RESUMEN
Primary lymphoma of the central nervous system (PCNSL) is a rare and aggressive form of extranodal non-Hodgkin lymphoma primarily involving the brain, spinal cord, cerebrospinal fluid, and eyes. The role of surgical intervention in PCNSL is currently limited to biopsy and decompression of critical structures if needed - extended resection is debated. Chemotherapy is the mainstay of treatment. In lower and middle-income countries (LMICs), issues like delayed diagnosis and resource constraints are widespread. These guidelines provide a framework for addressing PCNSL in LMICs, emphasizing the importance of early diagnosis, tailored treatment approaches, and ongoing patient monitoring to improve outcomes for this rare and aggressive disease.
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Neoplasias del Sistema Nervioso Central , Países en Desarrollo , Humanos , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias del Sistema Nervioso Central/diagnóstico , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/diagnóstico , Consenso , Guías de Práctica Clínica como AsuntoRESUMEN
Background: Chimeric antigen receptor T cell (CAR-T) is a promising treatment for aggressive Non-Hodgkin lymphoma (NHL). The aim of the meta-analysis was to determine the association between metabolic tumor volumes (MTV) derived on positron emission tomography before CAR-T infusion and the survival of patients with NHL. Methods: Relevant observational studies pertaining to the purpose of the meta-analysis were obtained through a search of PubMed, Web of Science, and Embase from inception of the databases to April 1, 2024. The data was combined using a random-effects model that accounted for the potential influence of between-study heterogeneity. Results: Fifteen observational studies were included. Pooled results showed that compared to those with a lower MTV, the NHL patients with a higher MTV before CAR-T infusion were associated with a poor progression-free survival (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.48 to 2.02, p < 0.001; I2 = 20%) and overall survival (HR: 2.11, 95% CI: 1.54 to 2.89, p < 0.001; I2 = 58%). Subgroup analysis showed that the association between MTV and survival of NHL patients after CAR-T was not significantly impacted by study design, methods for determination of MTV cutoff, or analytic models (univariate or multivariate, p for each subgroup all < 0.05). Subgroup analysis suggested a stronger association between MTV and poor survival outcomes in patients with median of lines of previous treatment of 2 or 3 as compared to those of 4 (p for subgroup difference < 0.05). Further meta-regression analyses suggested that the association between MTV and survival was not significantly affected by sample size, age, proportion of men, cutoff value of MTV, follow-up duration, or study quality scores (p all > 0.05). Conclusion: A high MTV at baseline is associated with a poor survival of NHL patients after CAR-T. Systematic Review Registration: https://inplasy.com/, identifier INPLASY (INPLASY202450069).
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Inmunoterapia Adoptiva , Linfoma no Hodgkin , Humanos , Inmunoterapia Adoptiva/métodos , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patología , Carga Tumoral , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismoRESUMEN
Mediastinal lymphadenopathy has a broad differential diagnosis which includes lymphoma. The current preferred biopsy technique for mediastinal lymph nodes is transbronchial needle aspiration which has mixed results in terms of sensitivity, specificity and diagnostic yields; there are also limitations with subtyping lymphomas with needle aspiration alone which can be a barrier to determine management strategies. Invasive mediastinal lymph node sampling such was with mediastinoscopy provides higher yields and preserved lymph node architecture for both diagnosis and subtyping of lymphoma but carries a higher risk of morbidity and complications. Novel techniques that may increase the diagnostic yield of bronchoscopy in the diagnosis of lymphoma are core biopsy needles, intranodal forcep biopsy, and intranodal cryobiopsy. The evidence is limited due to a relatively small number of cases, so further research is needed to standardize best practices for the bronchoscopic diagnosis of lymphoma. Pleural effusions in lymphoma can be present in up to 30 % of cases with the majority being non-Hodgkins's lymphoma. The presence of exudative effusion in the setting of an existing or prior diagnosis of lymphoma should raise clinical suspicions. Other less common subtypes of lymphoma presenting as primary pleural effusions are explored as well.
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Broncoscopía , Linfoma , Mediastinoscopía , Humanos , Linfoma/diagnóstico , Linfoma/patología , Broncoscopía/métodos , Diagnóstico Diferencial , Mediastinoscopía/métodos , Ganglios Linfáticos/patología , Linfadenopatía/patología , Linfadenopatía/diagnóstico , Mediastino/patología , Derrame Pleural/patología , Derrame Pleural/diagnóstico , Biopsia/métodos , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/patologíaRESUMEN
Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.
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Antígenos CD19 , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Humanos , Masculino , Antígenos CD19/inmunología , Persona de Mediana Edad , Femenino , Inmunoterapia Adoptiva/métodos , Adulto , Receptores Quiméricos de Antígenos/inmunología , Anciano , Linfoma de Células B/terapia , Linfoma de Células B/inmunología , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/inmunologíaRESUMEN
INTRODUCTION: Non-Hodgkin lymphomas (NHLs) encompass a wide range of diseases from precancerous states such as monoclonal B-cell lymphocytosis to the rapidly growing Burkitt lymphoma. In 2022, we witnessed two new classifications for these malignant lymphoid tumors: The World Health Organization (WHO) 5th edition Classification of Haematolymphoid Tumours and the International Consensus Classification of Mature Lymphoid Neoplasms (ICC). AREAS COVERED: Given our improved understanding of the mechanisms underlying lymphomagenesis at the molecular level, several novel agents have been or are being actively developed, including targeted therapies and immunotherapies. Therefore, this review features new and developing first-line pharmacotherapies in NHL. It is organized by the mechanism of action of the drug with the relevant key trials highlighted. EXPERT OPINION: We provide an overview of the development of curative combination chemotherapies for lymphomas, and then discuss the importance of working on a unified classification for these tumors. We discuss resistance to targeted therapies, particularly with the continuous use of Bruton tyrosine kinase inhibitors, how to sequence T-cell therapies (bispecific T-cell engagers and chimeric antigen receptor therapy), and the impact of financial toxicity. We also review possible strategies to increase cure rates at lower costs, with less toxicity, and while promoting global health.
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Antineoplásicos , Linfoma no Hodgkin , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Terapia Molecular Dirigida , Desarrollo de Medicamentos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inmunoterapia/métodos , AnimalesRESUMEN
Fludarabine (FA) is still considered as a first-line chemotherapy drug for hematological tumors related to B lymphocytes. However, it is worth noting that the non-specific distribution and non-different cytotoxicity of FA may lead to irreversible consequences such as central nervous system damage such as blindness, coma, and even death. Therefore, it is very important to develop a system to targeting delivery FA. In preliminary studies, it was found that B lymphoma cells would specific highly expressing the sialic acid-binding immunoglobulin-like lectin 2 (known as CD22). Inspired by the specific recognition of sialic acid residues and CD22, we have developed a supramolecular prodrug based on polysialic acid, an endogenous biomacromolecule, achieving targeted-therapy of B-cell non-Hodgkin's lymphoma (B-NHL). Specifically, the prepared hydrophobic reactive oxygen species-responsive FA dimeric prodrug (F2A) interacts with the TPSA, which polysialic acid were modified by the thymidine derivatives, through non-covalent intermolecular interactions similar to "Watson-Crick" base pairing, resulting in the formation of nanoscale supramolecular prodrug (F@TPSA). Cell experiments have confirmed that F@TPSA can be endocytosed by CD22+ B lymphoma cells including Raji and Ramos cells, and there is a significant difference of endocytosis in other leukocytes. Furthermore, in B-NHL mouse model, compared with FA, F@TPSA is determined to have a stronger tumor targeting and inhibitory effect. More importantly, the distribution of F@TPSA in vivo tends to be enriched in lymphoma tissue rather than nonspecific, thus reducing the leukopenia of FA. The targeted delivery system based on PSA provides a new prodrug modification strategy for targeted treatment of B-NHL.
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Linfoma de Células B , Profármacos , Profármacos/química , Profármacos/farmacología , Animales , Ratones , Humanos , Línea Celular Tumoral , Linfoma de Células B/tratamiento farmacológico , Ácidos Siálicos/química , Ácidos Siálicos/farmacología , Lectina 2 Similar a Ig de Unión al Ácido Siálico , Antineoplásicos/farmacología , Antineoplásicos/química , Nanopartículas/química , Medicina de Precisión/métodos , Sistemas de Liberación de Medicamentos/métodos , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno/metabolismo , Linfoma no Hodgkin/tratamiento farmacológicoRESUMEN
BACKGROUND/AIM: Non-B non-Hodgkin lymphomas (NHL) represent over 30 T/NK lymphoma types. The majority of them are T-cell lymphoblastic lymphomas (TLL) and anaplastic large cell lymphomas (ALCL). Other rare non-B NHLs represent a diverse group of neoplasms, usually excluded from clinical trials. This study analyzed outcomes in pediatric patients with non-B NHL in a single oncology center with particular emphasis on patients with rare NHLs. PATIENTS AND METHODS: We retrospectively analyzed data from patients <18 years with newly diagnosed non-B NHL treated at the Department of Pediatric Hematology and Oncology in Bydgoszcz between 2002 and 2022. The probability of 5-year overall survival (pOS) and event-free survival (pEFS) were calculated for the entire cohort and patients with TLL and ALCL. The clinical course for patients with rare non-B NHL was described in detail. RESULTS: Twenty-six children were eligible for analysis. Fourteen patients were diagnosed with ALCL, nine with TLL, and three with rare NHL types (subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma and hydroa vacciniforme-like lymphoproliferative disease associated lymphoma). For the entire group, the 5-year pOS was 83.7% and the 5-year pEFS was 72.4%. For TLL and ALCL, the outcomes were comparable with those achieved in clinical trials. Patients with rare NHL were treated according to individualized therapy recommendations based on physicians' expertise and available case report descriptions. CONCLUSION: There is a lack of knowledge on optimal therapeutic strategies for rare NHLs. It is crucial to create trials dedicated to uncommon NHLs and establish therapy guidelines for these patients.
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Linfoma no Hodgkin , Humanos , Niño , Masculino , Femenino , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/tratamiento farmacológico , Adolescente , Preescolar , Estudios Retrospectivos , Resultado del Tratamiento , Manejo de la Enfermedad , Pronóstico , Oncología Médica/métodosRESUMEN
Introduction: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. Methods: CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Results: Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. Discussion: This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.
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Biomarcadores de Tumor , Neoplasias Encefálicas , Proteómica , Humanos , Proteómica/métodos , Biomarcadores de Tumor/líquido cefalorraquídeo , Neoplasias Encefálicas/líquido cefalorraquídeo , Neoplasias Encefálicas/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Diagnóstico Diferencial , Adulto , Linfoma no Hodgkin/líquido cefalorraquídeo , Linfoma no Hodgkin/diagnósticoRESUMEN
BACKGROUND: Non-Hodgkin lymphoma (NHL) has been identified as a significant contributor to the cancer burden. This study investigates the incidence, mortality, and survival trends of NHL cancer in Brunei Darussalam from 2011 to 2020. METHODS: This is a registry-based retrospective study using de-identified data from the Brunei Darussalam Cancer Registry on patients diagnosed with NHL from 2011 to 2020 based on the ICD-10 codes C82-86. Statistical methods include descriptive statistics, age-specific and age-standardised incidence (ASIR) and mortality rates (ASMR), and joinpoint regression for trend analysis. Survival analysis was conducted using Kaplan-Meier plots, log-rank test, and Cox Proportional Hazards regression. RESULTS: From 2011 to 2020, 330 patients were diagnosed with NHL. The majority of patients were males (51.8%) and of Malay descent (82.7%). The age group most diagnosed was 55-74 years (42.3%), with a mean age at diagnosis being 55.1 years. The ASIRs were 12.12 for males and 10.39 per 100,000 for females; ASMRs were 6.11 for males and 4.76 per 100,000 for females. Diffuse large B-cell lymphoma was the most prevalent subtype, accounting for 39.1% of cases. The overall 5-year survival rate was 61.2%, with lower rates observed in older patients and those diagnosed at distant metastasis stage. Furthermore, older age and advanced stage diagnosis significantly increased mortality risk. NHL incidence and mortality rates in Brunei Darussalam remain stable over the period of 10 years, but highlights significant disparities in gender and age. CONCLUSIONS: The findings emphasize the importance of early detection and tailored treatments, especially for high-risk groups, in managing NHL's burden. These insights underline the need for focused healthcare strategies and continued research to address NHL's challenges.
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Linfoma no Hodgkin , Humanos , Masculino , Femenino , Brunei/epidemiología , Linfoma no Hodgkin/epidemiología , Linfoma no Hodgkin/mortalidad , Persona de Mediana Edad , Incidencia , Anciano , Estudios Retrospectivos , Adulto , Adulto Joven , Sistema de Registros , Anciano de 80 o más Años , Adolescente , Niño , Preescolar , Lactante , Tasa de SupervivenciaRESUMEN
BACKGROUND: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard treatment for relapsed/refractory lymphoma patients. Yet, the widespread use of BEAM is hindered by carmustine accessibility. This study evaluates the efficacy and safety of PEAM (Cisplatin, Etoposide, Cytarabine, and Melphalan) versus BEAM in auto-HSCT for Hodgkin (HL) and non-Hodgkin lymphoma (NHL) patients. METHODS: We conducted a retrospective single-center study of adult lymphoma patients who received PEAM or BEAM pretransplant conditioning between January 2004 to December 2022, comparing efficacy and safety outcomes. RESULTS: Among 143 patients (median age of 33 years, 58% males), 55 had HL, and 88 had NHL. The overall response rate (ORR) was 86.7% for PEAM and 72.3% for BEAM, and the relapse rate (RR) was lower for PEAM than BEAM (22.9% vs 45.6%). Median time to relapse (TTR) and overall survival (OS) were not reached for either group. PEAM exhibited a shorter time to both neutrophil (NE) and platelet (PE) engraftment compared to BEAM (10 vs 12 days), with a more tolerable gastrointestinal (GI) toxicity profile. CONCLUSIONS: Both BEAM and PEAM showed similar outcomes, demonstrating comparable efficacy in terms of ORR, TTR, and OS for both HL and NHL patients. However, PEAM-conditioning was associated with a shorter time to engraftment and fewer GI adverse events.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carmustina , Cisplatino , Citarabina , Trasplante de Células Madre Hematopoyéticas , Melfalán , Acondicionamiento Pretrasplante , Trasplante Autólogo , Humanos , Adulto , Masculino , Femenino , Carmustina/administración & dosificación , Carmustina/uso terapéutico , Estudios Retrospectivos , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Adulto Joven , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/mortalidad , Etopósido/administración & dosificación , Linfoma/terapia , Linfoma/mortalidad , Adolescente , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/mortalidad , Resultado del TratamientoRESUMEN
Immune dysregulation in autoimmune diseases (ADs) is a risk factor for the development of Non-Hodgkin's lymphoma (NHL). However, the underlying mechanisms are not well understood. Hence, this retrospective study aims to describe the clinical and demographic factors that increase the risk of NHL development in patients with ADs. Our study utilised data from National Inpatient Sample (NIS) for the duration of 2016-2020 on all adult patients aged > 18 years who had NHL. We divided them into two cohorts: one with underlying ADs and one without underlying ADs. We then compared the adjusted odds ratios (aOR) of various risk factors. It was found that 0.9% of autoimmune cases had NHL, while 0.7% of non-autoimmune cases had NHL. Among those with autoimmune conditions, various factors influenced the presence of lymphoma, such as personal history of chemotherapy or radiation, family history of lymphoid malignancy, HIV infection, advanced age of 60-69 years, Asian and Pacific Islander ethnicity and viral hepatitis. The increased risk of NHL with autoimmune conditions is well established. Studies have also shown that these patients can overall have a poor prognosis from their NHL when compared to patients without autoimmune diseases. However, there is limited literature regarding the interplay of traditional NHL risk factors with underlying autoimmunity. Hence, our study sheds light on the lesser studied risk factors, such as patient characteristics and comorbidities.
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Enfermedades Autoinmunes , Bases de Datos Factuales , Linfoma no Hodgkin , Humanos , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/complicaciones , Linfoma no Hodgkin/epidemiología , Linfoma no Hodgkin/etiología , Persona de Mediana Edad , Factores de Riesgo , Femenino , Anciano , Masculino , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Adolescente , Adulto JovenRESUMEN
OBJECTIVES: The Seveso accident (1976) caused the contamination with 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in an area north of Milan, Italy. We report the results of the update of mortality and cancer incidence in the exposed population through 2013. METHODS: The study cohort includes subjects living in three contaminated zones with decreasing TCDD soil concentrations (zone A, B and R) and in a surrounding uncontaminated territory (reference). Poisson models stratified/adjusted for gender, age and period were fitted to calculate rate ratios (RRs) and 95% CIs. RESULTS: In zone A in males, we found elevated mortality from circulatory diseases in the first decade after the accident (17 deaths, RR 2.00, 95% CI 1.24 to 3.23). In females, mortality from diabetes mellitus was increased, with a positive trend across zones. Incidence of soft tissue sarcoma was increased in males in zone R in the first decade (6 cases, RR 2.62, 95% CI 1.01 to 6.83). In females in zone B, there was an excess of non-Hodgkin's lymphoma after 30 years (6 cases, RR 2.87, 95% CI 1.14 to 7.23). Multiple myeloma was increased in the second decade in females in zone B (4 cases, RR 5.09, 95% CI 1.82 to 14.2) and in males in zone R (11 cases, RR 2.15, 95% CI 1.08 to 4.26). In males in zone R, there was a leukaemia excess after 30 years (23 cases, RR 2.02, 95% CI 1.04 to 3.93). CONCLUSIONS: Although with different patterns across gender, zone and time, we confirmed previous results of increased cardiovascular diseases, diabetes, soft tissue sarcoma, and lymphatic and haematopoietic cancers.
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Exposición a Riesgos Ambientales , Neoplasias , Dibenzodioxinas Policloradas , Humanos , Masculino , Italia/epidemiología , Femenino , Incidencia , Neoplasias/epidemiología , Neoplasias/mortalidad , Neoplasias/etiología , Persona de Mediana Edad , Adulto , Exposición a Riesgos Ambientales/efectos adversos , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus/epidemiología , Sarcoma/epidemiología , Sarcoma/mortalidad , Sarcoma/inducido químicamente , Adulto Joven , Linfoma no Hodgkin/epidemiología , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/inducido químicamente , Liberación de Peligros Químicos/estadística & datos numéricos , Estudios de Cohortes , Adolescente , Contaminantes del Suelo/efectos adversos , Contaminantes del Suelo/análisisRESUMEN
Background/Aims: Inflammatory bowel disease (IBD) may contribute to the development of hematologic malignancies. In this study, the potential relationship between IBD and hematologic malignancies was investigated. Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for all cohort studies comparing the incidence of hematologic malignancies in non-IBD populations with that in IBD patients, and we extracted relevant data from January 2000 to June 2023 for meta-analysis. Results: Twenty cohort studies involving 756,377 participants were included in this study. The results showed that compared with the non-IBD cohort, the incidence of hematologic malignancies in the IBD cohort was higher (standardized incidence ratio [SIR]=3.05, p<0.001). According to the specific types of IBD, compared with the non-IBD patients, the incidences of hematologic malignancies in ulcerative colitis patients (SIR=2.29, p=0.05) and Crohn's disease patients (SIR=3.56, p=0.005) were all higher. In the subgroup analysis of hematologic malignancy types, compared with the control group, the incidences of non-Hodgkin's lymphoma (SIR=1.70, p=0.01), Hodgkin's lymphoma (SIR=3.47, p=0.002), and leukemia (SIR=3.69, p<0.001) were all higher in the IBD cohort. Conclusions: The incidence of hematologic malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and leukemia is higher in patients with IBD (ulcerative colitis or Crohn's disease) than in non-IBD patients.
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Neoplasias Hematológicas , Enfermedades Inflamatorias del Intestino , Humanos , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/etiología , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Incidencia , Estudios de Cohortes , Masculino , Femenino , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/epidemiología , Factores de Riesgo , Adulto , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Persona de Mediana Edad , Linfoma no Hodgkin/epidemiología , Linfoma no Hodgkin/etiologíaRESUMEN
INTRODUCTION: Considering the notable advances made in the treatment of lymphoma, assessment of health-related quality of life (HRQoL) of lymphoma patients has become a critical aspect to consider both in clinical research and routine practice. However, there is paucity of information about lymphoma specific HRQoL profile at diagnosis. PATIENTS AND METHODS: HRQoL at diagnosis was assessed for 3922 adult patients with newly diagnosed high-grade (HG) (n = 1994), low-grade (LG) (n = 1053) non-Hodgkin (NHL) and Hodgkin (HL) (n = 875) lymphomas included in REal world dAta in LYmphoma and Survival in Adults (REALYSA, NCT03869619), a prospective non-interventional multicentric cohort in France. Disease-specific HRQoL aspects were assessed with three validated EORTC questionnaires, namely, the QLQ-NHL-HG29, the QLQ-NHL-LG20 and the QLQ-HL27, for patients with NHL-HG, NHL-LG and HL, respectively. RESULTS: We confirmed the high-level of completion of these questionnaires in REALYSA cohort, ranging from 84 % for QLQ-HG29 to 88 % for QLQ-HL27. The proportion of patients with impaired global health status was as follows: T-cell NHL, 67 %; diffuse large B-cell (DLBCL), 62 %; Burkitt, 61 %; HL, 53 %; marginal zone, 49 %; mantle cell, 48 %; follicular, 47 %. Multivariable regression analyses for DLBCL, follicular and HL showed that gender, performance status and B symptoms were independently associated with all HRQoL dimensions. However, a variable effect of age and stage were observed among these three subtypes. CONCLUSIONS: A comprehensive analysis was made describing the HRQoL profile of newly diagnosed patients with different types of lymphomas. Our data may help to enhance the interpretation of HRQoL results in future studies using the recently validated EORTC lymphoma specific questionnaires.
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Enfermedad de Hodgkin , Linfoma no Hodgkin , Calidad de Vida , Humanos , Enfermedad de Hodgkin/psicología , Masculino , Femenino , Persona de Mediana Edad , Linfoma no Hodgkin/psicología , Francia/epidemiología , Adulto , Anciano , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto Joven , Adolescente , Estado de Salud , Anciano de 80 o más AñosRESUMEN
Currently, Non-Hodgkin Lymphoma (NHL) constitutes 85-90 % of all lymphomas. Clinical treatment of NHL is based on the "4-drug regimen" known as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Rituximab (RTX) is added to increase the effectiveness and selectivity of the treatment and is the first-line standard treatment for NHL patients. However, success is often prevented by the development of drug resistance. In this study, it was aimed to overcome drug resistance by using two novel tumor-targeted derivatives: guanidine-amphiphilic cyclodextrin (ACD) and guanidine-cyclodextrin polymer (PCD) nanoparticles (NP). These constructs display promise in overcoming drug resistance and enhancing the effectiveness of R-CHOP treatment while potentially eliminating the need for corticosteroid. NP were found to be smaller than 200 nm by dynamic light scattering (DLS). Hemolytic activity and cytotoxicity data on L929 cells demonstrated the safety of the newly synthesized CD derivatives. Additional in vitro characterization studies, including surface charge, physical stability, drug loading capacity, drug release profile, and imaging, as well as conventional and 3D cell culture studies were carried out. Compared to drug solutions, the viability of Daudi human lymphoma cells was statistically significantly decreased in both drug-loaded ACD and PCD NP formulations (p < 0.05). Additionally, RTX-conjugated and drug-loaded ACD NPs exhibited the lowest cell viability due to RTX dependent cytotoxicity.
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Supervivencia Celular , Ciclodextrinas , Liberación de Fármacos , Linfoma no Hodgkin , Nanopartículas , Rituximab , Linfoma no Hodgkin/tratamiento farmacológico , Humanos , Rituximab/administración & dosificación , Rituximab/química , Nanopartículas/química , Línea Celular Tumoral , Ciclodextrinas/química , Animales , Supervivencia Celular/efectos de los fármacos , Ratones , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Doxorrubicina/química , Vincristina/administración & dosificación , Vincristina/farmacología , Vincristina/química , Prednisona/administración & dosificación , Prednisona/química , Prednisona/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/química , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Portadores de Fármacos/química , Tamaño de la Partícula , CelulosaRESUMEN
Introduction: Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency. Methods: We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity. Results: From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026). Discussion: As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.
Asunto(s)
Antígenos CD19 , Ciclofosfamida , Inmunoterapia Adoptiva , Linfoma no Hodgkin , Vidarabina , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Masculino , Persona de Mediana Edad , Femenino , Antígenos CD19/inmunología , Vidarabina/análogos & derivados , Vidarabina/administración & dosificación , Vidarabina/uso terapéutico , Estudios Retrospectivos , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/inmunología , Anciano , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Adulto , Depleción Linfocítica/métodos , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Productos Biológicos/administración & dosificación , Receptores de Antígenos de Linfocitos TRESUMEN
To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage â ¢ to â £. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.
Asunto(s)
Perforación Intestinal , Humanos , Masculino , Femenino , Niño , Estudios Retrospectivos , Adolescente , Preescolar , Lactante , Pronóstico , Perforación Intestinal/etiología , Linfoma de Células B , Linfoma de Burkitt , Tracto Gastrointestinal , Linfoma no Hodgkin , Linfoma de Células B Grandes DifusoRESUMEN
This case report delves into the intricate medical history of an 85-year-old male who experienced a myriad of health challenges throughout his years. With a medical history full of conditions, such as stroke, sinus bradycardia, chronic obstructive pulmonary disease, severe pulmonary hypertension, and chronic gastritis, the patient´s health profile is further complicated by prostatic hypertrophy, persistent dorsalgia and lumbalgia, the presence of a thyroid nodule, and a recent onset of hypothyroidism. Among the diverse medical conditions of this patient, our narrative is primarily centered on his latest diagnosis: non-Hodgkin´s lymphoma. Non-Hodgkin´s lymphoma is not just a mere addition to his already complex medical history; it is a malignant neoplasm that shapes worldwide patterns of cancer mortality. The first indicators that led to this discovery were the patient´s complaints of persistent pain in the left lateral neck region associated with dysphagia. This was not an isolated symptom; the patient also reported a month-long history of asthenia, myalgias, weakness around the pelvic girdle, fatigue, and hyporexia, depicting a concerning clinical picture. Advanced diagnostic tools, namely ultrasound and computed tomography, shed light on submaxillary and cervical adenopathies. To corroborate such findings and get a definitive diagnosis of malignancy, a fine-needle aspiration was advised. Through this case, we aim not only to describe a clinical scenario but to highlight the challenges involved in the diagnosing and treatment of non-Hodgkin ´s lymphoma, especially in elderly patients. The overlap of multiple comorbidities adds further complexity to the scene, demanding meticulous care and expertise. This report serves as an educational tool for oncology experts, as well as testimony to the complexities of patient care in the oncology diagnostic and treatment setting.
Este reporte de caso se centra en el intricado historial médico de un varon de 85 años que experimenta una miriada de problemas de salud a lo largo de sus años. Con un historial médico lleno de afecciones, como accidente cerebrovascular, bradicardia sinusal, enfermedad pulmonar obstructiva crónica, hipertensión pulmonar grave y gastritis crónica, el perfil de salud del paciente se complica aún más por la presencia de hipertrofia prostática, dorsalgia y lumbalgia persistentes, la presencia de un nódulo tiroideo y el reciente diagnóstico de hipotiroidismo. Entre las diversas afecciones de este paciente, nuestra narración se centra principalmente en su último diagnóstico: linfoma no Hodgkin. El linfoma no hodgkiniano no es un mero añadido a su ya complejo historial médico; es una neoplasia maligna que configura las tendencias de mortalidad por cáncer a nivel mundial. Los primeros indicadores que llevaron a este descubrimiento fueron las quejas del paciente por dolor persistente en la región lateral izquierda del cuello, asociado a disfagia. No se trataba de un síntoma aislado, ya que el paciente también refería desde hacía un mes astenia, mialgias, debilidad alrededor de la cintura pélvica, fatiga e hiporexia, lo que describía un cuadro clínico preocupante. Las herramientas diagnósticas avanzadas, a saber, la ecografía y la tomografía computarizada, arrojaron luz sobre las adenopatías submaxilares y cervicales. revelaron sobre las adenopatías submaxilares y cervicales.
Asunto(s)
Linfoma no Hodgkin , Humanos , Masculino , Anciano de 80 o más Años , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/terapia , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin's lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale. METHODS: Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10. RESULTS: Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling (n = 14), fatigue (n = 11), and pain (n = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms. CONCLUSIONS: This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL.
Asunto(s)
Medición de Resultados Informados por el Paciente , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Reproducibilidad de los Resultados , Linfoma de Células B/diagnóstico , Calidad de Vida , Anciano de 80 o más Años , Fatiga/etiología , Linfoma no Hodgkin/diagnósticoRESUMEN
BACKGROUND: Spinal cord compression is a rare presentation of non-Hodgkin lymphoma (NHL) in children. We aimed to describe the prevalence, histological subtypes, clinical presentation, therapy, and outcome of those children in a population-based cohort. The chemotherapy regimen remained comparable over time. METHODS: We retrospectively identified all children and adolescents with paresis as initial manifestations of the NHL between January 1990 and December 2020 from the NHL-BFM database. Characteristics, therapy, and outcome data were gathered from the database and patient files. RESULTS: Fifty-seven of 4779 children (1.2%) presented with initial paresis due to spinal cord compression. The median age was 10.3 years (range, 3.1-18.0 years), and 33% were female. Initial symptoms were paresis/weakness (n = 50, 88%), back pain (n = 33, 58%), paresthesia (n = 23, 40%), and bladder dysfunction and/or constipation (n = 22, 39%), persisting for a median of 14 days before diagnosis. Subtype distribution was mature B-NHL (n = 41, 72%), precursor B-lymphoblastic lymphoma (LBL) (n = 12, 21%), anaplastic large cell lymphoma (ALCL) (n = 3, 5%), and T-LBL (n = 1, 2%). Initial emergency therapy included surgery (70%) and/or chemotherapy/steroids (63%). Five-year event-free survival and overall survival (80% ± 5% and 82% ± 5%, respectively) were comparable with all other NHL patients. Neurological symptoms persisted in approximately one-third of surviving patients at the last follow-up. CONCLUSION: 1.2% of pediatric NHL patients presented with paresis from spinal cord compression mainly due to B-cell lymphomas. Neurological sequelae were observed in one-third of surviving patients.