A proposal for a new staging system for extranodal natural killer T-cell lymphoma: a multicenter study from China and Asia Lymphoma Study Group.
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ABSTRACT:
SUBMITTER: Hong H
PROVIDER: S-EPMC7387308 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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A proposal for a new staging system for extranodal natural killer T-cell lymphoma: a multicenter study from China and Asia Lymphoma Study Group.
Hong Huangming H Li Yexiong Y Lim Soon Thye ST Liang Chaoyong C Huang He H Yi Pingyong P Wu Tao T Du Xin X Zhang Mingzhi M Wang Jinghua J Zhu Jun J Liu Ting T Meng Fanyi F Wu Gang G Guo Ye Y Zhu Yuan Y Zhao Weili W Jin Jie J Li Juan J Deng Yanming Y Gu Kangsheng K Wu Xiangyuan X Ke Xiaoyan X Xie Derong D Lin Daren D Peng Zhigang Z Wu Junxin J Liu Qing Q Kim Won Seog WS Lin Tongyu T
Leukemia 20200217 8
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Project description:Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p < 0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.
| S-EPMC9291061 | biostudies-literature
Project description:BackgroundExtranodal natural killer T-cell lymphoma (NKTCL), nasal type, is a rare and aggressive malignancy that occurs predominantly in Asian and Latin American populations. Although Epstein-Barr virus infection is a known risk factor, other risk factors and the pathogenesis of NKTCL are not well understood. We aimed to identify common genetic variants affecting individual risk of NKTCL.MethodsWe did a genome-wide association study of 189 patients with extranodal NKTCL, nasal type (WHO classification criteria; cases) and 957 controls from Guangdong province, southern China. We validated our findings in four independent case-control series, including 75 cases from Guangdong province and 296 controls from Hong Kong, 65 cases and 983 controls from Guangdong province, 125 cases and 1110 controls from Beijing (northern China), and 60 cases and 2476 controls from Singapore. We used imputation and conditional logistic regression analyses to fine-map the associations. We also did a meta-analysis of the replication series and of the entire dataset.FindingsAssociations exceeding the genome-wide significance threshold (p<5 × 10(-8)) were seen at 51 single-nucleotide polymorphisms (SNPs) mapping to the class II MHC region on chromosome 6, with rs9277378 (located in HLA-DPB1) having the strongest association with NKTCL susceptibility (p=4·21 × 10(-19), odds ratio [OR] 1·84 [95% CI 1·61-2·11] in meta-analysis of entire dataset). Imputation-based fine-mapping across the class II MHC region suggests that four aminoacid residues (Gly84-Gly85-Pro86-Met87) in near-complete linkage disequilibrium at the edge of the peptide-binding groove of HLA-DPB1 could account for most of the association between the rs9277378*A risk allele and NKTCL susceptibility (OR 2·38, p value for haplotype 2·32 × 10(-14)). This association is distinct from MHC associations with Epstein-Barr virus infection.InterpretationTo our knowledge, this is the first time that a genetic variant conferring an NKTCL risk is noted at genome-wide significance. This finding underlines the importance of HLA-DP antigen presentation in the pathogenesis of NKTCL.FundingTop-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education (20110171120099), Program for New Century Excellent Talents in University (NCET-11-0529), National Medical Research Council of Singapore (TCR12DEC005), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the US National Institutes of Health (1R01AR062886, 5U01GM092691-04, and 1R01AR063759-01A1).
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| S-EPMC10685657 | biostudies-literature
Project description:Natural killer/T-cell (NK/T) lymphomas represent a group of rare tumors of NK and NK-T cells. The World Health Organization classifies NK-cell tumors into three types, extranodal NK/T-cell lymphomas (ENKL, nasal and non-nasal), NK-cell leukemias, and a blastic variant (CD4-positive, CD56-positive hematodermic neoplasms). We focus our review to the current concepts in biology and treatment of ENKL. Though considerable advances have been made in our understanding of NK-cell biology, malignant transformation including the role of Epstein-Barr virus, and prognosis, the rare nature of ENKL and its heterogeneity limit the ability to standardize therapy. Radiotherapy is fundamental to treatment of early-stage disease with a role for chemoradiotherapy among high-risk patients. The clinical course of advanced disease is highly aggressive with frequent chemotherapy resistance and a poor prognosis. Therapeutic approaches to advanced-stage or relapsed and refractory disease, including the appropriate sequence of chemotherapy, combined modality therapy, and stem cell transplantation is not well-established. International and multicenter clinical trials are needed for this rare and aggressive disease.
| S-EPMC5568825 | biostudies-other
Project description:Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NNKTL) has very unique epidemiological, etiologic, histologic, and clinical characteristics. It is commonly observed in Eastern Asia, but quite rare in the United States and Europe. The progressive necrotic lesions mainly in the nasal cavity, poor prognosis caused by rapid local progression with distant metastases, and angiocentric and polymorphous lymphoreticular infiltrates are the main clinical and histologic features. Phenotypic and genotypic studies revealed that the lymphoma is originated from either NK- or γδ T-cell, both of which express CD56. In 1990, the authors first reported the presence of Epstein-Barr virus (EBV)-DNA and EBV-oncogenic proteins, and EBV has now been recognized to play an etiological role in NNKTL. in vitro studies revealed that a wide variety of cytokines, chemokines, and micro RNAs, which may be produced by EBV-oncogenic proteins in the lymphoma cells, play important roles for tumor progression in NNKTL, and could be therapeutic targets. In addition, it was revealed that the interaction between NNKTL cells and immune cells such as monocytes and macrophages in NNKTL tissues contribute to lymphoma progression. For diagnosis, monitoring the clinical course and predicting prognosis, the measurements of EBV-DNAs and EBV-micro RNAs in sera are very useful. For treatment with early stage, novel concomitant chemoradiotherapy such as DeVIC regimen with local radiotherapy and MPVIC-P regimen using intra-arterial infusion developed with concomitant radiotherapy and the prognosis became noticeably better. However, the prognosis of patients with advanced stage was still poor. Establishment of novel treatments such as the usage of immune checkpoint inhibitor or peptide vaccine with molecular targeting therapy will be necessary. This review addresses recent advances in the molecular understanding of NNKTL to establish novel treatments, in addition to the epidemiologic, clinical, pathological, and EBV features.
| S-EPMC6476925 | biostudies-literature
Project description:BackgroundCombination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL).MethodsForty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m(2) on days 1-3; methotrextate 30 mg/m(2) on days 3 and 10; etoposide 100 mg/m(2) on days 1-3; and prednisolone 60 mg/m(2) per day on days 1-5) followed by involved field radiotherapy (IFRT).ResultsOverall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively.ConclusionDue to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL.
| S-EPMC4221378 | biostudies-literature
Project description:Background: Chemotherapy and radiotherapy are critical for treating early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL); however, the optimal therapy sequence remains unclear. Therefore, we performed this study to compare the efficacy of L-asparaginase/pegaspargase-based sequential versus sandwich chemoradiotherapy for patients newly diagnosed with stage IE-IIE ENKTL. Methods: Patients were categorized into sequential (N = 111) and sandwich (N = 104) groups. Chemotherapy regimens included GELOX, SMILE, and VLP. The median radiotherapy dose was 55.0 Gy (range, 40.0-63.0 Gy). Adverse events, treatment responses, and survival outcomes were analyzed. Results: Patients' clinical characteristics were largely comparable between the 2 groups; however, the sandwich group comprised a larger number of Ann Arbor stage IIE patients. Local invasion was the most significant predictor of overall survival (OS); local invasion and Ann Arbor stage were significant predictors of progression-free survival (PFS). There were no significant differences in the complete response rate (85.6% vs. 89.4%, p = 0.396), 3-year OS (77.5% vs. 80.8%, p = 0.636), or 3-year PFS rates (74.8% vs. 76.9%, p = 0.806) in the sequential vs. sandwich groups, respectively. The incidence of grade 3/4 hematological toxicities was higher in the sandwich group than in the sequential group (27.9% vs. 15.3%, respectively, p = 0.025). The response rates and survival outcomes in stage IE and IIE patients did not differ between sequential and sandwich groups. Conclusions: In the era of L-asparaginase/pegaspargase, both sequential and sandwich chemoradiotherapy are safe and similarly effective in patients with newly diagnosed stage IE-IIE ENKTL.
| S-EPMC5950589 | biostudies-literature
Project description:Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare subtype of lymphoma that is often associated with poor clinical prognosis. Several studies have shown that hepatitis B virus (HBV) infection may be associated with increased risk of B-cell non-Hodgkin lymphoma; however, because of the rarity of ENKTL, little is known about its association with HBV. Our study aimed to assess whether HBV infection was associated with increased odds of ENKTL. We conducted a hospital-based case-control study including 417 ENKTL cases and 488 age- and sex-matched subjects with nonmalignant diseases unrelated to HBV infection. Multivariable unconditional logistic regression analyses were performed to estimate adjusted odds ratios [AOR] and their corresponding 95% confidence intervals (CI). The results of the multivariable analysis showed that after adjustment for a set of known risk factors, patients previously infected with HBV (HBsAg-seronegative/anti-HBc-seropositive) and naturally immune to HBV (anti-HBs-seropositive/anti-HBc-seropositive) were at significantly greater odds of being diagnosed with ENKTL (AOR, 1.497; 95% CI 1.098-2.042, P=0.033 and AOR, 1.871; 95% CI 1.302-2.689, P=0.001, respectively). After adjusting for other factors, significantly greater odds of being diagnosed with ENKTL were observed among cases who reported ever drinking alcohol (AOR, 1.675; 95% CI 1.054-2.660, P=0.029). The odds of ENKTL diagnosis were not significantly associated with ABO blood type, cigarette smoking status or family history of cancer. The results of our study suggest that patients previously infected with HBV and naturally immune to HBV were at greater odds of being diagnosed with ENKTL.
| S-EPMC5604198 | biostudies-literature
Project description:PurposeRelapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) is a rare and aggressive type of non-Hodgkin lymphoma with limited treatment options. This phase II study evaluated the efficacy and safety of sugemalimab, an anti-PD-L1 monoclonal antibody, in R/R ENKTL.MethodsEligible patients received sugemalimab 1,200 mg intravenously once every 3 weeks for up to 24 months or until progression, death, or study withdrawal. The primary end point was objective response rate (ORR) assessed by an independent radiologic review committee. Key secondary end points included ORR assessed by the investigators, complete response rate, duration of response, and safety.ResultsAt the data cutoff (February 23, 2022), 80 patients were enrolled and followed for a median of 18.7 months. At baseline, 54 (67.5%) had stage IV disease and 39 (48.8%) had received ≥2 lines of prior systemic therapy. Independent radiologic review committee-assessed ORR was 44.9% (95% CI, 33.6 to 56.6); 28 (35.9%) patients achieved a complete response and seven (9.0%) achieved a partial response, with a 12-month duration of response rate of 82.5% (95% CI, 62.0 to 92.6). Investigator-assessed ORR was 45.6% (95% CI, 34.3 to 57.2), and 24 (30.4%) patients achieved a complete response. Most treatment-emergent adverse events were grade 1-2 in severity, and grade ≥ 3 events were reported in 32 (40.0%) patients.ConclusionSugemalimab showed robust and durable antitumor activity in R/R ENKTL. Treatment was well tolerated with expected safety profile for this drug class.
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