Page 284 - Haematologica March 2020

M. Ando et al.
(3 of 3). Of these, two were refractory to initial therapy. They survived for only one month (2 of 3) and 4 months (1 of 3). The lymphoma cells of these three patients did not express LMP1. Statistical analysis showed that distinct PD-L1 expression of ENKL was significantly correlated with poor prognosis (P=0.001). Even in advanced-stage disease, PD-L1 expression was significantly associated with poor OS (P=0.031) (Figure 1E). Another factor confer- ring poor OS in ENKL was the lack of LMP1 expression
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(P=0.009) (Figure 1F). Treatment with SMILE was associ- ated with favorable OS in advanced-stage disease (P=0.008) (Figure 1G), whereas plasma EBV DNA positiv- ity did not significantly affect OS in these ENKL patients (P=0.181) possibly due to the small number of EBV-DNA negative group (Figure 1H). Table 2 shows the results of cross-tabulation analysis of the correlations between PD- L1 expression and variables including age, sex, clinical stage, EBV DNA titre, SMILE history, CR, and LMP1
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Figure 1. Representative immunohistochemical features, analy- sis of programmed death-ligand 1 expression in extranodal NK/T-cell lymphoma, nasal type (ENLK), and overall survival in patients with ENKL according to various factors. (A) PD-L1+ ENKL cells expressed PD-L1 (brown). (B) PD-L1+ nonmalignant cells were identified. ENKL cells did not express PD-L1. (C) PD-1+ TILs were not observed in most ENKL cases. (D) PD-1+ TILs (1%) were observed only in two ENKL cases. (E) Overall survival (OS) of patients among the two PD-L1 expressing groups (positive group vs weakly positive and negative groups) (the entire study cohort: left; advanced stage cohort: right). (F) OS of patients according to LMP1 positivity. (G) OS of patients in advanced stage who received dexamethasone, methotrexate, ifosfamide, L-asparagi- nase, and etoposide (SMILE) therapy. (H) OS of patients according to EBV DNA positivity. PD-L1: programmed death-ligand 1; TIL: tumor-infiltrating lymphocytes; PD-1: programmed cell death 1; LMP: latent membrane protein; EBV: Epstein-Barr virus.
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haematologica | 2020; 105(3)