Retrospective Analysis of NK/T Cell Lymphoma Prognostic Index (NKPI), EBV-DNA and Soluble IL-2 Receptor (sIL2R) for Extranodal NK/T-Cell Lymphoma, Nasal Type
Authors: Inoue Norihito , Nishimura Noriko , Takahashi Anna , Yamauchi Hirofumi , Kusano Yoshiharu , Ueda Kyoko , Mishima Yuko , Yokoyama Masahiro , Terui Yasuhito , Hatake Kiyohiko 
Published: October 2019

Abstract
Introduction
Extranodal NK/T cell lymphoma (ENKTL) is a rare aggressive lymphoma, and more prevalent in Asians, Mexico, Central America, and South America. ENKTL relates to Epstein-Barr Virus (EBV) reactivation, and occurs most often in adults.
The prognosis of ENKTL relates to NK/T Cell Lymphoma Prognostic Index (NKPI), which includes presence of B symptom, elevated serum lactate dehydrogenase (LDH), stageⅢ or Ⅳ, and regional lymph node involvement. Recently, EBV-DNA level is known to be an important prognosis factor of ENKTL.
We retrospectively analyzed relationship among NKPI, EBV-DNA level and other factors in patients with ENKTL.
Patients and methods
We analyzed the data of ENKTL patients who were diagnosed and treated at our hospital from April 2007 to July 2016, retrospectively. Data of the blood test and EBV-DNA level, when we diagnosed were also analyzed. PET-CT examination was performed for staging of ENKTL before treatment.
The event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier method.
Results
A total of 26 ENKTL patients (14 male, 12 female) were analyzed. All patients were treated with radiation therapy (RT) and 2/3DeVIC (dexamethasone 40mg/body days 1 through 3, ifosfamide 1000mg/m² days 1 through 3, carboplatin 200mg/m² day 1, etoposide 67mg/m² days 1 through 3).
Median age was 58 years old (range; 18-77 years old). Median OS was 17 months (range; 1-105 months), and EFS was 12 months (range 1-105 months).
Seven patients had B symptoms, and serum LDH level (median 192.5 U/L, range 153-540 U/L) was elevated in 10 patients at diagnosis. The patients with stage Ⅰ, Ⅱand Ⅳ were 19, 5, and 2 patients, respectively. The patients with stage Ⅳ were treated with RT and 2/3DeVIC, because patient's performance status, age or other factor is not good.
According to the NKPI, the patients were stratified into low score (10 patients), low intermediate (13 patients), and high intermediate (3 patients).
In our analysis, 2 year-EFS (p=0.125) was not changed among all score groups o However,, low score group was associated with better 2 year-OS (p=0.0734) than intermediate and high score groups.
Twenty patients were tested EBV-DNA level at diagnosis. Median EBV-DNA at diagnosis was 113.5 copies/10⁶WBC (range; 0-38000 copies/10⁶WBC). We analyzed relationship between the prognosis and EBV-DNA level. However, EBV-DNA level (EBV-DNA cut-off; 140 copies/10⁶WBC ) was not related to 2 year-OS (p=0.838) and 2 year-EFS (p=0.686).
Twenty-six patients were tested serumβ2-microglobulin (β2MG) and soluble IL-2 receptor (sIL2R). Serum β2MG level (median; 2.035 mg/l , range; 1.10-4.95 mg/l) was increased in 13 patients, and serum sIL2R level (median; 543 U/ml, range; 264-2490 U/ml) was increased in 14 patients.
β2MG level was not related to 2 year-OS (p=0.152) and 2 year-EFS (p=0.181). Low sIL2R level was associated with better OS (p=0.0445) and EFS (p=0.0793) than high level.
Discussion NKPI score and serum sIL2R were related to the prognosis of patients with ENKTL with early stage, although EBV-DNA copies were not related to the prognosis.

Disclosures
Nishimura: Chugai: Consultancy. Mishima:Chugai: Consultancy. Yokoyama:Chugai: Consultancy. Terui:Yanssen: Honoraria. Hatake:Chugai: Research Funding; Meiji-Seika: Consultancy; Otsuka: Consultancy; Kyowa Kirin: Honoraria, Research Funding.