Allogeneic HSCT may improve survival in advanced extranodal NK/T-cell lymphoma: a single-center retrospective study

Abstract: Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is a rare and aggressive lymphoid malignancy highly associated with Epstein-Barr virus (EBV) infection. Patients with stage III or higher disease often have a poor prognosis. This study retrospectively reviewed the treatment courses of 34 patients with relapsed/refractory (R/R) ENKTCL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center between January 2019 and July 2024. The results showed that in this study, the use of programmed cell death protein 1 inhibitors before transplantation, the number of treatment lines, and whether the plasma EBV was negative or not had no significant impact on overall survival and progression-free survival. Patients achieving complete response or partial response before allo-HSCT exhibited a more favorable prognosis. Conversely, a history of chronic active EBV infection before transplantation and EBV reactivation after transplantation were associated with inferior survival, suggesting poor prognostic outcomes. Genetic susceptibility analysis revealed that patients with advanced ENKTCL frequently harbored hemophagocytic lymphohistiocytosis (HLH)–associated gene variants. LYST gene variants were the most commonly identified HLH-related alterations, and patients developing HLH experienced significantly higher nonrelapse mortality. Furthermore, TP53 gene variants were associated with post–allo-HSCT relapse. In conclusion, allo-HSCT may improve survival in selected patients with high-risk, advanced-stage R/R ENKTCL. These single-center, retrospective findings are hypothesis-generating and require validation in larger, multicenter studies with longer follow-up.