Clinical Outcomes and Prognostic Factors of Front-Line Autologous Stem Cell Transplantation in Patients with Extranodal NK/T-Cell Lymphoma
Authors: Yhim Ho-Young , Kim Jin Seok , Mun Yeung-Chul , Seong Chu-Myong , Moon Joon Ho , Park Yong , Jo Jae-Cheol , Kim Seok Jin , Kwak Jae-Yong , Lee Je-Jung , Yang Deok-Hwan 
Published: October 2019

Abstract
Introduction
Extranodal NK/T cell lymphoma (ENKTL) is a rare and aggressive lymphoma subtype, but standard front-line therapy has not been established. The clinical outcome of patients (pts) with ENKTL after the treatment of conventional chemotherapy, especially pts with advanced stage, was generally poor. Therefore, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) as a consolidation could be one of promising strategies to improve the outcome of ENKTL. However, there have been few studies reporting the survival outcome or prognostic significances of front-line ASCT in pts with ENKTL. Thus, the aim of this study was to investigate the outcome of pts with ENKTL who had undergone front-line ASCT.
Patients and methods
We consecutively enrolled pts with ENKTL who achieved CR or PR after primary chemotherapy ± radiotherapy and underwent front-line ASCT from 8 institutions from Jan 2005 to Dec 2013. Pts who were performed ASCT for salvage setting after relapse were excluded. Pts were classified as limited or advanced diseases according to Ann Arbor stage, and NK/T cell prognostic index (NKPI), which included the presence of B symptom, stage III or IV, elevated serum lactate dehydrogenase (LDH) level, and regional lymph node involvement, were determined for prognosis. Treatment response was assessed according to the International Working Group response criteria. The progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method.
Results
A total of 56 pts (39 male, 17 female) with median age of 47 years (range, 18-64) was included in this analysis. Twenty-seven pts (52%) were advanced disease and 18 (32%) had B symptoms at diagnosis. ECOG performance was ≥ 2 in 7 (13%) and serum LDH level was elevated in 25 (45%). Thus, 36 pts (64%) were classified as high risk (≥ 2 factors) by the NKPI. Pts with advanced disease were associated with worse performance status, higher risk of NKPI, and more frequent extra-upper aerodigestive (EUA) origin than those with limited disease.
All pts received systemic chemotherapy including non-anthracycline-based (n=45, 80%) or CHOP/CHOP-like regimens (n=11, 20%). Involved field radiotherapy or chemoradiotherapy was given to 24 (83%) of pts with limited disease. The median time from diagnosis to ASCT was 6.7 months (range, 3.2-10.3), and pretransplant disease status consisted of 37 pts (66%) with complete response (CR) and 19 pts (34%) with partial response (PR). Only one treatment-related death (2%, fungal pneumonia) occurred following ASCT. With a median follow-up of 46.5 months (range, 3.7-109.5), 4-year PFS and OS were 50.5% (95% CI, 43.1-57.9) and 54.6% (95% CI, 46.6-62.6), respectively. Pts with advanced disease had inferior 4-year PFS (39.4% vs 63.2%, P=0.006) and OS (24.3% vs 69.9%, P=0.009), compared to pts with limited disease. CR achievement at transplantation was significantly associated with better PFS (4-year, 65.2% vs 21.1%, P=0.001) and OS (4-year, 67.1% vs 32.7%, P=0.006) than those with PR. This result was consistently important in pts with advanced disease (4-year PFS, 66.7% vs 8.3%, P=0.007). Multivariable analyses were performed separately in 2 steps. In the first step, analysis included all pts (N=56) and demonstrated that high risk of NKPI (HR, 3.10; 95% CI, 1.16-8.26), poor ECOG performance (HR, 3.84; 1.31-11.29), and PR at transplantation (HR, 4.22; 1.89-9.43) were independent predictors for worse PFS. In the second step, pts were stratified by stage. In the pts group with advanced stage (N=27), PR at transplantation (HR, 3.27; 1.07-10.04) and CHOP/CHOP-like primary chemotherapy (HR, 8.26; 1.59-43.05) were associated with higher risk of progression in multivariable analysis. In the pts group with limited stage (N=29), multivariable models revealed high risk of NKPI (HR, 4.22; 1.10-16.19) and EUA origin of anatomic subtype (HR, 10.02; 2.07-48.41) were independently associated with shortened PFS.
Conclusion
This is the largest study that specifically focused on the outcomes of front-line ASCT in pts with ENKTL. Our study represents that non-anthracycline-based chemotherapy followed by ASCT would be feasible and active treatment option for ENKTL. NKPI and pretransplant CR achievement were important factors for predicting clinical outcomes, particularly NKPI in limited disease and pretransplant response in advanced disease.

Disclosures
No relevant conflicts of interest to declare.