RESUMEN
BACKGROUND: There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. AIMS: The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. METHODS: We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population-based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random-effects meta-analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21-1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06-1.53]) and non-Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20-1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27-1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09-1.35]) (p for interaction = 0.026). Meta-regression demonstrated that mean age of patients, study year, mean study follow-up duration, and percentages of immunomodulators and biologics use did not influence study outcome. CONCLUSIONS: The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non-Hodgkin's lymphoma.
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Enfermedades Inflamatorias del Intestino , Linfoma , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Linfoma/epidemiología , Linfoma/etiología , Factores de Riesgo , Estudios de Cohortes , Linfoma no Hodgkin/epidemiología , Linfoma no Hodgkin/etiología , Enfermedad de Hodgkin/epidemiologíaRESUMEN
BACKGROUND: A major update to the International Nuclear Workers Study (INWORKS) was undertaken to strengthen understanding of associations between low-dose exposure to penetrating forms of ionising radiation and mortality. Here, we report on associations between radiation dose and mortality due to haematological malignancies. METHODS: We assembled a cohort of 309â932 radiation-monitored workers (269â487 [87%] males and 40â445 [13%] females) employed for at least 1 year by a nuclear facility in France (60â697 workers), the UK (147â872 workers), and the USA (101â363 workers). Workers were individually monitored for external radiation exposure and followed-up from Jan 1, 1944, to Dec 31, 2016, accruing 10·72 million person-years of follow-up. Radiation-mortality associations were quantified in terms of the excess relative rate (ERR) per Gy of radiation dose to red bone marrow for leukaemia excluding chronic lymphocytic leukaemia (CLL), as well as subtypes of leukaemia, myelodysplastic syndromes, non-Hodgkin and Hodgkin lymphomas, and multiple myeloma. Estimates of association were obtained using Poisson regression methods. FINDINGS: The association between cumulative dose to red bone marrow, lagged 2 years, and leukaemia (excluding CLL) mortality was well described by a linear model (ERR per Gy 2·68, 90% CI 1·13 to 4·55, n=771) and was not modified by neutron exposure, internal contamination monitoring status, or period of hire. Positive associations were also observed for chronic myeloid leukaemia (9·57, 4·00 to 17·91, n=122) and myelodysplastic syndromes alone (3·19, 0·35 to 7·33, n=163) or combined with acute myeloid leukaemia (1·55, 0·05 to 3·42, n=598). No significant association was observed for acute lymphoblastic leukaemia (4·25, -4·19 to 19·32, n=49) or CLL (0·20, -1·81 to 2·21, n=242). A positive association was observed between radiation dose and multiple myeloma (1·62, 0·06 to 3·64, n=527) whereas minimal evidence of association was observed between radiation dose and non-Hodgkin lymphoma (0·27, -0·61 to 1·39, n=1146) or Hodgkin lymphoma (0·60, -3·64 to 4·83, n=122) mortality. INTERPRETATION: This study reports a positive association between protracted low dose exposure to ionising radiation and mortality due to some haematological malignancies. Given the relatively low doses typically accrued by workers in this study (16 mGy average cumulative red bone marrow dose) the radiation attributable absolute risk of leukaemia mortality in this population is low (one excess death in 10â000 workers over a 35-year period). These results can inform radiation protection standards and will provide input for discussions on the radiation protection system. FUNDING: National Cancer Institute, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Institut de Radioprotection et de Sûreté Nucléaire, Orano, Electricité de France, UK Health Security Agency. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
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Mieloma Múltiple , Exposición Profesional , Radiación Ionizante , Humanos , Mieloma Múltiple/mortalidad , Masculino , Exposición Profesional/efectos adversos , Femenino , Estudios de Cohortes , Persona de Mediana Edad , Adulto , Linfoma/mortalidad , Linfoma/etiología , Neoplasias Inducidas por Radiación/mortalidad , Neoplasias Inducidas por Radiación/etiología , Leucemia/mortalidad , Francia/epidemiología , Exposición a la Radiación/efectos adversos , Estados Unidos/epidemiologíaRESUMEN
The concept of time toxicity in oncology refers to the presence of frequent healthcare-related interactions that can interfere with patient well-being. In this review, we examine several manifestations of time toxicity in non-Hodgkin lymphoma and multiple myeloma and discuss their impact on decision-making with patients. For example, time toxicity may influence the choice of chemoimmunotherapy versus lenalidomide-rituximab in follicular lymphoma. In myeloma, it may inform the optimal dosing schedule for proteasome inhibitors and bisphosphonates. In both malignancies, varying time toxicity profiles are a key distinction between chimeric antigen receptor T-cell therapies and bispecific antibodies. We outline the challenges with measuring time toxicity as a trial endpoint but discuss its importance as a consideration for patient care, both in standard-of-care settings and in clinical trials. Throughout the review, we highlight strategies to lower the time toxicity of therapies in lymphoma and myeloma without compromising their efficacy or patient safety.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Manejo de la Enfermedad , Linfoma/terapia , Linfoma/diagnóstico , Linfoma/etiología , Linfoma/tratamiento farmacológico , Factores de Tiempo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodosRESUMEN
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.
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Microbioma Gastrointestinal , Linfoma , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Microbioma Gastrointestinal/genética , Linfoma/genética , Linfoma/etiología , Linfoma/microbiología , Predisposición Genética a la EnfermedadRESUMEN
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.
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Leucemia , Linfoma , Humanos , Niño , Irán/epidemiología , Masculino , Leucemia/epidemiología , Leucemia/etiología , Femenino , Linfoma/epidemiología , Linfoma/etiología , Linfoma/inducido químicamente , Preescolar , Adolescente , Estudios de Casos y Controles , Lactante , Exposición a Riesgos Ambientales/efectos adversos , Factores de Riesgo , Oportunidad Relativa , IncidenciaRESUMEN
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.
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Leucemia Linfocítica Crónica de Células B , Linfoma , Mieloma Múltiple , Trastornos Mieloproliferativos , Policitemia Vera , Trombocitemia Esencial , Humanos , Trombocitemia Esencial/tratamiento farmacológico , Trombocitemia Esencial/epidemiología , Estudios Retrospectivos , Japón/epidemiología , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/epidemiología , Trastornos Mieloproliferativos/diagnóstico , Linfoma/epidemiología , Linfoma/etiología , Linfoma/terapiaRESUMEN
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.
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Enfermedades Inflamatorias del Intestino , Linfoma , Humanos , Linfoma/etiología , Linfoma/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Factores de Riesgo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
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.
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Neoplasias del Sistema Nervioso Central , Terapia Molecular Dirigida , Humanos , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/diagnóstico , Terapia Molecular Dirigida/métodos , Transducción de Señal/efectos de los fármacos , Linfoma/terapia , Linfoma/tratamiento farmacológico , Linfoma/diagnóstico , Linfoma/patología , Linfoma/genética , Linfoma/etiología , Manejo de la EnfermedadRESUMEN
PURPOSE: This study aimed to assess the long-term risks associated with a history of infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV). Specifically analyzing the potential increase in developing nasopharyngeal cancer (NPC) and lymphoma in patients with a history of IM and exploring the prevalence of other EBV-associated conditions. MATERIALS AND METHODS: The Korean National Health Insurance Service (NHIS) database was utilized for a retrospective analysis, covering data from 2002 to 2021. A total of 25,582 IM patients and controls were included, with 1:1 propensity score matching. The study monitored outcomes, including lymphoma, NPC, gastric cancer, multiple sclerosis, and all-cause mortality. RESULTS: Patients with a history of IM demonstrated a significantly higher incidence of lymphoma (hazard ratio [HR], 5.320; 95% confidence interval [CI], 3.208 to 8.820; p < 0.001) and NPC (HR, 7.116; 95% CI, 1.617 to 31.314; p=0.009) during the follow-up period compared with the control group. Additionally, the IM group showed an increased rate of all-cause mortality (HR, 2.225; 95% CI, 1.858 to 2.663; p < 0.001). CONCLUSION: This study suggests that individuals with a history of IM have an elevated risk of developing lymphoma and NPC in South Korea, emphasizing the importance of vigilant follow-up and monitoring. The results advocate for heightened awareness and potential national monitoring policies to address the long-term health implications of EBV infection and to implement preventive measures.
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Mononucleosis Infecciosa , Linfoma , Carcinoma Nasofaríngeo , Humanos , Masculino , Femenino , República de Corea/epidemiología , Mononucleosis Infecciosa/epidemiología , Mononucleosis Infecciosa/complicaciones , Estudios Retrospectivos , Carcinoma Nasofaríngeo/epidemiología , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/etiología , Persona de Mediana Edad , Adulto , Linfoma/epidemiología , Linfoma/etiología , Incidencia , Factores de Riesgo , Programas Nacionales de Salud/estadística & datos numéricos , Adulto Joven , Herpesvirus Humano 4 , Neoplasias Nasofaríngeas/epidemiología , Neoplasias Nasofaríngeas/etiología , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/virología , Anciano , Adolescente , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiologíaRESUMEN
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.
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Relación Dosis-Respuesta en la Radiación , Linfoma , Neoplasias Inducidas por Radiación , Animales , Ratones , Neoplasias Inducidas por Radiación/etiología , Neoplasias Inducidas por Radiación/patología , Linfoma/etiología , Linfoma/patología , Neoplasias/radioterapia , Neoplasias/patología , Neoplasias/etiología , Exposición a la Radiación/efectos adversos , Dosis de Radiación , Femenino , MasculinoRESUMEN
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.
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Hematopoyesis Clonal , Trasplante de Células Madre Hematopoyéticas , Mutación , Neoplasias Primarias Secundarias , Trasplante Autólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Trasplante Autólogo/efectos adversos , Adulto , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/terapia , Anciano , Pronóstico , Trastornos Mieloproliferativos/terapia , Trastornos Mieloproliferativos/etiología , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/patología , Adulto Joven , Adolescente , Proteína Fosfatasa 2C/genética , Proteína p53 Supresora de Tumor/genética , Estudios de Seguimiento , Linfoma/terapia , Linfoma/etiología , Linfoma/genética , Tasa de SupervivenciaRESUMEN
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.
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Modelos Animales de Enfermedad , Animales , Humanos , Infecciones por VIH/complicaciones , Linfoma Relacionado con SIDA , Linfoma/virología , Linfoma/etiología , RatonesRESUMEN
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.
Inflammatory pathways directly or indirectly regulate the TME and are closely related to the development of lymphoma.This review was conducted to elucidate the connection between inflammatory pathways and the tumorigenesis and drug resistance of several common lymphomas.Overall, targeting abnormally activated molecules upstream and downstream of lymphoma inflammatory pathways in the future is expected to be a new target for lymphoma treatment.
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Linfoma , Humanos , Linfoma/etiología , Linfoma/metabolismo , Transformación Celular Neoplásica , Microambiente TumoralRESUMEN
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.
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Herpesvirus Humano 8 , Linfoma , Humanos , Linfoma/etiología , Virus OncogénicosRESUMEN
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.
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Inflamasomas , Linfoma , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamación/metabolismo , Linfoma/etiología , Linfoma/terapia , Microambiente TumoralRESUMEN
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.
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Leucemia , Linfoma , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/genética , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T , Inmunoterapia Adoptiva/métodos , Leucemia/genética , Leucemia/terapia , Linfoma/etiología , Microambiente TumoralRESUMEN
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.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Linfoma , Neoplasias Primarias Secundarias , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Leucemia Mieloide Aguda/terapia , Linfoma/etiología , Linfoma/terapia , Recurrencia , Acondicionamiento Pretrasplante , Neoplasias Primarias Secundarias/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
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.
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Linfoma , Sarcoidosis , Humanos , Sarcoidosis/complicaciones , Sarcoidosis/terapia , Linfoma/etiología , Linfoma/terapiaRESUMEN
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.
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Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Linfoma , Trastornos Linfoproliferativos , Humanos , Niño , Adulto Joven , Adulto , Adolescente , Recién Nacido , Lactante , Preescolar , Incidencia , Estudios de Cohortes , Infecciones por Virus de Epstein-Barr/complicaciones , Linfoma/epidemiología , Linfoma/etiología , Linfoma/terapia , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Proliferación Celular , Estudios RetrospectivosRESUMEN
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.