Autologous stem cell transplantation in NK/T-cell lymphoma: Prognostic impact of EBV-DNA in a multinational cohort-A study by the EBMT Lymphoma Working Party

Abstract

Natural killer (NK)/T-cell lymphomas (NKTCLs) are rare, aggressive lymphomas prevalent in East Asia and South America. Despite improvements, largely due to asparaginase-based therapies, outcomes for advanced disease remain poor, and the role of autologous stem cell transplantation (auto-HCT) remains controversial. This study evaluated real-world outcomes of auto-HCT in NKTCL patients across Asia and Europe. We included 130 adult NKTCL patients undergoing auto-HCT between 2011 and 2022 using data from the European Society for Blood and Marrow Transplantation (EBMT) registry and South Korean registry data. Median age was 51.3 years; 66.9% were male. Most patients (95.1%) had an Eastern Cooperative Oncology Group (ECOG) score 0-1; 65.3% had Stage III-IV disease. One prior therapy line was reported in 53.1%, and ≥2 lines in 46.9%. Asparaginase-based regimens were used in 79.5% pretransplant. Responses at auto-HCT included complete (59.7%), partial (27.9%) remission, and stable/progressive disease (12.4%). Epstein-Barr virus (EBV)-DNA in the peripheral blood was reported in 37.3%. With a median follow-up of 4.6 years, 3-year overall survival (OS) and progression-free survival (PFS) were 63.8% and 47.6%. Relapse and NRM rates at 3 years were 46.7% and 5.7%. Patients in complete remission had improved 3-year OS (75.2%) compared to PR (52.8%) and stable/progressive disease (32.0%) (P = 0.007). Detectable EBV-DNA in the blood at auto-HCT was associated with poor outcomes (3-year OS: 26.7% vs. 78.1% in patients with undetectable EBV-DNA; P < 0.0001). Patients achieving complete remission and undetectable EBV-DNA in the blood before auto-HCT had a favorable survival, suggesting auto-HCT may be a treatment option in selected high-risk patients. This is the largest multinational cohort evaluating prognostic factors for auto-HCT for NKTCL.

Figure 1

Patient flow and major outcomes of natural killer/T‐cell lymphoma (NKTCL) patients after autologous stem cell transplantation (auto‐HCT). Patient flow and key outcome parameters for NKTCL patients undergoing auto‐HCT. (A) Flow diagram for patterns of treatment and outcomes. Kaplan–Meier estimates for (B) overall survival (OS) and (C) progression‐free survival (PFS). Cumulative incidence curves for (D) relapse incidence (RI) and (E) non‐relapse mortality (NRM). Time‐to‐event data for PFS, RI, and NRM were available for 124 patients, as shown in panels (C)–(E). EBV, Epstein‐Barr virus.

Figure 2

Overall survival of natural killer/T‐cell lymphoma patients by region and disease factors. Kaplan–Meier estimates for overall survival of indicated subgroups. (A) Patients transplanted in European or Asian centers. (B) Limited disease stage (I/II) versus advanced disease stage (III/IV) at diagnosis. (C) Timing of autologous stem cell transplantation (auto‐HCT) as upfront treatment (after 1 treatment line) versus 2 or more treatment lines. (D) Remission status at autologous stem cell transplantation (auto‐HCT) shown as CR versus PR versus SD/PD. (E) Epstein–Barr virus (EBV)‐DNA not detectable versus detectable at auto‐HCT. (F) CR1 patients stratified by EBV‐DNA not detectable versus detectable at auto‐HCT. CR, complete remission; CR1, complete remission after 1 treatment line; PR, partial remission; SD/PD, stable disease/progressive disease.

Figure 3

Forest plots of multivariable analysis of prognostic factors for OS and PFS. The hazard ratios (HR) and corresponding 95% confidence intervals (95% CIs) were obtained from multivariable regression using the Cox proportional‐hazards model. These results pertain to the independent variables evaluated for predicting post‐autologous stem cell transplantation (auto‐HCT) outcomes in all natural killer/T‐cell lymphoma patients. CR, complete remission; EBV, Epstein‐Barr virus; OS, overall survival; PFS, progression‐free survival; PINK, prognostic index for NK/T‐cell lymphoma; PR, partial remission; Ref., reference group; SD/PD, stable disease/progressive disease.