1. Epidemiology and basic concepts There are significant geographic differences in the incidence of NK/T-cell lymphoma (NKTCL), which is most common in Asian countries and accounts for 33% of peripheral T-cell lymphomas (PTCLs) according to the latest statistics in China, while in European and North American countries, NKTCL accounts for only 5% of PTCLs and is mainly seen in Asians, Mexicans and other immigrants from Central and South America. The reasons for the geographical differences and ethnic susceptibility are unclear and are generally thought to be related to EBV infection, but the exact pathogenesis is unknown. This type of lymphoma, which has distinct Asian characteristics and is more common in China, still has poor therapeutic efficacy, and many questions remain to be answered in clinical practice. NKTCL has an extranodal lymph node origin as its main manifestation. The most common site of disease is the upper respiratory tract (including the nasal cavity, nasopharynx, paranasal sinuses, and palate), and the nasal cavity is often the earliest and most predominant site of invasion, hence the name nasal NK/T-cell lymphoma. The disease also frequently invades sites outside the nasal cavity, including the skin, soft tissues, gastrointestinal tract, testes, lungs, eyes, brain, adrenal glands, breast, and tongue. In some intermediate to advanced cases, the adjacent or distant lymph nodes are often invaded. The WHO lymphatic system classification system refers to this disease as “NK/T-cell lymphoma, nasal type”. Multidrug resistance is the main culprit of poor treatment outcome: non-anthracycline regimens will become mainstream For a long time, CHOP regimens have been the standard chemotherapy regimen for aggressive lymphoma, but the efficacy for NK/T-cell lymphoma is poor. Prospective studies have found that induction therapy with CHOP and CHOP-like regimens resulted in tumor remission in only 60% of patients with limited stage disease; even the use of dose dense CHOP-14 or the more intense EPOCH regimens have not been shown to increase efficacy. chemotherapy, resulting in a median survival time of 1.6 years for patients with nasal NKTCL and only 0.36 years for nasal NKTCL. Much evidence suggests that multidrug resistance may be responsible for the failure of anthracycline-containing regimens. It was found that about 2/3 of patients with NK/T-cell lymphoma had overexpression of the multidrug resistance protein P-gp, and these patients had lower tumor remission rates and 2-year survival rates than those with low P-gp expression. Japanese scholars have achieved more satisfactory efficacy with the SMILE regimen containing levomucoidase for NKTCL, and some other phase II clinical studies with DICE and COPL regimens have also achieved better efficacy. In addition, gemcitabine, oxaliplatin, doxorubicin liposomes, IL-2, anti-angiogenic agents, and histone deacetylase inhibitors are also being tried for the treatment of NKTCL. Treatment of limited-stage NK/T-cell lymphoma: both radiotherapy and chemotherapy are important Approximately 80% of NKTCL has limited-stage disease (stage I/II) at the time of initial diagnosis, so it has been controversial whether treatment should be given first with chemotherapy as in other types of aggressive lymphoma or with radiotherapy as in squamous carcinoma of the head and neck. Current evidence suggests that radiotherapy is an essential treatment and its efficacy is closely related to the extent of irradiation (which should include the healthy nasal cavity, nasopharynx and paranasal sinuses) and the dose (45-45Gy). Previous studies have shown that combining chemotherapy with radiotherapy does not increase the efficacy and that patients who receive radiotherapy first have a better survival rate. However, these studies were non-randomized retrospective studies and had a significant selection bias because patients who received direct radiotherapy often had no B symptoms along with limited lesions. With advances in radiotherapy techniques, including 3D conformal radiotherapy, local recurrence is no longer the primary mode of treatment failure in limited-stage NKTCL, and more patients are dying due to systemic tumor dissemination.NKTCL as a systemic disease, giving effective induction chemotherapy before local treatment will potentially reduce the incidence of future distant metastases and will help reduce tumor load and alleviate systemic symptoms, thus allowing subsequent radiotherapy to proceed smoothly. Of course, the selection of an appropriate induction chemotherapy regimen appears to be crucial, as the tumor remission rate after induction chemotherapy is related to the prognosis, and the treatment failure rate of those patients who are not sensitive to chemotherapy after receiving radiotherapy remains high. 4. The role of high-dose chemotherapy combined with stem cell transplantation remains to be clarified Kwong conducted a review and analysis of the published relevant literature and showed that patients who obtained CR prior to transplantation had a better outcome when they received high-dose chemotherapy combined with autologous stem cell transplantation, but the prognosis of this group of patients was not poor even without transplantation. The outcome of patients with advanced or relapsed refractory disease who received autologous transplantation was not satisfactory, while the 2-year OS of allogeneic transplant recipients was about 40%. Autologous transplantation has the potential to be a therapeutic strategy to improve the cure rate of NKTCL, but it is currently believed that patients with early, CR-acquired NKTCL do not benefit from autologous stem cell transplantation, and whether patients with poor prognosis will benefit requires further validation.