| Background and Purpose:Mature T/NK cell lymphomas are a set of malignant hematologic neoplasms that originate from mature T/NK cells,accounts for 20.1% of entirety lymphoma and 23.6% of non-Hodgkin lymphoma（NHL）.Mature T/NK cell lymphomas have highly heterogeneous and usually showed poor prognosis,rapid progresses.Peripheral T-cell lymphoma not otherwise specified（PTCL-NOS）,Angioimmunoblastic T-cell lymphoma（AITL）,systemic anaplastic large cell lymphoma（s ALCL）,extranodal NK/T-cell lymphoma,nasal type（ENKTL）are major subtypes of Mature T/NK cell lymphomas.According to the 2016 WHO criteria,containing more than two follicular helper T cells（TFH）immunophenotypes of PTCL-NOS was defined as peripheral T-cell lymphoma with TFH phenotype（PTCL-TFH）,originated from TFH cells which just like AITL.Currently,chemotherapies are limited in longterm survival.In recent years,Chidamide and Brentuximab Vedotin（BV）targeted drugs were listed in China in May 2015 and August 2020,respectively.This study retrospectively analyzed the characteristics of the main subtypes of mature T/NK cell lymphoma,and explored the effect of the targeted drugs（chidamide and BV）and hematopoietic stem cell transplantation on primary mature T/NK cell lymphomas of main subtypes in the Bethune First Hospital of Jilin University.Materials and Methods:（1）From August 2011 to October 2021,400 patients with mature T/NK cell lymphoma admitted to the Bethune First Hospital of Jilin University were retrospectively analyzed.330 cases of major subtypes were the main object of this study,including 119 ENKTL patients.110 AITL patients,53 PTCL-NOS patients,48 s ALCL patients.Baseline data of patients（age,gender,clinical stage,performance status,B symptoms,IPI score,PINK score,other malignant tumor,autoimmune disease）,pathological and laboratory examination data,treatment protocol,treatment efficacy（overall response rate,progression-free survival time,survival time）were collected.The study further collected 57 primary major subtypes of mature T/NK cell lymphoma patients treated with Chidamide and BV monoclonal antibody from May2015 to October 2021,to analysis the clinical efficacy and adverse reactions was performed.（2）Statistical analysis was performed using SPSS Statistics 26.0: Mann-Whitney U test and chi-square test were used to test the differences of sample data;Kaplan-Meier method Log-Rank test was used to compare the differences between groups of various treatments efficacy;Cox regression model was used to analyze the overall survival differences of major subtypes of mature T/NK cell lymphomas.Results:（1）Characteristics of mature T/NK cell lymphomas major subtypesGeneral characteristics: A total of 400 cases of mature T/NK-cell lymphoma,accounting for 20.1% of entirely lymphoma,and 23.6% of NHL.The major types were 330 cases including ENKTL（29.8%）,AITL（27.5%）,PTCL-NOS（13.3%）,and s ALCL（12.0%）,,accounting for 82.5% of entirety mature T/NK cell lymphomas.There were 39 cases of other subtypes,which were rare and only accounted for 9.8% of mature T/NK cell lymphomas.The median age was 57 years,and male to female ratio was 2:1.The analysis showed that mature T/NK cell lymphomas have a higher proportion,and ENKTL was the most common subtype among it.Clinical features: Among the 330 patients with major subtypes of mature T/NK-cell lymphomas,most patients with ENKTL were in stage I-II（57.8%）,less with B symptoms（46.2%）,and the majority in the low-risk group（51.7%）.Other subtypes（AITL,PTCL-NOS,s ALCL）were mostly in stage III-IV（78.7%-96.0%）,poor physical status（35.4%-76.4%）,and most associated with B symptoms（58.5%-68.5%）,the condition is more critical.The proportion of patients with other malignant tumors（3.6%）,autoimmune diseases（4.5%）was not high,and the AITL with autoimmune diseases（66.7%）had the highest proportion among other subtypes.It is suggested that early diagnosis is necessary,and patients with autoimmune diseases should be alert to the occurrence of AITL.Pathological features: Among the 330 patients,the CD30 expression rate was the highest in s ALCL（95.5%）;PTCL-NOS（45.9%）was the lowest;AITL（82.1%）and ENKTL（69.0%）were in the middle.The difference of CD30 expression rate could guide the treatment selection of CD30 monoclonal antibody.Treatment characteristics: Among the 330 patients,214 cases with primary and evaluable curative efficacy were included.The results showed that chemotherapy-based treatment was the first-line option,and 26.8% of patients received targeted therapy.The overall response rate（ORR）was the highest in s ALCL（84.2%）,the lowest in PTCL-NOS（53.6%）,and similar to ENKTL（77.5%）and AITL（78.0%）.Curative effects of mature T/NK cell lymphoma were related to the pathological type.Survival characteristics: Among the 330 patients,251 cases with initial treatment and ≥2courses of treatment were included.The median follow-up time was 34 months.The median progression free survival（PFS）was 17 months;the median overall survival（OS）was 24 months.5-year PFS more than 50% and OS more than 60% for major subtypes.s ALCL had the best prognosis（79.5% of 5-year PFS,80.5% of 5-year OS）,and PTCL-NOS had the worst prognosis（28.1% of 5-year PFS,22.4% of 5-year OS）,and there was a statistical difference（P<0.001）.And the prognosis of TFH-derived AITL and PTCL-TFH is moderate,which further confirms that survival characteristics is related to the pathological type.（2）Targeted therapy in major subtypes of mature T/NK cell lymphomaTargeted therapy（chidamide,BV）was used in 57 patients,and 88 patients with nontargeted therapy in control group.With a median follow-up of 32 months,ORR（85.7% vs71.6%）,2-year PFS（78.0% vs 53.6%）,and 2-year OS（81.0% vs 61.1%）,the targeted therapy group was significantly better than non-targeted therapy group,the difference was statistically significant（ORR: P=0.001;PFS: P=0.014;OS: P=0.031）.Subgroup analysis: 37 patients of Chidamide group and 88 patients of non-targeted group.The results showed that the Chidamide group was significantly better than the non-targeted group,with ORR（91.67% vs71.6%）,2-year PFS（73.2% vs 53.6%）,2-year OS（80.3% vs 61.1%）.The difference was statistically significant（ORR: P=0.017;PFS: P=0.019;OS: P=0.047）.And adverse reactions were tolerable.20 patients in the BV group comparing with 88 patients in the non-targeted group,ORR（75.0% vs 71.6%,P=0.759）,and 1-year PFS（88.2% vs 64.2%）,1-year OS（89.7%vs 70.1%）with significant difference（PFS: P=0.020,OS: P=0.037）,most adverse reactions was tolerated.The analysis of the CD30 expression and the efficacy of BV showed that the CD30 expression rate ≥ 60% was better than the CD30 expression rate < 60%,and ORR was statistically significant（100.0% vs 54.5%,P=0.038）.But 1-year PFS（100.0% vs 75.0%）and1-year OS（100.0% vs 80.8%）were not statistically significant（PFS: P=0.121,OS: P=0.178）.（3）hematopoietic stem cell transplantation in major subtypes of mature T/NK cell lymphomaThe analysis included 10 patients with autologous hematopoietic stem cell transplantation,and 50 non-transplant patients as control group.The median follow-up time was 23 months.The results showed that the survival of the transplant group was better than that of the nontransplant group,2-year PFS（87.5% vs 41.0%）and 2-year OS（78.9% vs 57.1）,but the difference was not significant（PFS: P=0.102;OS: P=0.102）.Conclusion:（1）This study included 400 cases of mature T/NK cell lymphomas,330 cases were major subtypes（ENKTL,AITL,PTCL-NOS,s ALCL）.Among the major subtypes,ENKTL is the most common.Consistent with the reported Asian ENKTL（29.75%）;（2）Among major subtypes,AITL,PTCL-NOS,and s ALCL are more critical in clinical,and AITL is prone to be merge within autoimmune diseases,which should be paid attention;（3）The expression rate of CD30 is the highest in s ALCL,and it is related to the efficacy of CD30 monoclonal antibody;（4）Survival analysis showed that s ALCL had the best prognosis and PTCL-NOS was the worst,suggesting that overtreatment and targeted therapies should be concerned on;（5）Targeted（chidamide,BV）therapy significantly improves the efficacy of major subtypes of mature T/NK cell lymphomas without increasing adverse reactions.Targeted therapy is an important clinical choice in future.（6）Hematopoietic stem cell transplantation is an option for consolidation therapy and second-line therapy to prolong patient survival. |
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