Epstein-Barr Virus-Positive Natural Killer/T-Cell Lymphoma

Cai, Qingqing; Cai, Jun; Yu, Fang; Young, Ken H.

doi:10.3389/fonc.2019.00386

Cited by 30 publications

(56 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Natural killer/T-cell lymphoma (NKTL) is a well-characterized subtype of peripheral T-cell lymphoma that is more common in East Asia and Latin America. 1 , 2 More than two-thirds of NKTL patients have stage I or II diseases in the upper aerodigestive tract at the time of diagnosis. 3 , 4 The prognosis of this subgroup of patients has been significantly improved with the use of concurrent chemoradiotherapy or sequential chemoradiotherapy with non-anthracycline chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma

Cai

Huang

et al. 2020

Sig Transduct Target Ther

Self Cite

View full text Add to dashboard Cite

Advanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death 1 (PD-1) antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced NKTL. Nine patients underwent six 21-day cycles of anti-PD-1 antibody (day 1), pegaspargase 2000 U/m2 (day 1), gemcitabine 1 g/m2 (days 1 and 8) and oxaliplatin 130 mg/m2 (day 1), followed by anti-PD-1 antibody maintenance every 3 weeks. Programmed death-ligand 1 (PD-L1) expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing (NGS) analysis. Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) and computed tomography or magnetic resonance imaging. Eight patients exhibited significant responses, comprising of seven complete remissions and one partial remission (overall response rate: 88.9%). After a median follow-up of 10.6 months, 6/9 patients (66.7%) remained in complete remission. The most common grade 3/4 adverse events were anemia (33.3%), neutropenia (33.3%), and thrombocytopenia (33.3%); all of which were manageable and resolved. Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression (5/6, 83.3%). NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy. Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D, TET2, and BCORL1 might indicate a poor response to immunochemotherapy. In conclusion, the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL. PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma

Cai

Huang

et al. 2020

Sig Transduct Target Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…Extranodal natural killer/T‐cell lymphoma, nasal type (ENKL) is a rare, aggressive and distinct entity characterized by its association with Epstein‐Barr virus (EBV) 1,2 . ENKL can cause destruction in the involved site because of its highly invasive behavior, which greatly affects patients’ quality of life.…”

mentioning

confidence: 99%

DDGP vs. SMILE in Relapsed/Refractory Extranodal Natural Killer/T‐cell Lymphoma, Nasal Type: A Retrospective Study of 54 Patients

Wang

Meng

et al. 2020

Clinical Translational Sci

View full text Add to dashboard Cite

Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a rare peripheral T-cell lymphoma that predominantly occurs in Asian and South American populations. The treatment of ENKL has been a challenge for a long time. This study was conducted to compare the clinical efficacy and safety of cisplatin, dexamethasone, gemcitabine, and pegaspargase (DDGP) and methotrexate, dexamethasone, ifosfamide, L-asparaginase, and etoposide (SMILE) regimens for relapsed/refractory ENKL and explore the prognostic factors. From October 2014 to July 2019, 54 patients with relapsed/refractory ENKL who received DDGP or SMILE chemotherapy were retrospectively assessed in this study. Thirty-one patients received DDGP chemotherapy and 23 patients received SMILE chemotherapy. A higher complete response rate was observed in patients treated with DDGP regimen (61.3% vs. 30.4%, P = 0.025). The DDGP group (95% confidence interval (CI) of 5-year progression-free survival (PFS): 24.6-66.2%; 95% CI of 5-year overall survival (OS): 8.5-91.7%) was also significantly associated with longer 5-year PFS and 5-year OS (P = 0.008 for 5-year PFS, P = 0.023 for 5-year OS). More serious leucopenia (P = 0.021), neutropenia (P = 0.041), and allergy (P = 0.040) were observed in the SMILE group. Post-treatment Epstein-Barr virus (EBV)-DNA status (P = 0.001 for PFS, P = 0.018 for OS) was identified as a significant prognostic factor for PFS and OS in multivariate analysis. The present research suggested that compared with SMILE chemotherapy, DDGP chemotherapy can significantly improve the response and survival of relapsed/refractory ENKL with better tolerance. Post-treatment EBV-DNA status was identified as a significant prognostic factor for PFS and OS in relapsed/refractory ENKL. Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a rare, aggressive and distinct entity characterized by its association with Epstein-Barr virus (EBV). 1,2 ENKL can cause destruction in the involved site because of its highly invasive behavior, which greatly affects patients' quality of life. In addition, ~ 30-50% patients will relapse after initial treatment within 5 years, and the treatment of relapsed/refractory ENKL remains challenging. 3

show abstract

“…A pathogenetic role for Epstein Barr Virus (EBV), identified several years ago (4), was recently supported by data (5,6) regarding the severe forms of NK cell proliferation, i.e. Aggressive NK Cell Leukemia (ANKL) and Nasal NK/T-Cell Lymphoma (NKTCL).…”

Section: Introductionmentioning

confidence: 99%

Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?

et al. 2021

View full text Add to dashboard Cite

Large granular lymphocyte leukemias (LGLL) are sustained by proliferating cytotoxic T cells or NK cells, as happens in Chronic Lymphoproliferative Disorder of Natural Killer cells (CLPD-NK), whose etiology is only partly understood. Different hypotheses have been proposed on the original events triggering NK cell hyperactivation and transformation, including a role of viral agents. In this perspective, we revise the lines of evidence that suggested a pathogenetic role in LGLL of the exposure to retroviruses and that identified Epstein Barr Virus (EBV) in other NK cell leukemias and lymphomas and focus on the contrasting data about the importance of viral agents in CLPD-NK. EBV was detected in aggressive NK leukemias but not in the indolent CLPD-NK, where seroreactivity against HTLV-1 retrovirus envelope BA21 protein antigens has been reported in patients, although lacking clear evidence of HTLV infection. We next present original results of whole exome sequencing data analysis that failed to identify viral sequences in CLPD-NK. We recently demonstrated that proliferating NK cells of patients harbor several somatic lesions likely contributing to sustain NK cell proliferation. Thus, we explore whether “neoantigens” similar to the BA21 antigen could be generated by aberrancies present in the leukemic clone. In light of the literature and new data, we evaluated the intriguing hypothesis that NK cell activation can be caused by retroviral agents located outside the hematopoietic compartment and on the possible mechanisms involved with the prospects of immunotherapy-based approaches to limit the growth of NK cells in CLPD-NK disease.

show abstract

Epstein-Barr Virus-Positive Natural Killer/T-Cell Lymphoma

Cited by 30 publications

References 116 publications

Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma

Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma

DDGP vs. SMILE in Relapsed/Refractory Extranodal Natural Killer/T‐cell Lymphoma, Nasal Type: A Retrospective Study of 54 Patients

Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?

Contact Info

Product

Resources

About