A clinicohaematological prognostic model for nasal-type natural killer/T-cell lymphoma: A multicenter study

Abstract

Extranodal NK/T-cell lymphoma, nasal type (NKTL) is an aggressive type of non-Hodgkin lymphoma closely associated with Epstein-Barr virus and characterized by varying degrees of systemic inflammation. We aim to examine the prognostic significance of peripheral blood neutrophil-lymphocyte ratio (NLR) in patients with NKTL. Therefore, we conducted a retrospective review of 178 patients with biopsy-proven NKTL from the National Cancer Centre Singapore and Samsung Medical Center, South Korea. Using receiver operating curve analysis, an optimal cut-off for high NLR (>3.5) in predicting overall survival (OS) was derived. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional regression. In patients with high NLR, estimated 5-year OS was 25% compared to 53% in those with low NLR. In multivariable analysis, high NLR, in addition to age ≥60 years, presence of B-symptoms and stage III/IV at diagnosis, was independently correlated with worse OS (HR 2.08; 95% CI 1.36 to 3.18; p = 0.0008) and progression-free survival (HR 1.66; 95% CI 1.11 to 2.46; p = 0.0128). A new prognostic index (NABS score) derived from these factors stratified patients into low (0), low-intermediate (1), high-intermediate (2) and high (3-4) risk subgroups, which were associated with 5-year OS of 76.5%, 55.7%, 29.2% and 0% respectively. In conclusion, high NLR is an independent prognostic marker and the NABS model can be used to risk-stratify NKTL patients.

Figure 1

Derivation of NLR. (a) An optimal cut-off for high NLR (>3.5) in predicting overall survival and progression-free survival was determined using receiver operating curve analyses. (b) A positive correlation was demonstrated between NLR and absolute neutrophil counts (Spearman’s rho 0.571, 95% CI 0.463 to 0.662, p <0.0001), (c) while a converse correlation with absolute lymphocyte counts was found (Spearman’s rho −0.591, 95% CI −0.679 to −0.486, p <0.0001).

Figure 2

Survival outcomes stratified by NLR. High NLR (>3.5) was associated with worse overall survival and progression-free survival in analysis of the entire cohort. In subgroup analysis, high NLR was consistently associated with worse overall survival both in the Singaporean and Korean cohorts.

Figure 3

Survival outcomes stratified by age, Ann-Arbor staging and presence of B symptoms. Older age at diagnosis (≥60 years old), advanced Ann-Arbor staging (stage III/IV) and presence of B symptoms was associated with worse overall survival and progression-free survival.

Figure 4

Overall and progression-free survival stratified by NABS score. Patients were risk-stratified based on their NABS score into low (0), low-intermediate (1), high-intermediate (2) and high (3–4) risk subgroups, which were associated with 5-year OS of 76.5%, 55.7%, 29.2% and 0%, and 2-year PFS of 64.8%, 59.5%, 37.1% and 9.4% respectively.

Figure 5

Gene set enrichment analysis (GSEA). Using the Hallmark gene set, upregulation of genes involved in DNA repair, unfolded protein response, mitotic spindle, and MTORC1 signaling were significantly enriched in cases with elevated NLR. The top 10 genes in each pathway are shown in the corresponding tables.