Spectroscopy: Lobulated mass size 7,08 cm x 4,75 cm at caudates nucleus sinistra-periventricular lateralis sinistra, Cholin/NAA ratio: 5-9, Cholin/Creatin ration 6-11 suspect malignancy dd/Lymphoma. MRI whole spine: Bulging discus intervertebral C4-C5. Chest and Abdomen CT-Scan are normal. Bone Survey normal, EEG: Epileproform left temporal. Cerebrospinal Fluid: Gliosis reaction sup malignancy.The patient underwent craniotomy and biopsy Pathology Anatomy and IHC Basal Ganglia revealed a Diffuse Large B Cell Lymphoma (NHL) Non-Germinal Center, CD 20 +, Ki 67 95% (High Grade), CD 45 +, CD 3 -, BCL6 +, Mum 1+. The patient we give induction therapy with RMP Regimens (Rituximab 375 mg/m2, day 1, 15 and 29, High Dose Methotrexate (HDMTX) 3000mg/m2 day 2, 16 and 30, and Procarbazine 60mg/m2 day 3-12) because Procarbazine in not available in Palembang we change to Dacarbazine 375mg/m2 days 3,17 and 31), Dexamethasone 5mg/6 hours, and has finished  Low Dose Whole Brain Radiotherapy for consolation therapy. PCNSL is rare form aggressive extra nodal NHL, especially in Immunocompetent patient. In this particular case of patients High Dose Methotrexate Chemotherapy has achieved high respond especially for this patient that showed GCS E4M5V6 and recovery neurological deficit after 2 cycle chemotherapy.

Although >10% of primary CNS lymphoma (PCNSL) patients are ≥80 years, data on this population are limited. We analyzed 19 consecutive octogenarians with PCNSL treated with high-dose methotrexate (HD-MTX)-based chemotherapy at our institution concerning outcome, prognostic factors and living conditions at six-month follow-up for 11 patients alive and in remission. Seven patients received intracerebroventricular (ICV) treatment additional to systemic therapy. Median follow-up was 27.3 months. Median overall survival was 16.3 months. Positive prognosticators of survival were application of ICV treatment ( p  = 0.033) and female gender ( p  = 0.015). All 11 patients alive and in remission at 6-month follow-up were living at home with a median Karnofsky performance score of 60 (range 50-90) and a median instrumental activities of daily living score of 3 (range 1-8). HD-MTX-based polychemotherapy including ICV treatment was feasible in this population, patients in remission needed moderate support in everyday live.

Clonal hematopoiesis (CH) refers to the disproportionate expansion of hematopoietic stem cell clones and their corresponding progeny following the acquisition of somatic mutations. CH is common at the time of diagnosis in patients with blood cancers, including multiple myeloma (MM) and lymphoma. The presence of CH mutations correlates with IL-6 mediated inflammation and may result in lymphoma or MM modulation through microenvironment effects or by manifestations of the mutations themselves within the founding tumor clone. As might be expected with a variety of mutations and multiple potential mechanisms, CH exerts context-dependent effects, being protective in some settings and harmful in others. Though CH is very common in patients with hematologic malignancies, how it intersects with therapy and the natural disease course of these cancers are active areas of investigation. In lymphomas and MM specifically, patients have high rates of CH at diagnosis and are subsequently exposed to therapies, such as cytotoxic chemotherapy, that can cause CH progression to overt hematologic malignancy. The expanding diversity of treatment modalities for these cancers also increases the opportunities for CH to impact clinical outcome and modulate clinical responses. Here we review the basic biology and known health effects of CH, and we focus on the clinical relevance of CH in lymphoma and MM., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease standing in the crossroads of autoimmunity and lymphomagenesis, characterized by chronic B-cell hyperactivity and ectopic lymphoid tissue neoformation, potentially driving lymphoid malignant transformation. Lymphoma development is considered the most serious complication of pSS., Areas Covered: 'Old-classical' biomarkers (clinical, serological, hematological, and histological) validated in the past are analyzed under the perspective of recently published research. Biomarkers that have emerged during the last decade are subdivided to 'old-new' and 'newly proposed-novel' ones, including biomarkers pathophysiologically related to B-cell differentiation, lymphoid organization, and immune responses, identified in serum and tissue, both at genetic and protein level. Upcoming new imaging biomarkers, promising for further patient stratification, are also analyzed., Expert Opinion: Salivary gland enlargement and cryoglobulinemia still remain the best validated 'classical-old' biomarkers for lymphoma development. Though new biomarkers still need to be validated, some can be used for the identification of high-risk patients long before lymphoma diagnosis, and some might be more relevant in distinct age subgroups, while others have an added value in the assessment of lymphoma remission or relapse. Future development of composite indices, integrating old and recently proposed biomarkers, could contribute to a more precise lymphoma prediction model.

Background: Patients with relapsed or refractory (R/R) lymphomas have benefited from chimeric antigen receptor (CAR)-T-cell therapy. However, this treatment is linked to a high frequency of adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity. There has been increasing interest in hematological toxicity in recent years, as it can result in additional complications, such as infection or hemorrhage, which remain intractable., Methods: We conducted a retrospective, single-institution study to evaluate the patterns and outcomes of cytopenia following CAR-T-cell infusion and potential associated factors., Results: Overall, 133 patients with R/R lymphoma who received CAR-T-cell therapy from June, 2017 to April, 2022 were included in this analysis. Severe neutropenia, anemia and thrombocytopenia occurred frequently (71, 30 and 41%, respectively) after CAR-T-cell infusion. A total of 98% of severe neutropenia and all severe thrombocytopenia cases occurred in the early phase. Early severe cytopenia was associated with CRS incidence and severity, as well as peak inflammatory factor (IL-6, C-reactive protein (CRP), and ferritin) levels. In multivariate analysis, prior hematopoietic stem cell transplantation (HSCT), baseline hemoglobin (HB), and lymphodepleting chemotherapy were independent adverse factors associated with early severe cytopenia. In addition, 18% and 35% of patients had late neutrophil- and platelet (PLT)-related toxicity, respectively. In multivariate analysis, lower baseline PLT count was an independent factor associated with late thrombocytopenia. More severe cytopenia was associated with higher infection rates and poorer survival., Conclusions: This research indicates that improved selection of patients and management of CRS may help to decrease the severity of cytopenias and associated AEs and improve survival following CAR-T-cell therapy., Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT03196830, identifier NCT03196830., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Zhang, Shan, Zong, Geng, Li, Chen, Yu, Xu, Li and Wu.)

Inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. Individuals with IBD are at increased risk for several malignancies originating in the intestine, such as colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, and anal cancer. There are also several extraintestinal malignancies associated with IBD and IBD therapies, including cholangiocarcinoma, skin cancer, hematologic malignancies, genitourinary cancer, cervical cancer, and prostate cancer. The authors summarize the risk of cancer in patients with IBD, diagnosis and management of colorectal neoplasia in IBD, and management of patients with IBD and active or recent cancer., Competing Interests: Disclosure J.E. Axelrad reports receiving research grants from BioFire Diagnostics; consultancy fees or honorarium from BioFire Diagnostics, Janssen, Pfizer, Abbvie, and BMS; and holds US Patent 2012/0052124A1 and no other conflicts of interest. A.K. Holmer reports consultancy fees or honorarium from Pfizer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Night shift work can disrupt circadian rhythm and cause chronic sleep deprivation, which might increase the risk of lymphoma through immunosuppression and oxidative stress., Material and Methods: We investigated the association between night shift work and risk of lymphoma subtypes in 867 incident cases and 774 controls, who participated in a multicentre Italian study between 2011 and 2017. Based on questionnaire information, occupational experts assessed the lifetime probability of night shift work, the total number of night shifts and years of night shift work among study participants. OR and 95% CI for lymphoma and its major subtypes associated with night shift work was calculated with logistic regression, adjusting by age, gender, education, study area, marital status and family history of haemolymphatic cancer., Results: Ever working night shifts was associated with an increase in the risk of chronic lymphocytic leukaemia (CLL) (OR 1.9, 95% CI 1.14 to 3.32), which was highest after a 15-34 years latency. However, there was not a linear increase in risk by probability of exposure, years of night shift work, nor lifetime number of night shifts whether under rotating or permanent work schedules. Risk of lymphoma overall, B cell lymphoma (BCL), its major subtypes other than CLL, and other less prevalent BCL subtypes combined did not show an association., Conclusions: We found conflicting evidence of an association between night shift work and the risk of CLL. We did not observe an association with other lymphoma subtypes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

There are particularly few reports on kidney transplantation after hematopoietic stem cell transplantation (HSCT) for malignant lymphoma, and none of the cases reported a favorable outcome in patients who received kidney transplantation from a different donor to HSCT. In this report, we describe the first case of kidney transplantation from a different donor to HSCT with a successful outcome. Furthermore, we reviewed the previously reported cases. A 59-year-old female patient received an HSCT from her younger brother after chemotherapy for malignant lymphoma. After HSCT, she did not have graft-versus-host disease (GVHD) requiring maintenance treatment. The patient developed chronic kidney disease requiring kidney replacement therapy, probably due to drug toxicity or cardio-renal syndrome. At age 65, she underwent an ABO-compatible, HLA-A, -B, -DR 5/6 mismatched kidney transplantation from her husband. Immunosuppressive therapy with tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab was administered. The patient had urinary tract infections at 7 days, 9 weeks, and 4 months after kidney transplantation, and cytomegalovirus antigenemia at 9 weeks after kidney transplantation, which improved with antibiotic and valganciclovir, respectively. When each infection occurred, we weakened immunosuppressive therapy. Four years after kidney transplantation, the patient is in good clinical condition with a serum creatinine of 1.2 mg/dL, without critical infection or malignancy. In this case, we believe that it was important to optimize the immunosuppressive therapy. In addition, from a review of previous cases, it seemed important that there was no GVHD requiring maintenance therapy in order to prevent excessive immunosuppression., (Copyright © 2022 Elsevier Inc. All rights reserved.)

219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Arsenic in drinking water has been recognized as carcinogenic to humans and can cause solid cancers of lung, urinary bladder, and skin. Positive associations have also been reported between arsenic ingestion and cancers of kidney, liver and prostate. Nevertheless, arsenic trioxide has been used successfully in the treatment of acute promyelocytic leukemia. Therefore, arsenic might play different roles in the carcinogenesis of solid cancers and hematologic malignancies. The relationship between arsenic in drinking water and the incidences of hematologic malignancies has not been fully investigated. We established a cohort of Taiwanese population and assorted 319 townships of Taiwan into two exposure categories using 0.05 mg/L as the cutoff. Then, we linked these data to the Taiwan Cancer Registry and computed standardized incidence ratios (SIRs) of lymphoma and leukemia by sex, exposure category and time period. The trend of changes in the SIRs over time was assessed, from 1981-1990 to 1991-2000 and then to 2001-2010. We found that in both lymphoma and leukemia, the higher exposure category was associated with lower SIRs in both men and women. In terms of time trends, the SIRs in both lymphoma and leukemia showed increasing trends in both sexes, while exposure to arsenic in drinking water decreased over time. The arsenic level in drinking water was negatively associated with the incidences of lymphoma and leukemia in both men and women. This study supports the dual effects of arsenic on carcinogenesis, with a potential protective effect against hematologic malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Li, Cheng and Guo.)

Background: Therapy-related myeloid neoplasms (t-MN) are a leading cause of nonrelapse mortality after autologous peripheral blood stem cell transplantation (aPBSCT) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphomas (NHL). t-MN patients treated at an earlier stage of disease evolution have a better prognosis, and this presents a need to identify patients at risk for t-MN., Methods: Using a prospective longitudinal study design, this study evaluated peripheral blood parameters pre-aPBSCT and on day 100, at 6 months, 1 year, 2 years, and 3 years in 304 patients treated with aPBSCT. The relation between peripheral blood parameters and subsequent development of t-MN was examined, and nomograms were developed to identify patients at risk for t-MN., Results: Twenty-one patients developed t-MN at a median of 1.95 years post-aPBSCT. Hemoglobin, hematocrit, white blood cell, and platelet counts were lower among patients who developed t-MN compared to those who did not; these differences appeared soon after aPBSCT, persisted, and preceded development of t-MN. Older age at aPBSCT (hazard ratio [HR] per&#95;year&#95;increase = 1.08, P = .007), exposure to total body irradiation (TBI) (HR = 2.90, P = .04), and low 100-day platelet count (HR increase&#95;per&#95;unit&#95;decline&#95;in&#95;PLT = 1.01, P = .002) predicted subsequent t-MN. These parameters and primary diagnosis allowed identification of patients at high risk of t-MN (eg, an HL patient undergoing aPBSCT at the age of 70 years with TBI and with a day 100 PLT between 100,000 and 150,000 would have a 62% probability of developing t-MN at 6 years post-aPBSCT)., Conclusions: Abnormalities in peripheral blood parameters can identify patients at high risk for t-MN after aPBSCT for HL or NHL, allowing opportunities to personalize close surveillance and possible disease-modifying interventions., (© 2021 American Cancer Society.)

Few data exist on Epstein-Barr virus (EBV) prevalence across the full spectrum of lymphoma subtypes, particularly in sub-Saharan Africa. The objective of our study was to test the presence of EBV in a nationally representative sample of malignant lymphomas diagnosed in the Butaro Cancer Center of Excellence (BCCOE) in Rwanda. Of 102 Hodgkin (HL) and 378 non-Hodgkin lymphomas (NHL) diagnosed in BCCOE between 2012 and 2018, 52 HL and 207 NHL were successfully tested by EBV-encoding RNA in situ hybridization. EBV prevalence was 54% in HL, being detected in all classical HL subtypes: mixed-cellularity (n = 3/8), nodular-sclerosis (n = 7/17) and lymphocyte-rich (n = 2/3). EBV prevalence was 9% in NHL, being 10% among 158 B-cell NHL, 3% among 35 T-cell NHL and the single NK-cell NHL was EBV-positive. Among B-cell NHL, EBV was present in the majority of Burkitt (n = 8/13), and was also rarely detected in follicular (n = 1/4) and acute B-cell lymphoblastic (n = 1/45) lymphomas. Five of the 45 (11%) diffuse large B-cell lymphomas (DLBCLs) were EBV-positive, including three out of five plasmablastic lymphoma (PBL). Of 39 HL and 163 NHL of known human immunodeficiency virus (HIV) status, 2 (5%) and 14 (9%) were HIV-positive, respectively, of which only four were also EBV-positive (2 PBL, 2 HL). In summary, we report rare regional-level data on the association of EBV with classical HL, Burkitt and DLBCLs, and report sporadic detection in other subtypes possibly related to EBV. Such data inform the burden of disease caused by EBV and can help guide application of future advances in EBV-specific prevention and therapeutics., (© 2021 The World Health Organization. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

We conducted a case-control study of patients from the Clinical Practice Research Datalink in the United Kingdom to describe the trajectories of serum lipid in the years before a diagnosis of lymphoma. Study participants had at least one cholesterol measurement. Multilevel, multivariable linear longitudinal models were fit to examine the adjusted trajectories of serum lipid levels in the years before lymphoma diagnosis. Overall, 11,969 cases of non-Hodgkin lymphoma, 473 of Hodgkin lymphoma, and 61,894 controls were selected. Mean cholesterol levels in the years before the index date showed a more pronounced decrease in the 4 years before lymphoma diagnosis than in controls. Triglycerides levels were unrelated to case status. This research is the first to replicate the results of a similar study conducted in the United States while adjusting for more potential confounders. The newly described different behavior of cholesterol and triglycerides suggests a potential role of cholesterol in lymphomagenesis.

Opinion Statement: The therapeutic armamentarium has significantly expanded since the approval of various CD19-targeting chimeric antigen receptor T cell (CAR-T) therapies in non-Hodgkin lymphoma (NHL). These CAR-Ts are patient-specific and require a complex, resource, and time-consuming process. While this appears promising, autologous CAR-Ts are limited due to the lack of accessibility, manufacturing delays, and variable product quality. To overcome these, allogeneic (allo) CARs from healthy donors appear appealing. These can be immediately available as "off the shelf" ready-to-use products of standardized and superior quality exempt from the effects of an immunosuppressive tumor microenvironment and prior treatments, and potentially with lower healthcare utilization using industrialized scale production. Allogeneic CARs, however, are not devoid of complications and require genomic editing, especially with αβ T cells to avoid graft versus host disease (GvHD) and allo-rejection by the recipient's immune system. Tools for genomic editing such as TALEN and CRISPR provide promise to develop truly "off the shelf" universal CARs and further advance the field of cellular immunotherapy. Several allogeneic CARs are currently in early phase clinical trials, and preliminary data is encouraging. Longer follow-up is required to truly assess the feasibility and safety of these techniques in the patients. This review focuses on the strategies for developing allogeneic CARs along with cell sources and clinical experience thus far in lymphoma., (© 2022. The Author(s).)

Background: In 2020, the United States had approximately 85,000 new diagnoses of Hodgkin and Non-Hodgkin lymphoma. Food insecurity is both a direct and indirect detriment to health outcomes. The rate and risk factors for food insecurity among lymphoma patients are unknown, as the unemployment rate soars far above pre-COVID19 pandemic levels further heightening the economic stresses of a lymphoma diagnosis., Methods: Data regarding the food security status were obtained from the cross-sectional National Health Interview Survey (NHIS) conducted by the Centers for Disease Control and Prevention. A raw score compiled from a series of 10 food security questions was used to determine the Food Secure and Food Insecure groups. Respondents who reported a history of lymphoma from 2011 to 2019 were included in the analysis., Results: Of the 921 patients reporting a history of lymphoma 9.06% were considered Food Insecure. The sociodemographic subgroups with the highest risk of being Food Insecure included respondents living below 100% of the Federal Poverty Level, non-US citizens, the uninsured, and those on Medicare., Conclusion: Food insecurity is common among lymphoma patients. Therefore, oncologists across the country should be aware of the sociodemographic risk factors for food insecurity in order to assist in mediation, maximizing the efficacy of treatments. Research regarding the impact of food insecurity on therapy compliance and patient outcomes is warranted in future studies., (Copyright © 2021. Published by Elsevier Inc.)

Richter syndrome (RS) represents the development of high-grade lymphoma in patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) and presents a diagnostic and therapeutic challenge with an adverse prognosis. The genetic background and morphology of RS in CLL patients treated with chemoimmunotherapy is extensively characterised; however, our knowledge about RS in patients treated with targeted oral therapies should be extended. To understand the morphologic and molecular changes leading to RS in CLL patients treated with the Bruton's tyrosine kinase inhibitor, ibrutinib, and the BCL2 inhibitor, venetoclax, sequential samples from six CLL/SLL patients undergoing RS were collected in both the CLL and RS phases. A detailed immunophenotypic analysis of formalin-fixed, paraffin-embedded tissue specimens of RS phase was performed, followed by extensive molecular characterisation of CLL and RS samples, including the immunoglobulin heavy chain gene (IGH) rearrangement, TP53 mutations, drug-induced resistance mutations in BTK and BCL2 genes and various copy number changes and point mutations detectable with multiplex ligation-dependent probe amplification (MLPA). Rare, non-diffuse large B-cell lymphoma phenotypes of RS were observed in 3/6 cases, including plasmablastic lymphoma and a transitory entity between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. The majority of cases were clonally related and harboured an unmutated variable region of the immunoglobulin heavy chain gene. Abnormalities affecting the TP53 gene occurred in all patients, and every patient carried at least one genetic abnormality conferring susceptibility to RS. In the background of RS, 2/5 patients treated with ibrutinib showed a BTK C481S resistance mutation. One patient developed a BCL2 G101V mutation leading to venetoclax resistance and RS. In conclusion, our findings contribute to better understanding of RS pathogenesis in the era of targeted oral therapies. Rare phenotypic variants of RS do occur under the treatment of ibrutinib or venetoclax, and genetic factors leading to RS are similar to those identified in patients treated with chemoimmunotherapy. To our best knowledge, we have reported the first BCL2 G101V mutation in an RS patient treated with venetoclax., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The anti-cancer potential of dipyridamole has been suggested from experiments, but evidence from population-based studies is still lacking. We aimed to explore if dipyridamole use was related to a lower risk of lymphoid neoplasms. We identified individuals with prescription of aspirin after diagnosis of ischaemic cerebrovascular disease since 2006 by linking several Swedish registers. In these aspirin users, those with dipyridamole prescription were further identified as the study group and patients without dipyridamole were randomly selected as reference group with 1:1 ratio using a propensity score-matching approach. After a median of 6·67 years of follow-up, a total of 46 patients with dipyridamole use developed lymphoid neoplasms with an incidence rate of 0·49 per 1 000 person-years, while the rate in the matched group was 0·74 per 1 000 person-years. As compared to non-users, dipyridamole users were associated with a significantly decreased risk of lymphoid neoplasms [hazard ratio (HR) = 0·65; 95% confidence interval (CI) = 0·43-0·98]. Specifically, the reduced risk was observed for non-Hodgkin lymphomas (HR = 0·64; 95% CI = 0·42-0·94), especially B-cell lymphomas (HR = 0·56; 95% CI = 0·35-0·88). Dipyridamole use was related to a lower risk of lymphoid neoplasms, indicating a clinical potential of dipyridamole to be an adjunct anti-tumour agent against lymphoid neoplasms., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Epidemiological data have provided limited and inconsistent evidence on the relationship between radiation exposure and lymphoid neoplasms. We classified 553 lymphoid neoplasm cases diagnosed between 1950 and 1994 in the Life Span Study cohort of atomic bomb survivors into World Health Organization subtypes. Mature B-cell neoplasms represented 58%, mature T-cell and natural killer (NK)-cell neoplasms 20%, precursor cell neoplasms 5%, and Hodgkin lymphoma (HL) 3%, with the remaining 15% classified as non-Hodgkin lymphoid (NHL) neoplasms or lymphoid neoplasms not otherwise specified. We used Poisson regression methods to assess the relationship between radiation exposure and the more common subtypes. As in earlier reports, a significant dose response for NHL neoplasms as a group was seen for males but not females. However, subtype analyses showed that radiation dose was strongly associated with increased precursor cell neoplasms rates, with an estimated excess relative risk per Gy of 16 (95% Confidence interval: 7.0, >533) at age 50. The current data based primarily of tissue-based diagnoses suggest that the association between radiation dose and lymphoid neoplasms as a group is largely driven by the radiation effect on precursor cell neoplasms while presenting no evidence of a radiation dose response for major categories of mature cell neoplasms, either B- or T-/NK-cell, or more specific disease entities (diffuse large B-cell lymphoma, plasma cell myeloma, adult T-cell leukemia/lymphoma) or HL., (© 2022 by The American Society of Hematology.)