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ABSTRACT: Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.
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Neoplasias do Sistema Nervoso Central , Humanos , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Linfoma de Células T/patologia , Linfoma de Células T/diagnóstico , Linfoma de Células T/mortalidade , Prognóstico , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/terapia , Fatores de Risco , Recidiva , Células Matadoras Naturais , Adulto JovemRESUMO
Introduction: Natural killer/T cell lymphoma (NKTL) is an aggressive malignancy associated with poor prognosis. This is largely due to limited treatment options, especially for relapsed patients. Immunotherapies like immune checkpoint inhibitors (ICI) and anti-CD38 therapies have shown promising but variable clinical efficacies. Combining these therapies has been suggested to enhance efficacy. Methods: We conducted a case study on a relapsed NKTL patient treated sequentially with anti-CD38 followed by ICI (anti-PD1) using cytometry analyses. Results and Discussion: Our analysis showed an expected depletion of peripheral CD38+ B cells following anti-CD38 treatment. Further analysis indicated that circulating anti-CD38 retained their function for up to 13 weeks post-administration. Anti-PD1 treatment triggered re-activation and upregulation of CD38 on the T cells. Consequently, these anti-PD1-activated T cells were depleted by residual circulating anti-CD38, rendering the ICI treatment ineffective. Finally, a meta-analysis confirmed this counterproductive effect, showing a reduced efficacy in patients undergoing combination therapy. In conclusion, our findings demonstrate that sequential anti-CD38 followed by anti-PD1 therapy leads to a counterproductive outcome in NKTL patients. This suggests that the treatment sequence is antithetic and warrants re-evaluation for optimizing cancer immunotherapy strategies.
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ADP-Ribosil Ciclase 1 , Inibidores de Checkpoint Imunológico , Humanos , ADP-Ribosil Ciclase 1/antagonistas & inibidores , ADP-Ribosil Ciclase 1/metabolismo , ADP-Ribosil Ciclase 1/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfoma Extranodal de Células T-NK/terapia , Linfoma Extranodal de Células T-NK/imunologia , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Glicoproteínas de Membrana/antagonistas & inibidores , Masculino , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Pessoa de Meia-Idade , Feminino , Resultado do TratamentoRESUMO
The molecular pathogenesis of extranodal NK/T-cell lymphoma (NKTCL) remains obscured despite the next-generation sequencing (NGS) studies explored on ever larger cohorts in the last decade. We addressed the highly variable mutation frequencies reported among previous studies with comprehensive amplicon coverage and enhanced sequencing depth to achieve higher genomic resolution for novel genetic discovery and comparative mutational profiling of the oncogenesis of NKTCL. Targeted exome sequencing was conducted to interrogate 415 cancer-related genes in a cohort of 36 patients with NKTCL, and a total of 548 single nucleotide variants (SNVs) and 600 Copy number variances (CNVs) were identified. Recurrent amplification of the MCL1 (67%) and PIM1 (56%) genes was detected in a dominant majority of patients in our cohort. Functional mapping of genetic aberrations revealed that an enrichment of mutations in the JAK-STAT signaling pathway, including the cytokine receptor LIFR (copy number loss) upstream of JAK3, STAT3 (activating SNVs), and downstream effectors of MYC, PIM1 and MCL1 (copy number gains). RNA in situ hybridization showed the significant consistence of MCL1 RNA level and copy number of MCL1 gene. We further correlated molecular and clinical parameters with overall survival (OS) of these patients. When correlations were analyzed by univariate followed by multivariate modelling, only copy number loss of LIFR gene and stage (III-IV) were independent prognostic factors of reduced OS. Our findings identified that novel loss of LIFR gene significantly correlated with the adverse clinical outcome of NKTCL patients and provided therapeutic opportunities for this disease through manipulating LIFR.
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Linfoma Extranodal de Células T-NK , Mutação , Humanos , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/terapia , Linfoma Extranodal de Células T-NK/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Prognóstico , Variações do Número de Cópias de DNAAssuntos
Linfoma Extranodal de Células T-NK , Humanos , Linfoma Extranodal de Células T-NK/terapia , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/patologia , Imunoterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.
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Linfoma Extranodal de Células T-NK , Humanos , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/terapia , Linfoma Extranodal de Células T-NK/diagnóstico , Genômica , Imunoterapia , Instabilidade Genômica , Células Matadoras Naturais/patologiaRESUMO
BACKGROUND: Ophthalmic lymphomas, a subgroup of extra-nodal lymphomas, have seen an increase in incidence in recent decades. Of these, the NK/T-cell lymphoma (NKTL) subtype is particularly aggressive. Though prevalent mostly in Asian patients, data on ophthalmic NKTL is still limited, especially in the western population. This study aimed to provide an additional analysis of primary ophthalmic NKTL using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A retrospective analysis was performed on the SEER database covering records from 2000 to 2020. Patients diagnosed with extranodal NKTL originating primarily from an ophthalmic structure were identified. RESULTS: Out of 4540 ophthalmic lymphomas registered in the SEER database between 2000 and 2020, 9 cases (0.2%) corresponded to ophthalmic NKTL, occurring in patients with a median age of 67 years. The majority of these patients underwent chemotherapy (88.8%) and radiotherapy (66.6%). The 6-month overall survival (OS) and cancer-specific survival (CSS) were both at 50.8%, dropping significantly at the 2-year follow-up. CONCLUSION: Primary orbital NKTL has a notably severe prognosis. An early diagnosis is important due to the aggressive nature of NKTL.
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Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Humanos , Idoso , Estudos Retrospectivos , Linfoma Extranodal de Células T-NK/epidemiologia , Linfoma Extranodal de Células T-NK/terapia , Linfoma Extranodal de Células T-NK/diagnóstico , Células Matadoras NaturaisRESUMO
Natural killer/T-cell lymphoma (NKTCL) is an aggressive and malignant condition with a high mortality rate. Prognostic factors may assist to evaluate the outcome of the disease and may also be useful in selecting appropriate therapeutic strategies for patients. The study aims to describe NKTCL in terms of its clinical features, laboratory examinations, and immunophenotypes and to analyze relevance affecting patient survival outcomes. The patients diagnosed as NKTCL in Jinling Hospital from Jan. 2012 to Dec. 2022 were reviewed retrospectively in this study basing on histopathology. The analysis was performed to evaluate overall survival (OS). A total of 125 NKTCL patients were included, which mainly affected male more than female with the onset median age of 51.00 years old (range, 14 ~ 85 y). NKTCL commonly affects the nasopharynx and upper aerodigestive tract, intestines, and skin. The median overall survival was 13.00 months (range, 2-156 m), and the 5-year survival rate was 9.8%. Under univariable analysis revealed the following factors at diagnosis age: serum total IgEAb ≥ 54.6 IU/mL, IL-6 ≥ 32.445 ng/L, elevated PINK score, smoking, and extranasopharyngeal site were statistically significant predictors for OS. Compared to the patients who received radiotherapy alone or chemotherapy alone, the patients who received combined chemoradiotherapy had longer OS. We found that IL-6 and total IgEAb were significant prognostic factors in NKTCL patients. Also, extranasopharyngeal site was correlated with advanced disease.
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Interleucina-6 , Linfoma Extranodal de Células T-NK , Humanos , Masculino , Feminino , Adolescente , Prognóstico , Estadiamento de Neoplasias , Estudos Retrospectivos , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/terapia , Linfoma Extranodal de Células T-NK/patologia , Células Matadoras Naturais/patologiaRESUMO
Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL), is characterized by Epstein-Barr virus infection and poor prognosis. We established a novel cell line, ENKL-J1, from bone marrow cells of an ENKL patient. We found that ENKL-J1 cells express the ganglioside GD2 (GD2) and that GD2-directed chimeric antigen receptor T cells exhibit cytotoxicity against ENKL-J1 cells, indicating that GD2 would be a suitable target of GD2-expressing ENKL cells. Targeted next-generation sequencing revealed TP53 and TET2 variants in ENKL-J1 cells. Furthermore, single-cell RNA sequencing in ENKL-J1 cells showed high gene-expression levels in the oncogenic signaling pathways JAK-STAT, NF-κB, and MAPK. Genes related to multidrug resistance (ABCC1), tumor suppression (ATG5, CRYBG1, FOXO3, TP53, MGA), anti-apoptosis (BCL2, BCL2L1), immune checkpoints (CD274, CD47), and epigenetic regulation (DDX3X, EZH2, HDAC2/3) also were expressed at high levels. The molecular targeting agents eprenetapopt, tazemetostat, and vorinostat efficiently induced apoptosis in ENKL-J1 cells in vitro. Furthermore, GD2-directed chimeric antigen receptor T cells showed cytotoxicity against ENKL-J1 cells in vivo. These findings not only contribute to understanding the molecular and genomic characteristics of ENKL; they also suggest new treatment options for patients with advanced or relapsed ENKL.
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Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Receptores de Antígenos Quiméricos , Humanos , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Epigênese Genética , Receptores de Antígenos Quiméricos/genética , Análise da Expressão Gênica de Célula Única , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/terapia , Linfoma Extranodal de Células T-NK/patologia , Linhagem CelularRESUMO
Interim 18F-FDG PET/CT (I-PET) has a role in response evaluation and treatment guidance in patients with nasal-type extranodal natural killer/T cell lymphoma (ENKTL). However, there was no agreement on the timing of I-PET performed, after chemotherapy or after chemoradiotherapy. We aimed to find the appropriate timing for I-PET by assessing the prognostic value of I-PET in response evaluation in ENKTL patients. Two hundred and twenty-seven ENKTL patients who had undergone I-PET were retrospectively included. All patients were grouped based on their therapeutic strategy received, chemotherapy or chemoradiotherapy. The Deauville 5-point score (DS) was used to interpret the I-PET images. The hazard ratio (HR) and C-index were used to measure the discriminatory and prognostic capacities of I-PET performed at different times. One hundred and six patients underwent the I-PET after chemotherapy (chemotherapy group), while I-PET was performed after chemoradiotherapy in 121 patients (chemoradiotherapy group). Eighty-seven patients were classified as metabolic remission (DS score of 1-3), while the other 140 were classified as non-metabolic remission (DS score of 4-5) according to the Deauville criteria. There were no significant survival differences between patients in metabolic remission and in non-metabolic remission in either progression-free survival (PFS, p = 0.406) or overall survival (OS, p = 0.350). In the chemotherapy group, patients in metabolic remission had significantly superior PFS than patients in non-metabolic remission (p = 0.012). For OS, a discriminative trend was also found on the survival curve between patients in metabolic remission and in non-metabolic remission (p = 0.082). In the chemoradiotherapy group, there was no significant difference in PFS (P = 0.185) or OS (P = 0.627) between patients in metabolic remission and in non-metabolic remission. I-PET after chemotherapy yields higher discriminative power and has the ability for prognostic prediction in nasal-type ENKTL patients. I-PET after radiochemotherapy has no prognostic value. Thus, the appropriate timing for I-PET is after chemotherapy but before radiotherapy for response evaluation in nasal-type ENKTL patients.
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Linfoma Extranodal de Células T-NK , Humanos , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Linfoma Extranodal de Células T-NK/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Estudos Retrospectivos , Prognóstico , Células Matadoras Naturais/patologiaRESUMO
While all peripheral T-cell lymphomas are uncommon, certain subtypes are truly rare, with less than a few hundred cases per year in the USA. There are often no dedicated clinical trials in these rare subtypes, and data are generally limited to case reports and retrospective case series. Therefore, clinical management is often based on this limited literature and extrapolation of data from the more common, nodal T-cell lymphomas in conjunction with personal experience. Nevertheless, thanks to tremendous pre-clinical efforts to understand these rare diseases, an increasing appreciation of the biological changes that underlie these entities is forming. In this review, we attempt to summarize the relevant literature regarding the initial management of certain rare subtypes, specifically subcutaneous panniculitis-like T-cell lymphoma, hepatosplenic T-cell lymphoma, intestinal T-cell lymphomas, and extranodal NK/T-cell lymphoma. While unequivocally established approaches in these diseases do not exist, we make cautious efforts to provide our approaches to clinical management when possible.
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Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Humanos , Linfócitos T/patologia , Estudos Retrospectivos , Células Matadoras Naturais/patologia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/patologia , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/terapiaRESUMO
Extranodal NK/T-cell lymphoma (ENKTL), nasal type and aggressive NK cell leukemia are rare in Western World been less than 1% in USA to 8% in Asia among Non-Hodgkin's lymphomas. It is aggressive, with poor outcome and optimal treatment is unclear. A combination therapy that includes Peg-Asparaginase (SMILE) has been employed in young patients. An 85-year-old Puerto Rican male presented with anorexia, epistaxis, vertigo and involuntary facial movements. He was treated with injectable Onabotulinum toxin A due to suspicion of a hemifacial spasm. However, a CT scan demonstrated a left maxillary sinus lesion extending into the left middle turbinate with biopsy consistent with ENKTL. We adjusted therapy to patient's age and performance receiving Gemcitabine-Oxaliplatin (Gemox) with radiation obtaining a complete response with persistent negative Epstein Barr DNA titers. ENKTL is a rare disease initially misdiagnosed in our elderly patient, who demonstrated adequate response with a modified therapeutic regime.
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Linfoma Extranodal de Células T-NK , Idoso de 80 Anos ou mais , Humanos , Masculino , Biópsia , Hispânico ou Latino , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/terapia , Oxaliplatina/uso terapêuticoRESUMO
BACKGROUND: Overexpressed EZH2 is oncogenically involved in the pathogenesis of different cancerous contexts including extranodal natural killer/T cell lymphoma (ENKTL). However, the underlying mechanisms of EZH2 upregulation have not been fully clarified and it is still difficult to target EZH2 in ENKTL. RESULTS: Current study identifies an E3 ligase TRIP12 that triggers K63-linked polyubiquitination of EZH2 in ENKTL and unexpectedly, stabilizes EZH2. As determined by gene expression profiling (GEP), TRIP12 and EZH2 levels correlate with each other in ENKTL patient samples. Aided by quantitative mass spectrometry (MS) and follow-up analysis, we identify K634 as the ubiquitination site of EZH2. Further study confirms that TRIP12-mediated EZH2 K634 ubiquitination enhances the interaction between EZH2 and SUZ12 or CDK1 and increases the level of EZH2 T487 phosphorylation. This study further demonstrates the TRIP12-EZH2 signaling might be regulated by cytoplasmic HSP60. Importantly, the TRIP12-EZH2 axis mediates ENKTL cell migration via accelerating epithelial-mesenchymal transition (EMT). Moreover, our study finds out dexamethasone treatment manipulates TRIP12-EZH2 signaling and may represent a novel therapeutic strategy against ENKTL metastasis. CONCLUSIONS: Altogether, TRIP12 induces K63-linked site-specific polyubiquitination of EZH2 for stabilization, which promotes ENKTL cell migration and could be targeted by dexamethasone treatment.
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Linfoma Extranodal de Células T-NK , Humanos , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/terapia , Metilação de DNA , Ubiquitinação , Células Matadoras Naturais , Dexametasona , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteínas de Transporte/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
The staging, prognostication, and treatment of ENKTL has evolved over the years with better understanding of the disease biology. There is significant heterogeneity in the treatment followed across the world. Literature from India have been few with small number of patients. We studied the outcomes and prognostic factors of patients with ENKTL treated between May 2010 and December 2021 at our center. A total of 78 patients diagnosed with ENKTL were treated at our center. L-asparaginase based chemotherapy was administered in 84% of the patients. Close to 2/3rd patients received SMILE chemotherapy. After a median follow-up of 30 months (18.5-41.4 months), the median relapse free survival and overall survival for the overall population was 45 months (12-118 months) and 45 months (14-118 months) respectively. By multivariate analysis, PINK score of 2-4, non-receipt of RT and non-achievement of CR were associated with poor survival.
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Linfoma Extranodal de Células T-NK , Humanos , Prognóstico , Linfoma Extranodal de Células T-NK/terapia , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Asparaginase/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND Nasal-type extranodal natural killer/T-cell lymphoma (ENKL) is an exceedingly rare and aggressive subtype of non-Hodgkin lymphoma. The malignancy has both a high morbidity and mortality and is most commonly discovered in patients with advanced stages of the disease. As a result, early detection and treatment is tantamount to improving survival and minimizing lasting effects. CASE REPORT Herein, we report a case of nasal-type ENKL in a woman with facial pain and associated nasal and eye discharge. We highlight the histopathologic features from nasopharyngeal and bone marrow biopsy, which demonstrated Epstein-Barr virus-positive biomarkers of diffuse and subtle involvement, respectively, with associated chromogenic immunohistochemical staining. We also highlight existing therapy utilizing a combination of chemotherapy with radiation, as well as consolidation therapy, and suggest the need for further research of allogeneic hematopoietic stem cell treatment and the potential of programmed death ligand 1 (PD-L1) inhibition in managing nasal-type ENKL malignancy. CONCLUSIONS Nasal-type ENKL is a rare subtype of non-Hodgkin lymphoma that is infrequently associated with bone marrow involvement. The malignancy has a poor prognosis overall and typically is discovered late in the disease course. Current treatment favors utilization of combined modality therapy. However, previous studies have been inconsistent in determining whether chemotherapy or radiation therapy can be used alone. Additionally, promising results have also been shown with chemokine modulators, including antagonistic drugs that target PD-L1, in refractory and advanced cases.
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Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Feminino , Humanos , Antígeno B7-H1 , Herpesvirus Humano 4 , Medula Óssea , Infecções por Vírus Epstein-Barr/complicações , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/terapia , Células Matadoras NaturaisRESUMO
BACKGROUND: Extranodal natural killer/ T-cell lymphoma (ENKTL) is a rare malignant tumor. This study aimed to develop a predictive nomogram and a web-based survival rate calculator for dynamically predicting the survival of patients with sinonasal ENKTL (SN-ENKTL). METHODS: This study investigated patients (n = 134) with SN-ENKTL who had been initially treated in our hospital between Jan 2008 and Dec 2016. The patients were randomly divided into training and validation cohorts, in a 7:3 ratio. Independent prognostic factors were identified and integrated to build a predictive nomogram and a web-based calculator using the Cox-regression model. The nomogram was evaluated by consistency index and calibration curve. RESULTS: Age, lactate dehydrogenase, hemoglobin, Epstein-Barr virus DNA, and Ann Arbor stage were identified as independent risk factors. We constructed a predictive nomogram for survival and a web-based calculator (https://taiqinwang.shinyapps.io/DynNomapp/). CONCLUSION: This study developed a prognostic model and a web-based calculator specifically focused on SN-ENKTL for otolaryngologists to use to facilitate timely treatment decisions for the disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1645-1651, 2023.
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Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Neoplasias dos Seios Paranasais , Humanos , Linfoma Extranodal de Células T-NK/terapia , Estudos Retrospectivos , Herpesvirus Humano 4 , Prognóstico , Células Matadoras Naturais/patologiaRESUMO
KEYPOINTS: Extranodal NK/T-cell lymphoma (ENKL) was the most common sinonasal lymphoma at our hospital. ENKL occurs at a younger age, and is more prevalent in the nasal cavity. ENKL had a lower Ann Arbor stage, and a better prognosis than diffuse large B-cell lymphoma (DLBLC).
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Linfoma Extranodal de Células T-NK , Linfoma Difuso de Grandes Células B , Neoplasias dos Seios Paranasais , Humanos , Prognóstico , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/terapia , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/epidemiologia , Neoplasias dos Seios Paranasais/terapia , Cavidade Nasal/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed. RESULTS: Combined with pathology, imaging, bone marrow examinationï¼ etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimenï¼gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5ï¼ was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later. CONCLUSION: PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.
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Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Humanos , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Etoposídeo , Recidiva Local de Neoplasia/tratamento farmacológico , Asparaginase , Desoxicitidina , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma Extranodal de Células T-NK/terapia , Oxaliplatina/uso terapêuticoRESUMO
Anti-SARS-CoV-2 vaccines were developed in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the BNT162b2 mRNA vaccine is effective, adverse effects have been reported. Here, we report a case of extranodal NK/T-cell lymphoma, nasal type (ENKL), of the left arm following BNT162b2 mRNA vaccination. A 73-year-old male presented with a lump in the left arm, which was the site where he received the BNT162b2 mRNA vaccine 3 months prior. He was treated with topical corticosteroids and debridement, but the tumor progressed. Additionally, fever, night sweats, and general fatigue were observed. Laboratory findings included thrombocytopenia, elevated lactate dehydrogenase, and soluble interleukin-2 receptor levels. Skin biopsy led to a diagnosis of ENKL. The patient was treated with a 50% dose of SMILE therapy and radiotherapy, resulting in regression of the tumor. It seems that latent Epstein-Barr virus (EBV)-infected NK/T cells were reactivated by vaccination and contributed to the onset of ENKL. This is the first report of ENKL after BNT162b2 mRNA vaccination. The present case highlights the possible risk of development of malignant lymphoma, including ENKL at the injection site, after BNT162b2 COVID-19 vaccination.
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COVID-19 , Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Masculino , Humanos , Idoso , Herpesvirus Humano 4/genética , Vacina BNT162 , Vacinas contra COVID-19/efeitos adversos , Braço/patologia , COVID-19/prevenção & controle , COVID-19/complicações , SARS-CoV-2 , Linfoma Extranodal de Células T-NK/terapiaRESUMO
Controlling nutritional status (CONUT) score as an original nutritional assessment tool can be used to assess the prognosis of patients with a variety of malignancies. However, the predictive power of CONUT in extranodal natural killer/T cell lymphoma (ENKTL) patients has never been demonstrated. Our retrospective multicenter study aimed to explore the prognostic value of CONUT in newly diagnosed ENKTL. A total of 1085 newly diagnosed ENKTL patients between 2003 and 2021 were retrospectively retrieved. Cox proportional hazard model was used to explore the prognostic factors of overall survival (OS). The survival rate of ENKTL was evaluated using Kaplan-Meier analysis, and log-rank test was applied to the difference between groups. We investigated the prognostic performance of CONUT, the International Prognostic Index (IPI), the Korean Prognostic Index (KPI), and the Prognostic Index of Natural Killer Cell Lymphoma (PINK) using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). The median age at diagnosis for the whole cohort was 47 years, and the male to female ratio was 2.2:1. The 5-year OS for all patients was 72.2%. Multivariable analysis showed that CONUT, age, bone marrow involvement, ECOG PS score, and Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL stage were identified as independent predictive factors for OS. Based on multivariable results, a prognostic nomogram was developed. Subgroup analysis demonstrated that patients with severe malnutrition had poorest clinical outcome. In addition, ROC curves and DCA analysis proved that compared with IPI, KPI, and PINK models, the CONUT score-based nomogram showed a better prognostic predictive efficiency of ENKTL. CONUT could effectively stratify the prognosis of ENKTL and the proposed nomogram based on CONUT was an effective prognostic model for prediction.
Assuntos
Linfoma Extranodal de Células T-NK , Nomogramas , Humanos , Masculino , Feminino , Prognóstico , Estado Nutricional , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/terapia , Estudos Retrospectivos , Células Matadoras Naturais/patologiaRESUMO
(A) Correlation matrix of unsupervised co-regulated genes, based on the 208 genes included in the NanoString platform. Some of the clusters of co-regulated genes corresponded to the following: Inflammatory cells; Epstein-Barr virus; B-cells; Cytotoxic T-cells; T-cells; and Proliferation. (B) Analysis of genomic alterations by targeted sequencing. Distribution of mutations in the 62 analyzed genes. Rows correspond to sequenced genes, columns represent individual patients. Color coding: green, missense; blue, synonymous; pink, frameshift; violet, Indel; red, stop gained; yellow, UTR.