PTCLs and NKTCLs were more prevalent in Eastern Asia and the distribution of subtypes, prognosis and outcome were different from other ethnic populations. There were more ENKLs (19.9%) and less ALCLs (14.2%) in our cohort than in western country, and this geographic variation was also observed by other studies.4, 9, 13, 37
Almost all PTCLs and NKTCLs were aggressive and associated with poor prognosis, except ALK-positive ALCL. ALK-status influenced the treatment response and outcome significantly.38
Besides, several studies were reported to identify prognostic factors in patients with PTCL, such as Ki-67, absolute lymphocyte count, pretreatment serum total protein, IPI score and PIT score.12, 23, 39, 40, 41, 42, 43, 44, 45
Initial multivariate analysis in all PTCLs and NKTCLs showed that ALCL subtype and age more than 60 years were most important variables. Thus, we analyzed patients with ALCL separately. There were only six patients with ALK-positive ALCL in our study therefore, we combined ALK-positive and ALK-negative ALCL for analysis. The difference of outcome between ALK-positive and -negative ALCL was not significant statistically in our patient cohort.
In patients with non-ALCL PTCL, age >60 years, fever, BM involvement, elevated LDH level, thrombocytopenia, hypoalbuminemia and failure to achieve CR affected the outcome independently. In patients with ALCL, age >60 years, PIT >1 and failure to achieve CR were independent negative prognostic factors.
In comparison with aggressive B-cell lymphoma, the result of conventional chemotherapy was poor. CHOP remained the standard chemotherapy. A recent study showed that etoposide combined with CHOP may improve the outcome in young patients with PTCL.46
Alemtuzumab, an anti-CD 52 monoclonal antibody, was combined with CHOP as induction chemotherapy in patients with PTCL. Gallamini et al.47
reported a wonderful result that the CR rate achieved 70% although some manageable infections. But infection might limit the use of this agent. In salvage setting, pralatrexate, a novel antifolate agent, was approved as single agent in relapsed PTCL by the US Food and Drug Administration.48
The complete and partial response rates in 115 patients with relapsed or refractory PTCL were 10% and 17%, respectively.49, 50
ASCT or Allo-SCT had a role in salvage treatment or consolidation treatment for high-risk patients. Several prognostic models, including Ann Arbor stage classification, IPI score, PIT score and IPTCLP score, demonstrated their usefulness to identify high-risk patients. Gutiérrez-García et al.24
compared IPI, PIT, IPTCLP and modified PIT scores by CR rate, early mortality, 5-year DFS and 5-year OS. They concluded that IPTCLP score was the best score for OS, and IPI score had the best ability to predict CR. In Asia, similar studies were absent. We use logistic regression for analyses of CR rate and early mortality and AIC for correlation with OS. The AIC analysis, which is based on the Cox proportional hazards model, represents an overall assessment of the prognostic system and is the most important reference for the comparison across different staging systems. Thus, AIC was used for analysis of OS. In our study, Ann Arbor stage correlated with CR rate best (P
=0.006). This may be because larger tumor burden lowered the CR rate. IPI score, however, predicted early mortality and 3-year OS best.
In previous studies, intensive treatment, such as ASCT or Allo-SCT, showed improvements in OS and DFS as salvage treatment or consolidation therapy in high-risk patients. Despite inferior response to conventional chemotherapy, patients with PTCL did not have inferior outcome after ASCT in two studies.51, 52
In a salvage setting, the 3-year OS after ASCT was approximately 36–48%.53, 54, 55, 56, 57
In comparison with second-line chemotherapy, ASCT improved OS and DFS. There were several prospective trials about the role of frontline ASCT as consolidation therapy in high-risk patients.19, 58, 59, 60
The TRM was about 3–4.8% and 3-year OS rate ranged from 50 to 75%. The 12-year OS rate was 34% in one study by Corradini et al.58
Frontline ASCT appeared to be an effective approach for the consolidation in high-risk PTCL. Age-adjusted IPI score and β2-microglobulin can predict the outcome.54
Some PTCLs relapsed even after ASCT and Allo-SCT was tried in some patients. The rationale was the graft-versus-lymphoma effect.17, 61
But the data of Allo-SCT were limited in relapsed or high-risk PTCL with poor outcome, such as AITL, SPTCL or hepatosplenic γδ T-cell lymphoma.17, 61, 62, 63, 64, 65
Unfortunately, most patients with AITL were older than 70 years and cannot tolerate intensive treatment.66
Because of the benefits of HSCT overweighed the acceptable TRM. We analyzed 31 patients receiving HSCT. Twenty-four and seven patients received ASCT and Allo-SCT, respectively. Fourteen patients (45.2%, thirteen ASCT and one Allo-SCT) were in CR status before transplantation. The TRM was 9.7%, 3-year OS rate was 80.6% and median OS was 71 months. The outcomes of patients receiving ASCT or Allo-SCT were even better than patients with low-risk IPI score, no matter in salvage setting or in consolidation setting (). The negative predictive factor in patients receiving HSCT was extranodal involvement more than one site. Ann Arbor stage, IPI, PIT neither IPTCLP scores did not affect the outcome of HSCT. Owing to the advances in ASCT or reduced-intensity Allo-SCT, patients with high-risk PTCL may benefit from these novel treatments without much toxicity or TRM.
Overall survival by Kaplan–Meier method of HSCT group, IPI score and non-HSCT group.
There were some limitations in our study, the retrospective design caused selection bias in interpretation of the data of HSCT. Besides, the sample size in several subtypes was too small to be analyzed separately. The NKTCL prognostic score was reported by Lee et al.67
including LDH, B symptoms, lymph nodes, N1-N3 involvement and advanced Ann Arbor stage. In our cohort, independent prognostic factors in patients with ENKL included age >60 years, ECOG PS >1, advanced stage, extranodal involvement >1 site, IPI score >1 and lymphopenia. By analyzing five scores (stage, IPI, PIT, IPTCLP and NKTCL scores) in our patients with NKTCL, PIT score (AIC: 120.726) was better than the other four scores in predicting OS. But the case number was too small to be analyzed without bias. (Supplementary Figure and Table
In conclusion, IPI score correlated with the OS in patients with PTCLs better than other three prognostic models. In NKTCL, PIT score was the ideal score in evaluating OS. Besides, Ann Arbor stage can predict the CR rate. Our study supported the use of HSCT in selected patients with PTCLs or NKTCLs, but prospective randomized trial are needed to confirm the benefit of frontline HSCT in high-risk patients responding to chemotherapy.