Progress of Hematopoietic Stem Cell Transplantation and Radiotherapy in the Treatment of Extranodal NK/T Cell Lymphoma

Extranodal Natural Killer/T-cell lymphoma (ENKTL) is an extremely rare type of lymphoma which is highly lethal. It mainly affects the midline area unfolding as a necrotic granulomatous and extremely disfiguring lesion. There are two subtypes of (NKTL); the most common one is nasal which appears in the nasal cavity including the nasopharynx, oropharynx, parts of the aero digestive tract and Waldeyer's ring. While the other rarer subtype, appears in sites like the skin, testis, gastrointestinal tract, salivary glands and muscle. ENKTL is popular for the expression of multidrug resistance-associated P-glycoprotein, which not only plays the main role at exporting many antitumor agents outside tumor cells, but also makes the disease hard to treat. It is commonly associated with Epstein-Barr virus (EBV) infection and commonly occurs in Asian populations. However, there is no single unified consensus yet as to what is the standardized treatment for ENKTL. Radiotherapy alone treatment, has been considered as a first-line therapy for localized ENKTL, which later on was found to be insufficient for improving survival rates. Thus, the combination of chemotherapy and radiotherapy has been recommended as a therapeutic modality for localized ENKTL. Several combination modalities of radiotherapy and chemotherapy have been advised in clinical practice including concurrent, sequential and sandwich chemo radiotherapy. For the best treatment outcome, only patients with localized nasal ENKTL and low risk of treatment failure are eligible for radiotherapy. Both radiotherapy and hematopoietic stem cell transplantation (HSCT) have been used as treatment modalities in ENKTL patients. Upfront HSCT was performed for ENKTL, but it was associated with a very poor prognosis even for the limited-stage disease. The evidence supporting the use of HSCT to treat ENKTL was derived from the results of a series of phase 1 and 2 trials along with retrospective studies. The end result was a unified consensus that consolidative HSCT is not necessary in patients with newly diagnosed localized ENKTL who achieved complete response after treatment with any of the modern chemo radiotherapy regimens. Hence, HSCT is solely advised for advanced and relapsed NKTL. The main debate remains over which HSCT is the most suitable for patients with newly diagnosed advanced NKTL and relapsed NKTL.

Automated summary

Extranodal Natural Killer/T-cell lymphoma (ENKTL) is an extremely rare and highly lethal type of lymphoma. It mainly manifests as necrotic granulomatous lesions in the midline area. There are two subtypes of ENKTL, with the nasal subtype being the most common and the other subtype affecting rarer sites. ENKTL is known for its expression of multidrug resistance-associated P-glycoprotein, making it difficult to treat. Radiotherapy combined with chemotherapy is recommended for localized ENKTL, while hematopoietic stem cell transplantation (HSCT) may be considered for advanced and relapsed cases.