First-line non-anthracycline-based chemotherapy for extranodal nasal-type NK/T-cell lymphoma: a retrospective analysis from the CLCG.
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SUBMITTER: Qi SN
PROVIDER: S-EPMC7362384 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Extranodal natural killer/T cell lymphoma-nasal type (EN-NK/T-NT) is extremely rare in Western countries; however, it is the most common subtype of peripheral T cell lymphoma in China. Despite this, there are a limited number of clinicopathological research studies on Epstein-Barr virus (EBV)-negative EN-NK/T-NTs. EBV-negative EN-NK/T-NT is a rare disease type, which has not been fully investigated. If other diagnostic criteria are met, such as the lesions being located predominantly in the upper aerodigestive tract, the presence of angiocentricity or angioinvasion, necrosis and expression of NK/T-cell phenotype, EN-NK/T-NT may be diagnosed, even if EBV is negative. In the present study, 99 cases of EN-NK/T-NTs were analyzed retrospectively, among which seven cases were EBV-negative EN-NK/T-NTs and selected for further investigation. In addition, the present study reviewed previously published research into EN-NK/T-NT, highlighting that EBV-negative EN-NK/T-NT is rare and that its geographical distribution is mainly in countries in Asia, Central America and South America. Patients with EBV-negative EN-NK/T-NT were all of Chinese ethnicity, with a median age of 32 years and primarily female. Furthermore, these patients shared similar clinicopathological characteristics (such as the tumor occurring mainly in the upper aerodigestive tract, the presence of vascular destruction, necrosis and cytotoxic phenotypes) to patients with EBV-positive EN-NK/T-NT. Immunohistochemistry and molecular analysis results indicated that tumor cells were primarily of NK or cytotoxic T origin; however, EBV-encoded small RNAs were not detected in any of these cases. Among the immunochemistry markers, T-bet was statistical significantly different between EBV-positive and -negative cases. Fluorescence in situ hybridization was also performed in two EBV-negative cases, including one case with a co-deletion of 6q21 and PR/SET domain 1 genes. There was only available follow-up data in 3/5 patients who survived for 37–113 months (median, 40 months). As EN-NK/T-NT can be diagnosed, even when EBV is negative, awareness of this subtype may prevent misdiagnosis or delayed diagnosis.
| S-EPMC7401002 | biostudies-literature
Project description:Natural killer/T cell lymphoma (NKTCL) most frequently affects the nasal cavity and upper aerodigestive tract (UAT) and is often mistaken for reactive disease processes, such as chronic rhinosinusitis (CRS). Recently, alterations of the nasal resident microbiota have been found in CRS. However, nasal microbial features in NKTCL have never been reported. This case-control study collected 46 NKTCL patients, 25 CRS patients and 24 matched healthy controls (HCs) to analyze nasal microbial profiles via 16S rRNA sequencing technology to improve our understanding of changes in the nasal microbiota in NKTCL. We found that alpha diversity was significantly decreased, while beta diversity was significantly increased in NKTCL compared with those in CRS and HCs. The genus Corynebacterium was significantly depleted in CRS and NKTCL versus that in HCs, while genus Staphylococcus was the most abundant in the NKTCL compared to that in the other two groups. The nasal microbial community was significantly different between UAT-NKTCL and non-UAT NKTCL patients. Importantly, based on a panel of taxa, excellent classification power with an AUC of 0.875 between UAT-NKTCL and CRS was achieved. Furthermore, the alpha diversity of the nasal microbiota was associated with several clinical covariates of NKTCL. Finally, PICRUSt analysis implicated an array of distinct functions in NKTCL that might be involved in the pathogenesis of the disease. In conclusion, the nasal microbial profile was unique in NKTCL. The nose-microbiota-UAT NKTCL axis represents a panel of promising biomarkers for clinical practice and contributes to revealing the potential pathogenesis of this malignancy.
| S-EPMC8461088 | biostudies-literature
Project description:IntroductionThere is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell - ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors.Patient concernsA 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010.Diagnosispositron emission tomography-computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014.InterventionsThe patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient's condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg.OutcomesPET-CT imaging showed his lesions obtained remission after 8 months post-treatment.ConclusionThus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched.
| S-EPMC7969288 | biostudies-literature
Project description:BackgroundNasal-type extranodal natural killer (NK)/T cell lymphoma (ENKTL) is a rare and aggressive type of lymphoma. The optimal chemotherapy regimen for ENKTL has not yet been established. In this study, we compared the LVDP (L-asparaginase, etoposide, dexamethasone, and cisplatin) and GLIDE (gemcitabine, L-asparaginase, ifosfamide, dexamethasone, and etoposide) chemotherapy regimens for the treatment of ENKTL.MethodsA total of 267 patients with newly diagnosed ENKTL were included in this retrospective study. Propensity score matching (PSM) was used to adjust for confounders between the LVDP and GLIDE groups. Treatment responses, survival outcomes, and toxicities between the two groups were compared before and after PSM.ResultsAt the end of therapy, the objective response rate (ORR) and complete response (CR) were 83.5% and 62.2%, respectively, for all patients. The ORR and CR were 85.5% and 62.2% for the LVDP group compared with 79.3% and 62.2% for the GLIDE group, respectively, and no differences between the two groups were found (ORR, p = 0.212; CR, p = 0.996). With a median 71 months follow-up, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 64.3% and 68.5%, respectively. The 5-year PFS and OS were 65.6% and 70.1% for the LVDP group compared with 61.6% and 64.6% for the GLIDE group, respectively (PFS, p = 0.478; OS, p = 0162). After PSM, no significant differences in short-term efficacy (ORR, p = 0.696; CR, p = 0.264) or long-term efficacy (PFS, p = 0.794; OS, p = 0.867) between the two groups were identified. However, treatment-related toxicities were milder in the LVDP group compared to the GLIDE group, even after adjusting for confounders via PSM.ConclusionIn conclusion, both LVDP and GLIDE regimens are effective for the treatment of ENKTL. However, the LVDP regimen is safer than the GLIDE regimen, with milder treatment-related toxicities. Therefore, the LVDP regimen could be a preferable option for patients with ENKTL.
| S-EPMC10166983 | biostudies-literature
Project description:Biopsies and cell lines of natural killer/T-cell lymphoma, nasal type (NKTCL) were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared with peripheral T-cell lymphoma, not otherwise specified, NKTCL had greater transcript levels for NK-cell and cytotoxic molecules, especially granzyme H. Compared with normal NKcells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, Epstein-Barr Virus-induced genes, and PDGFRA. Notably, platelet-derived growth factor receptor alpha and its phosphorylated form were confirmed at the protein level, and in vitro the MEC04 NKTCL cell line was sensitive to imatinib. Deregulation of the AKT, Janus kinase-signal transducers and activators of transcription, and nuclear factor-kappaB pathways was corroborated by nuclear expression of phosphorylated AKT, signal transducers and activators of transcription 3, and RelA in NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 [1q44], IL6R [1q21.3], CCL2 [17q12], TNFRSF21 [6p12.3]). Several features of NKTCL uncovered by this analysis suggest perturbation of angiogenic pathways. Integrative analysis also evidenced deregulation of the tumor suppressor HACE1 in the frequently deleted 6q21 region. This study highlights emerging oncogenic pathways in NKTCL and identifies novel diagnostic and therapeutic targets.
| S-EPMC2826234 | biostudies-literature
Project description:Extranodal NK-/T-cell lymphoma (ENKTCL) is a rare and highly aggressive malignancy with significant racial and geographic variations worldwide. In addition to the formerly "nasal-type" initial description, these lymphomas are predominantly extranodal in origin and typically cause vascular damage and tissue destruction, and although not fully understood, Epstein-Barr virus (EBV) has an important role in its pathogenesis. Initial assessment must include a hematopathology review of representative and viable tumor areas without necrosis for adequate immunohistochemistry studies, including EBV-encoded small RNA (EBER) in situ hybridization (ISH). Positron emission tomography with 18-fluorodeoxyglucose (18F-FDG-PET/CT) for accurate staging is essential, and most patients will have localized disease (IE/IIE) at diagnosis. Apart from other T-cell malignancies, the best treatment even for localized cases is combined modality therapy (chemotherapy plus radiotherapy) with non-anthracycline-based regimens. For advanced-stage disease, l-asparaginase-containing regimens have shown improved survival, but relapsed and refractory cases have very poor outcomes. Nowadays, even with a better understanding of pathogenic pathways, up-front therapy is completely based on chemotherapy and radiotherapy, and treatment-related mortality is not low. Future strategies targeting signaling pathways and immunotherapy are evolving, but we need to better identify those patients with dismal outcomes in a pre-emptive way. Given the rarity of the disease, international collaborations are urgently needed, and clinical trials are the way to change the future.
| S-EPMC10388588 | biostudies-literature
Project description:Extranodal NK/T-cell lymphoma nasal type (ENKL) is a rare type of non-Hodgkin lymphoma that more frequently occurs in East Asia and Latin America. Even though its molecular background has been discussed in the last few years, the current knowledge does not explain the disease pathogenesis in most cases of ENKL. Here, we performed multiple types of next-generation sequencing on 34 ENKL samples, including whole-exome sequencing (9 cancer tissues and 4 cancer cell lines), targeted sequencing (21 cancer tissues), and RNA sequencing (3 cancer tissues and 4 cancer cell lines). Mutations were found most frequently in 3 genes, STAT3, BCOR, and MLL2 (which were present in 9, 7, and 6 cancer samples, respectively), whereas there were only 2 cases of JAK3 mutation. In total, JAK/STAT pathway- and histone modification-related genes accounted for 55.9% and 38.2% of cancer samples, respectively, and their involvement in ENKL pathogenesis was also supported by gene expression analysis. In addition, we provided 177 genes upregulated only in cancer tissues, which appear to be linked with angiocentric and angiodestructive growth of ENKL. In this study, we propose several novel driver genes of ENKL, and show that these genes and their functional groups may be future therapeutic targets of this disease.
| S-EPMC4627344 | biostudies-literature
Project description:A 74-year-old woman developed bilateral uveitis with high Epstein-Barr virus (EBV) DNA load in the vitreous fluid without lymphoma cells. Four years after the onset, T2-weighted contrast-enhanced MRI revealed hyperintense lesions in the right occipital and parietal lobe. A biopsy resulted in the diagnosis of extranodal NK/T-cell lymphoma nasal type (ENKL). The repeat region of LMP1, an EBV gene, detected in the brain lesion was identical to that detected in the vitreous fluid. ENKL of the central nervous system is quite rare, and the pathogenesis has not been determined. The lymphoma in this case might have been closely associated with the EBV-positive uveitis.
| S-EPMC5498208 | biostudies-literature
Project description:BACKGROUND Extranodal NK/T-cell lymphoma (ENKTL) of the nasal type is highly invasive and relatively resistant to chemotherapy. This study aimed to assess the efficacy and safety of an extended chemotherapy regimen with increased dose intensity. MATERIAL AND METHODS This was a retrospective cohort study of 69 patients <60 years old with an ECOG score 0-2 treated for ENKTL at the Second Affiliated Hospital of Xi'an Jiaotong University between January 2004 and December 2013. The outcomes were compared between patients who received >8 courses of high-intensity chemotherapy (n=37) vs. 6-8 courses (n=18) and <6 courses (n=14) of conventional chemotherapy. Regimens included improved CHOP, CHOP-E, EPOCH, MAED, MMED, SMILE, and Hyper-CVAD with an increased dose intensity in the >8 courses group. RESULTS The mean follow-up was 52 months (8 to 82 months). Remission rate did not differ significantly when compared among the 3 groups after 3 courses of chemotherapy (83.8%, 77.8%, and 78.6%, respectively, overall P=0.834), but the 5-year overall survival (OS) differed significantly (63.5%, 45.1%, and 22.9%, respectively, overall P=0.030), as did progression-free survival (PFS) (59.1%, 36.0%, and 15.1%, respectively, overall P=0.020), disease-free survival (DFS) (54.1%, 35.5%, and 12.9%, respectively, overall P=0.022), and total relapse rate throughout follow-up (37.04%, 50.0%, and 88.89%, respectively, overall P=0.027). There were no differences in adverse effects among the 3 groups. CONCLUSIONS These results suggest improved OS, PFS, DFS, and relapse rate in young patients with ENKTL receiving >8 courses of high-intensity chemotherapy.
| S-EPMC5117239 | biostudies-literature
Project description:Background: Recently double-hit lymphoma or double protein expressor lymphoma has been identified as a distinct group of diffuse large B cell lymphoma with poor prognosis. However, the expression status, clinical and prognostic effect of combined overexpression of MYC and BCL2 in extranodal NK/T-cell lymphoma, nasal type (ENKTL) are not known. Materials and methods: Paraffin-embedded lymphoma samples from 53 patients with newly diagnosed ENKTL were studied using immunohistochemistry for MYC and BCL2, and fluorescent in situ hybridization (FISH) for MYC and BCL2 were done on 5 tissue sections with highest percentages of both MYC and BCL2 positive lymphoma cells. Results: The median percentage of MYC-positive lymphoma cells and BCL2-positive lymphoma cells were 20% (range, 5%-45%) and 70% (10%-95%), respectively. Using median scores as cutoffs, we assigned each patient an IHC double-hit score (DHS) that ranged from 0 to 2. Using this DHS, 15 patients (28.3%) had a DHS of 0, 24 patients (45.3%) had a DHS of 1, and the remaining 14 patients (26.4%) had a DHS of 2. FISH analysis was performed on 5 tissue sections with DHS of 2, and none of them had MYC or BCL2 rearrangement. The DHS was not associated with patients' age, gender, disease stage, LDH level, B symptoms, performance status, or local tumor invasiveness. However, patients with tumor localized in extranasal sites seemed to have higher expression of BCL2 and higher DHS than nasal lesions (p=0.014 and 0.042, respectively). In univariate survival analysis, either high expression of MYC or BCL2 was significantly correlated with inferior PFS and OS (p<0.05). According to the DHS, patients with ENKTL could be divided into three significantly different risk groups for PFS and OS (3-year PFS rate for DHS of 0, 1, and 2 was 60%, 41%, and 21%, respectively, p=0.008; 3-year OS rate for DHS of 0, 1, and 2 was 79%, 49%, and 33%, respectively, p=0.015). In multivariate survival analysis, it was found that DHS was an independent prognostic factor for both PFS and OS (p=0.006 and 0.011, respectively). Conclusions: Our study demonstrated that DHS can help identify patients with newly diagnosed ENKTL who are at a high risk for a poor clinical outcome, which needs to be validated in prospective clinical trials with patients treated uniformly.
| S-EPMC5381167 | biostudies-literature