How we treat NK/T-cell lymphomas

• Published in: Journal of hematology and oncology Vol. 15; no. 1; p. 74
• Main Authors: Tse, Eric, Zhao, Wei-Li, Xiong, Jie, Kwong, Yok-Lam
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03-06-2022; BioMed Central; BMC
• Subjects: Aggressive leukaemia/lymphoma; Anthracycline; Anthracyclines; Apoptosis; Asparaginase; Autografts; Bone marrow; Computed tomography; Cytotoxicity; Drug resistance in microorganisms; Epigenetics; Epstein-Barr virus; Gastrointestinal system; Gastrointestinal tract; Gene expression; Health aspects; Hematology; Hematopoietic stem cells; Histone deacetylase; Hybridization; Immunotherapy; Leukemia; Lymph nodes; Lymphocytes T; Lymphoma; Metabolism; Microenvironments; Monoclonal antibodies; Multidrug resistance; Mutation; Nasal; Natural killer cells; NK/T-cell lymphoma; Non-Hodgkin's lymphomas; Non-nasal; Oncology; Patients; PD-1 protein; PD-L1 protein; PET imaging; Phenotypes; Positron emission tomography; Proteins; Radiotherapy; Review; RNA; Signal transduction; Skin tests; Stem cell transplantation; T cells; T-cell lymphoma; Tomography; Transplantation; Tumors; Immune checkpoint; NK/T-cell lymphoma; Nasal; Non-nasal; Aggressive leukaemia/lymphoma; PD1; Radiotherapy; Asparaginase
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-022-01293-5

Natural killer (NK)/T-cell lymphomas are aggressive malignancies with a predilection for Asian and South American populations. Epstein-Barr virus (EBV) infection in lymphoma cells is universal. Predominantly extranodal, NK/T-cell lymphomas are divided clinically into nasal (involving the nose and upper aerodigestive tract), non-nasal (involving the skin, gastrointestinal tract, testes, and other organs), and aggressive leukaemia/lymphoma (involving the marrow and multiple organs) subtypes. Initial assessment should include imaging with positron emission tomography computed tomography (PET/CT), quantification of plasma EBV DNA as a surrogate marker of lymphoma load, and bone marrow examination with in situ hybridization for EBV-encoded small RNA. Prognostication can be based on presentation parameters (age, stage, lymph node involvement, clinical subtypes, and EBV DNA), which represent patient factors and lymphoma load; and dynamic parameters during treatment (serial plasma EBV DNA and interim/end-of-treatment PET/CT), which reflect response to therapy. Therapeutic goals are to achieve undetectable plasma EBV DNA and normal PET/CT (Deauville score ≤ 3). NK/T-cell lymphomas express the multidrug resistance phenotype, rendering anthracycline-containing regimens ineffective. Stage I/II nasal cases are treated with non-anthracycline asparaginase-based regimens plus sequential/concurrent radiotherapy. Stage III/IV nasal, and non-nasal and aggressive leukaemia/lymphoma cases are treated with asparaginase-containing regimens and consolidated by allogeneic haematopoietic stem cell transplantation (HSCT) in suitable patients. Autologous HSCT does not improve outcome. In relapsed/refractory cases, novel approaches comprise immune checkpoint blockade of PD1/PD-L1, EBV-specific cytotoxic T-cells, monoclonal antibodies, and histone deacetylase inhibitors. Future strategies may include inhibition of signalling pathways and driver mutations, and immunotherapy targeting the lymphoma and its microenvironment.