Extranodal NK/T-cell lymphoma (ENKTL)

Diagnosis starts with a biopsy, a small piece of tissue taken from the nose or another affected area. This lymphoma grows into and damages blood vessels, so much of the tissue can be dead (necrosis). The sample needs living tumor cells, and more than one biopsy is often needed.

A pathologist, a doctor who diagnoses disease from tissue, tests the sample for markers such as CD3 and CD56. A test called EBER in situ hybridization looks for Epstein-Barr virus (EBV) inside the tumor cells. EBV is found in the tumor cells in nearly all cases, so this test is a key part of the diagnosis.

Next, doctors check how far it has spread (staging). A PET-CT scan is the main staging scan. It finds lymphoma in the skin and bone marrow better than older tests. A blood test measures the amount of EBV DNA in the blood (plasma EBV DNA). The level before treatment helps estimate risk. Repeat tests during treatment help show how well it is working.

Radiotherapy is an important part of localized nasal treatment, often combined with chemotherapy. Asparaginase-containing regimens are central to systemic treatment because ordinary anthracycline-based lymphoma regimens may work poorly in this disease.

Relapsed or refractory disease may be treated with additional asparaginase-based combinations, checkpoint inhibitors or clinical trials, depending on prior treatment and availability.

Allogeneic transplantation can be considered for selected eligible patients with advanced, high-risk or relapsed disease, including in early treatment planning. U.S. transplant guidelines (ASBMT, now ASTCT, 2017) recommend an own-cell (autologous) transplant to follow first treatment only when the disease is widespread. They also recommend one for lymphoma that comes back but still responds to treatment. When the disease is in one area, radiation is an essential part of treatment. Published transplant evidence is mainly nonrandomized, so disease stage and response must qualify broad recommendations.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

Outlook depends a great deal on how far the lymphoma has spread when it is found. Disease that stays in the nose area does better than disease that has spread or that started outside the nose. Age, general health, the LDH blood level and the amount of EBV DNA in the blood also matter. Doctors combine several of these in risk scores, such as PINK-E.

Results have improved since doctors began using asparaginase-based chemotherapy together with radiation. U.S. registry data also show better survival in more recent years. When the lymphoma comes back or does not respond, medicines that block PD-1 or PD-L1 (immune checkpoint inhibitors) help some people. A donor stem cell transplant can also give lasting control to some.

In a study of 135 adults who had a donor transplant in Europe and Asia from 2010 to 2020, 55.6% were alive 3 years later. People whose lymphoma had shrunk with treatment before transplant tended to stay free of it longer. These numbers describe groups of people treated in the past. They cannot tell any one person what will happen.