RESUMEN
Hodgkin lymphoma (HL) is a rare lymphoid neoplasm in which Hodgkin/Reed-Stenberg (HRS) cells are admixed with a population of non-neoplastic inflammatory cells and fibrosis. Dysregulated expressions of cell cycle regulators and transcription factors have been proven as one of the hallmarks of HL. In that context, SATB1 and p16 have been reported as potential regulators of HL progression and survival. However, to date, no studies have assessed the expression levels of SATB1 and p16 in HL in Croatian patients or their prognostic values. Therefore, we investigated the expression pattern of SATB1 and p16 in paraffin-embedded lymph node biopsies using standard immunohistochemistry. We found that 21% of the patients stained positive for SATB1, while 15% of the patients displayed positive staining for p16. Furthermore, we aimed to understand the prognostic value of each protein through the analysis of the overall survival (OS) and progression-free survival (PFS). SATB1 showed a significantly positive correlation with better OS and PFS, while p16 expression had no impact. Interestingly, when patients were stratified by a combination of the two studied markers, we found that patients in the SATB1+/p16- group tended to have the best prognosis in HL, according to statistical significance. In conclusion, SATB1 and p16 might be potentially useful as diagnostic and prognostic markers for HL.
Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina , Enfermedad de Hodgkin , Proteínas de Unión a la Región de Fijación a la Matriz , Humanos , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/diagnóstico , Masculino , Femenino , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Adulto , Pronóstico , Persona de Mediana Edad , Croacia , Anciano , Adulto Joven , Adolescente , Biomarcadores de Tumor/metabolismoRESUMEN
Immune cells express an incredible variety of proteins; by measuring combinations of these, cell types influencing disease can be precisely identified. We developed terraFlow, a platform that defines cell subsets exhaustively by combinatorial protein expression. Using high-parameter checkpoint-focused and function-focused panels, we studied classical Hodgkin's lymphoma (cHL), where systemic T cells have not been investigated in detail. terraFlow revealed immune perturbations in patients, including elevated activated, exhausted, and interleukin (IL)-17+ phenotypes, along with diminished early, interferon (IFN)γ+, and tumor necrosis factor (TNF)+ T cells before treatment; many perturbations remained after treatment. terraFlow identified more disease-associated differences than other tools, often with better predictive power, and included a non-gating approach, eliminating time-consuming and subjective manual thresholds. It also reports a method to identify the smallest set of markers distinguishing study groups. Our results provide mechanistic support for past reports of immune deficiency in cHL and demonstrate the value of terraFlow in immunotherapy and biomarker studies.
Asunto(s)
Citocinas , Enfermedad de Hodgkin , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/metabolismo , Humanos , Citocinas/metabolismo , Masculino , Linfocitos T/inmunología , Linfocitos T/metabolismo , Femenino , Adulto , Persona de Mediana Edad , Interferón gamma/metabolismo , Agotamiento de Células TRESUMEN
Patients with advanced-stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG-PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression-free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification. We report on A-AVD escalation treatment outcomes for 15 iPET-positive patients post-ABVD. Overall response and complete response rates were 80% and 60%, respectively. Four patients underwent salvage therapy followed by autologous stem cell transplantation. At a median 17-month follow-up, all patients are alive, 87% in complete remission, and 1-year PFS was 57.8%. For patients ineligible for BEACOPP due to age, comorbidities, or preference, A-AVD escalation may be a viable alternative.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Brentuximab Vedotina , Dacarbazina , Doxorrubicina , Enfermedad de Hodgkin , Tomografía de Emisión de Positrones , Vinblastina , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Brentuximab Vedotina/uso terapéutico , Masculino , Femenino , Adulto , Bleomicina/administración & dosificación , Bleomicina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Vinblastina/uso terapéutico , Vinblastina/administración & dosificación , Dacarbazina/uso terapéutico , Dacarbazina/administración & dosificación , Adulto Joven , Estadificación de Neoplasias , Anciano , Resultado del Tratamiento , Estudios de SeguimientoRESUMEN
BACKGROUND: Classical Hodgkin lymphoma (CHL) is characterized by a proliferation of malignant cells of the lymphoreticular system and often involves lymph nodes, spleen, liver, and bone marrow; it is rare in the head and neck region. CASE DESCRIPTION: A 58-year-old man had an enlargement with ulceration in the left palatine tonsil that was causing dysphagia. Microscopic examination revealed an infiltrate of large, atypical lymphoid cells positive for cluster of differentiation 30, cluster of differentiation 15, PAX5, and Epstein-Barr virus. Complementary tests initially ruled out other sites of the disease. The results led to diagnosis of a rare development of CHL in the palatine tonsil, which was staged as IIEB. Before therapy was initiated, nodal lesions developed in the neck and the CHL was restaged as IIB. The patient was treated successfully with a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine. After a review of the literature, the authors found only 3 cases with the clinical, imaging, and microscopic features of primary CHL of the palatine tonsil. PRACTICAL IMPLICATIONS: Despite being a rare event, CHL may first develop in extranodal sites, such as the palatine tonsil. In this context, the role of the dentist is pivotal for early diagnosis of the disease. Investigations into the development of primary tonsillar CHL in the oropharynx are needed because the disease has a different clinical course than nodal lesions.
Asunto(s)
Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/diagnóstico , Masculino , Persona de Mediana Edad , Neoplasias Tonsilares/patología , Neoplasias Tonsilares/diagnóstico , Tonsila Palatina/patología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/diagnósticoRESUMEN
We present a series of 9 follicular lymphomas that progressed/transformed into classical Hodgkin lymphoma (CHL). Three cases of CHL showed a syncytial pattern (SCHL) making the differential diagnosis to Gray zone lymphoma (GZL) challenging. None of these three cases presented in the mediastinum. Based in all molecular data analyzed (BCL2/BCL6 FISH studies, IgH PCR and TNGS with a customized gene panel) we did find clonal relationship between the BCL2-positive FL cases and their CHL components in all cases. The three SCHL/GZL cases showed an activated phenotype according to Hans algorithm, presented the t(14; 18)(q32; q21), two out of three showed B cell markers and all expressed CD30 and p53. Interestingly, we identified three BCL2-negative FL cases with a further diagnosis of CHL expanding the spectrum of these association. In one of these three cases a different mutational profile was found in both the FL and the CHL components. All this data together suggests that CHL associated to BCL2-positive FL could be originated in a common progenitor cell (CPC) that give rise to both FL and CHL, acquiring this last component further genetic events in a linear fashion. On the other hand, no clonal relationship between CHL and BCL2-negative FL could be found, suggesting a fortuity association. Nevertheless, ample series of cases studied with more sensitive techniques are needed to confirm our hypothesis.
Asunto(s)
Biomarcadores de Tumor , Enfermedad de Hodgkin , Linfoma Folicular , Proteínas Proto-Oncogénicas c-bcl-2 , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Linfoma Folicular/patología , Linfoma Folicular/genética , Linfoma Folicular/diagnóstico , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Hibridación Fluorescente in Situ , Diagnóstico Diferencial , Mutación , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Ewing sarcoma is a malignant round-cell tumor that primarily affects bones in children. It can also arise in extraosseous tissues, such as the lung, kidneys, and liver. The presentation symptoms of Ewing sarcoma may include cough, dyspnea, and chest pain. CASE PRESENTATION: This report details the history of a 15-year-old Syrian boy with a previous diagnosis of Hodgkin lymphoma who presented with chronic shoulder pain. Imaging studies revealed an 80 mm mass in the apex of the left lung, which was confirmed through histopathological examination to be Ewing sarcoma following a computed-tomography-guided biopsy. The patient received multiple cycles of chemotherapy and subsequently underwent surgical resection of the remaining mass. CONCLUSIONS: This case highlights the rare occurrence of Ewing sarcoma in the lung and the unusual clinical presentation of shoulder pain without other accompanying symptoms.
Asunto(s)
Neoplasias Pulmonares , Sarcoma de Ewing , Tomografía Computarizada por Rayos X , Humanos , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/patología , Sarcoma de Ewing/diagnóstico por imagen , Masculino , Adolescente , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico por imagen , Dolor de Hombro/etiología , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/patología , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/patologíaRESUMEN
INTRODUCTION: The current treatment regimens for Hodgkin's lymphoma (HL) are associated with high incidences of adverse events. PURPOSE: This study aimed to compare the efficacy and safety of doxorubicin + bleomycin + vincristine + dacarbazine (ABVD) and standard bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (BEACOPP) chemotherapy in the treatment of advanced stage HL. METHODS: This multicenter, randomized, parallel, open, positive control noninferiority trial was conducted from 2016 to 2019 and comprised 93 subjects who were randomized in a 1:1 ratio between the treatment (BEACOPP; n = 44) and control (ABVD; n = 49) groups. RESULTS: The primary efficacy endpoint of this trial was the objective response rate (ORR) after eight cycles of chemotherapy, which was 100.00% (36/36) in the treatment group and 95.74% (45/49) in the control group. The incidence of adverse reactions was 100% in both groups. Significant differences (P < 0.05) in the incidences of grade 3 (39/44 [88.64%] vs. 23/49 [46.94%]) and grade 4 (27/44 [61.36%] vs. 8/49 [16.94%]) adverse events were observed between the treatment and control groups, respectively. However, most of these reactions were manageable, with no serious consequences, and were reversible after discontinuation of the treatment. CONCLUSION: Both regimens had a similar ORR and were associated with a high number of adverse events. The ABVD regimen was better tolerated and safer than the standard BEACOPP regimen. This study indicates that the standard BEACOPP regimen may be considered as a treatment option for patients with advanced HL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Ciclofosfamida , Dacarbazina , Doxorrubicina , Etopósido , Enfermedad de Hodgkin , Prednisona , Procarbazina , Vincristina , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Bleomicina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Vincristina/efectos adversos , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Masculino , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Procarbazina/uso terapéutico , Adulto , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Femenino , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/uso terapéutico , Dacarbazina/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/uso terapéutico , Persona de Mediana Edad , Adulto Joven , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Adolescente , Estadificación de Neoplasias , Resultado del TratamientoAsunto(s)
Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Finlandia/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Adolescente , Anciano , Adulto Joven , Anciano de 80 o más Años , Tasa de Supervivencia , NiñoRESUMEN
The Hodgkin and Reed - Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is thought to play a role in reducing antitumor responses. Here, we perform qualitative and quantitative analyses of lymphocytic and MDSC subtypes and determine the CD137 cell distribution in cHL primary tumors using multiplex immunofluorescence and automated multispectral imaging. The results were correlated with patients' clinical features. Cells were stained with specific panels of immune checkpoint markers (PD-1, PD-L1, CD137), tumor-infiltrating T lymphocytes (CD3, PD-1), and monocytic cells/MDSCs (CD68, CD14, CD33, Arg-1, CD11b). This approach allowed us to identify distinct phenotypes and to analyze spatial interactions between immune subpopulations and tumor cells. The results confirm CD137 expression by T, monocytic and HRS cells. In addition, the expression of CD137, T exhausted cells, and monocytic MDSCs (m-MDSCs) in the vicinity of malignant HRS cells were associated with a worse prognosis. Our findings reveal new elements of the TME that mediate immune escape, and confirm CD137 as a candidate target for immunotherapy in cHL.
CD137-expressing immune cells and HRS cells are more abundant and in closer proximity in refractory patients than in responders.Monocytic myeloid-derived suppressor cells (m-MDSCs) are associated with unfavorable outcomes and relapse in cHL, unlike granulocytic MDSCs (g-MDSCs), which are located far from HRS cells in non-responders.The cHL tumor microenvironment promotes immune escape in refractory patients by holistically driving polarization and/or recruitment of several cell types with increased expression of CD137 and PD-L1 checkpoints.
Asunto(s)
Enfermedad de Hodgkin , Células Supresoras de Origen Mieloide , Células de Reed-Sternberg , Microambiente Tumoral , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral , Humanos , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/metabolismo , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Microambiente Tumoral/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/patología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Células de Reed-Sternberg/patología , Células de Reed-Sternberg/metabolismo , Anciano , Análisis Espacial , Adulto Joven , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Adolescente , Pronóstico , Biomarcadores de Tumor/metabolismoRESUMEN
Classical Hodgkin lymphoma (cHL) is a common B-cell cancer and a significant health concern, especially in Western and Asian countries. Despite the effectiveness of chemotherapy, many relapse cases are being reported, highlighting the need for improved treatments. This study aimed to address this issue by discovering biomarkers through the analysis of gene expression data specific to cHL. Additionally, potential anticancer inhibitors were explored to target the discovered biomarkers. This study proceeded by retrieving microarray gene expression data from cHL patients, which was then analyzed to identify significant differentially expressed genes (DEGs). Functional and network annotation of the upregulated genes revealed the active involvement of matrix metallopeptidase 12 (MMP12) and C-C motif metallopeptidase ligand 22 (CCL22) genes in the progression of cHL. Additionally, the mentioned genes were found to be actively involved in cancer-related pathways, i.e., oxidative phosphorylation, complement pathway, myc_targets_v1 pathway, TNFA signaling via NFKB, etc., and showed strong associations with other genes known to promote cancer progression. MMP12, topping the list with a logFC value of +6.6378, was selected for inhibition using docking and simulation strategies. The known anticancer compounds were docked into the active site of the MMP12 molecular structure, revealing significant binding scores of -7.7 kcal/mol and -7.6 kcal/mol for BDC_24037121 and BDC_27854277, respectively. Simulation studies of the docked complexes further supported the effective binding of the ligands, yielding MMGBSA and MMPBSA scores of -78.08 kcal/mol and -82.05 kcal/mol for MMP12-BDC_24037121 and -48.79 kcal/mol and -49.67 kcal/mol for MMP12-BDC_27854277, respectively. Our findings highlight the active role of MMP12 in the progression of cHL, with known compounds effectively inhibiting its function and potentially halting the advancement of cHL. Further exploration of downregulated genes is warranted, as associated genes may play a role in cHL. Additionally, CCL22 should be considered for further investigation due to its significant role in the progression of cHL.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica , Simulación del Acoplamiento Molecular , Transcriptoma , Antineoplásicos/farmacología , Antineoplásicos/química , Metaloproteinasa 12 de la Matriz/genética , Metaloproteinasa 12 de la Matriz/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Terapia Molecular DirigidaAsunto(s)
Enfermedad de Hodgkin , Linfoma de Células B de la Zona Marginal , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/patología , Humanos , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/patología , Transformación Celular Neoplásica , MasculinoRESUMEN
ABSTRACT: Hodgkin lymphoma (HL) involving the central nervous system (CNS) is exceedingly rare. Information regarding the presentation, management, treatment, and outcome of patients with CNS HL is limited to case reports or small series. We describe 45 pediatric patients with 55 extra-axial CNS lesions at diagnosis with HL from a cohort of 4995 patients enrolled on Children's Oncology Group AHOD1331 and the European Network for Pediatric Hodgkin lymphoma C1 and C2 trials, with an overall incidence of 0.9%. Up to 82.2% of patients had a single CNS lesion in the thoracic, lumbar, or sacral spine. In the evaluated cohort, HL did not occur within the CNS parenchyma. Lesions extended into the extra-axial CNS space from adjacent soft tissue or bone and never directly infiltrated through the dura into the brain or spinal cord. Patients with CNS involvement had a twofold greater incidence of extranodal lesions than previously reported cohorts without CNS involvement. After 2 cycles of chemotherapy, 89.1% of CNS lesions demonstrated a complete metabolic response and >75% decrease in volume. Thirteen CNS lesions (23.6%) received irradiation; none were sites of disease relapse. Relapse occurred at the site of 2 lesions involving the CNS, both of which had an adequate interim response to chemotherapy. In summary, we present, to our knowledge, the largest reported cohort of systemic HL involving the CNS at diagnosis, demonstrating that these lesions originate from surrounding tissues, extend into the extra-axial CNS space, and respond similarly to other nodal and extranodal disease. The trials were registered at www.clinicaltrials.gov as #NCT02166463, #NCT00433459, and #NCT02684708.
Asunto(s)
Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/patología , Masculino , Adolescente , Femenino , Niño , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias del Sistema Nervioso Central/patología , Preescolar , Resultado del TratamientoRESUMEN
PURPOSE: Classic Hodgkin lymphoma (cHL) is a B-cell lymphoma that occurs primarily in young adults and, less frequently, in elderly individuals. A hallmark of cHL is the exceptional scarcity (1%-5%) of the malignant Hodgkin Reed-Sternberg (HRS) cells within a network of nonmalignant immune cells. Molecular determinants governing the relationship between HRS cells and their proximal microenvironment remain largely unknown. EXPERIMENTAL DESIGN: We performed spatially resolved multiplexed protein imaging and transcriptomic sequencing to characterize HRS cell states, cellular neighborhoods, and gene expression signatures of 23.6 million cells from 36 newly diagnosed Epstein-Barr virus (EBV)-positive and EBV-negative cHL tumors. RESULTS: We show that MHC-I expression on HRS cells is associated with immune-inflamed neighborhoods containing CD8+ T cells, MHC-II+ macrophages, and immune checkpoint expression (i.e., PD1 and VISTA). We identified spatial clustering of HRS cells, consistent with the syncytial variant of cHL, and its association with T-cell-excluded neighborhoods in a subset of EBV-negative tumors. Finally, a subset of both EBV-positive and EBV-negative tumors contained regulatory T-cell-high neighborhoods harboring HRS cells with augmented proliferative capacity. CONCLUSIONS: Our study links HRS cell properties with distinct immunophenotypes and potential immune escape mechanisms in cHL.
Asunto(s)
Enfermedad de Hodgkin , Células de Reed-Sternberg , Microambiente Tumoral , Humanos , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/virología , Células de Reed-Sternberg/patología , Microambiente Tumoral/inmunología , Herpesvirus Humano 4/aislamiento & purificación , Femenino , Masculino , Perfilación de la Expresión Génica , Adulto , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Persona de Mediana Edad , Linfocitos T CD8-positivos/inmunología , Anciano , TranscriptomaRESUMEN
Hodgkin lymphoma (HL) represents a neoplasm primarily affecting adolescents and young adults, necessitating the development of precise diagnostic and monitoring tools. Specifically, classical Hodgkin lymphoma (cHL), comprising 90% of cases, necessitating tailored treatments to minimize late toxicities. Although positron emission tomography/computed tomography (PET/CT) has enhanced response assessment, its limitations underscore the urgency for more reliable progression predictive tools. Genomic characterisation of rare Hodgkin Reed-Sternberg (HRS) cells is challenging but essential. Recent studies employ single-cell molecular analyses, mass cytometry, and Next-Generation Sequencing (NGS) to unveil mutational landscapes. The integration of liquid biopsies, particularly circulating tumor DNA (ctDNA), extracellular vesicles (EVs), miRNAs and cytokines, emerge as groundbreaking approaches. Recent studies demonstrate ctDNA's potential in assessing therapy responses and predicting relapses in HL. Despite cHL-specific ctDNA applications being relatively unexplored, studies emphasize its value in monitoring treatment outcomes. Overall, this review underscores the imperative role of liquid biopsies in advancing HL diagnosis and monitoring.
Asunto(s)
Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/patología , Biopsia Líquida/métodos , ADN Tumoral Circulante/genética , Biomarcadores de TumorRESUMEN
OBJECTIVE: Twenty percent of all classical Hodgkin lymphoma (CHL) cases relapse and recur, especially in advanced stages with a high International Prognostic Score (IPS). Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a regulatory molecule that can inhibit the immune response and is related to tumor aggressiveness. This study aimed to determine the relationship between CTLA-4 expression in advanced-stage CHL and IPS, identifying it as a potential therapy target. RESULTS: In advanced-stage CHL, the group with a high IPS exhibited significantly higher mean CTLA-4 expression compared to the group with a low IPS (p = 0.003).The group with Hb level < 10.5 g/dl, leukocyte count > 15,000/µL, lymphocyte count < 8%, albumin level < 4 g/dl, and stage 4 exhibited higher CTLA-4 expression than the other group, although only leukocyte count and stage showed statistical significance (p = 0.004 and p = 0.020). Mean CTLA-4 expression was 239.84 ± 76.36 for nodular sclerosis, 293.95 ± 147.94 for mixed cellularity, 271.4 ± 23.56 for lymphocyte depleted, and 225.2 for lymphocyte-rich subtypes. The results suggest that CTLA-4 expression is associated with adverse prognostic factors in the IPS for advanced-stage CHL, supporting the notion that immune checkpoints play a role in cancer progression.
Asunto(s)
Antígeno CTLA-4 , Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/genética , Antígeno CTLA-4/metabolismo , Antígeno CTLA-4/genética , Masculino , Femenino , Pronóstico , Adulto , Persona de Mediana Edad , Adulto Joven , Adolescente , Estadificación de Neoplasias , Anciano , Biomarcadores de Tumor/metabolismoRESUMEN
Paraneoplastic glomerular disease (PGD) develops from tumor cell products, leading to renal dysfunction. Unlike direct tumor effects, PGD illustrates the complex association between cancer and diverse clinical presentations and outcomes. Initially detected in a Hodgkin's disease patient, current research has defined diagnostic criteria based on PGD symptoms and cancer progression. PGDs, although rare (found in <1% of adult cancer patients with overt renal manifestations), are crucial, as they can signal cancer onset and frequently resist standard glomerulonephritis treatments. The emerging field of onconephrology studies this relationship between kidney disorders and cancers. The exact cause of many PGD cases remains unknown. This review examines PGDs, their clinicopathological features, related cancers, and mechanisms, emphasizing the need for early diagnosis and tailored treatment for kidney disease and linked cancer.
Asunto(s)
Glomerulonefritis , Síndromes Paraneoplásicos , Humanos , Síndromes Paraneoplásicos/diagnóstico , Glomerulonefritis/diagnóstico , Glomerulonefritis/patología , Glomerulonefritis/terapia , Glomérulos Renales/patología , Glomérulos Renales/fisiopatología , Neoplasias/complicaciones , Neoplasias/diagnóstico , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/patologíaRESUMEN
PURPOSE OF REVIEW: Hodgkin lymphoma (HL) occurs at two age peaks around 25 and 60âyears of age. Due to varying fitness and co-morbidities older patients are a heterogeneous group that has relatively poor treatment outcomes. The evolving therapeutic landscape for older HL is summarized herein. RECENT FINDINGS: Due to lack of data from larger trials and approval of novel drugs, first-line treatment of limited-stage HL (i.e. early-stage favourable and unfavourable) remains largely A(B)VD and radiotherapy based. For patients with advanced-stage HL, the anti-CD30 antibody-drug conjugate brentuximab vedotin is approved in combination with AVD chemotherapy (BV-AVD). Due to toxicities such as febrile neutropenia or polyneuropathy and lack of improvement in progression-free and overall survival in the older subgroup, fully concomitant BV-AVD is however not used widely. More recently, promising early data was reported with the combination of nivolumab and AVD (N-AVD) in patients >60âyears with advanced-stage HL. Second-line treatment depends on fitness and might include high-dose chemotherapy and autologous stem-cell transplantation for selected patients. For unfit or multiply relapsed patients, anti-PD1 antibodies are the preferred treatment option. SUMMARY: The increasing number of older HL patients constitutes a therapeutic challenge despite recent advances and the increased usage of targeted agents.