| ObjectivePeripheral T-cell lymphomas(PTCLs)are defined as a heterogeneous group of lymphoproliferative disorders originating from mature T-cells or nature killer(NK)cells.Mature T-cell lymphomas manifest the immunophenotypic features of post-thymic T lymphocytes,which are derived from both ?? T-cells and ?? T-cells.Mature T-cell constitute approximately 10–15% of lymphoid malignancies.Most prognosis of patients diagnosed with PTCLs is dismal.For instance,the 5-year overall survival(OS)rate of patients diagnosed with PTCLs except for those with ALK-positive ALCL,is approximately 30%.The International Prognostic Index(IPI)is generally used in prognosis of PTCLs,In addition to the indicators in IPI,however,there are other prognostic factors associating with the outcome of patients diagnosed with PTCLs.Cytotoxic molecules(CM)are apoptosis-inducing molecules that are present in the azurophilic cytoplasmic granules of cytotoxic cells,which defend individuals against neoplastic processes and viral infections.PTCLs derived from cytotoxic cells may be more aggressive or acquire resistance to conventional chemotherapy regimens due to the release of a large number of CM,resulting in a worse prognosis.We conducted a retrospective study to investigate the relationship between the expression of CM and the prognosis of patients diagnosed with PTCLs,and try to provide some guidance for clinical treatment.Methods1.General information: We reviewed the medical records of 94 consecutive patients diagnosed with PTCLs from December 2010 to November 2017 in our hospital.The pathological diagnosis was made according to WHO 2016classification guidelines.Patients diagnosed with PTCL-NOS,ALCL(both ALK-positive and ALK-negative),AITL,HSTCL,subcutaneous panniculitis-like T-cell lymphoma(SPTCL)and enteropathy-associated T-cell lymphoma(EATL)were included in the cohort.Pathological diagnosis and immunohistochemical examination were performed by the pathology department.In the immunohistochemistry,either TIA-1,perforin or Gr B with positive expression was identified as CM positive.Clinical data,which included age,sex,clinical stage(performed according to Ann Arbor classification guidelines),IPI score,bone marrow involvement,abnormality in blood,treatment regimen,disease response and outcome,were derived from the patient records.All patients had clinical lesions that could be observed by CT before chemotherapy.They were treated with CHOP and GDPT approaches as the first-line a respectively,and the efficacy was evaluated after 4 cycles of chemotherapy.The chemotherapy regimen was changed for patients whose diseases were in stable or prgressed.All patients underwent at least 6 cycles of chemotherapy.This study was conducted in accordance with the principles of the Declaration of Helsinki.The study protocol was approved by the ethics committee of The First Affiliated Hospital of Zhengzhou University.This article does not contain any studies with animals performed by any of the authors.2.Assessment of adverse effects and response criteria: Treatment responses were classified according to International Harmonization Project criteria.Complete remission(CR)was defined as the disappearance of all clinical evidence of the disease,as well as the normalization of all laboratory values and radiologic findings1 that had been considered abnormal before starting the treatment.Partial remission(PR)was defined as a ?50% reduction in the tumor size.Progressive disease(PD)was defined as the presence of new lesions or enlargement of primary lesions(all deaths due to progression or treatment-related toxicities before treatment evaluation are included in PD).Stable disease(SD)was definedas any response that did not fall into the previously defined.The objective response rate(ORR)is the sum of CR and PR.OS rate was calculated from the date of diagnosis to the date of death or the latest follow-up.The progression-free survival(RFS)rate was applied only to patients attaining in CR.It was calculated from the end of first-line therapy to relapse.3.Statistical analysis: All data were analyzed using the Statistical Package for the Social Sciences(SPSS).The correlation between clinical characteristics of the two groups was analyzed by chi-square test.The OS curves were estimated using the Kaplan--Meier method.The factors independently associating with the OS were identified by multivariate analysis using the Cox proportional hazards regression model.All P--values were two sided,and values were regarded statistically significant at P?0.05.Results1.Clinical characteristics: The characteristics of the 94 patients diagnosed with PTCL are summarized in Table 1.The patient age ranged from 17 to 74 years,with a median age of 48 years.Among all patients,27 cases were PTCL-NOS,22 cases were AITL,32 cases were ALCL(17 cases of ALK+ and 15 cases of ALK-),6 cases were SPTCL,5 cases were EATL and 2 cases were HSTCL.There was a slight male preponderance,with a male-to-female ratio of 1.76.Of the 94 patients,10patients(10.6%)were in stage I,12 patients(12.8%)were in stage II,22patients(23.4%)were in stage III,and 50 patients(54.9%)were in stage IV.Forty-five out of 91(49.5%)patients presented with systemic symptoms,and 41 out of 91(40.1%)patients expressed at least one CM.Among them,23 patients expressed only one kind of CM(mainly TIA-1 or Gr B),and the remaining 18 patients expressed at least two kinds of CM.The IPI score was available for 91 out of 94(96.8%)patients,Specifically,37 out of 91(40.6%)patients were classified as low risk,28(30.8%)as intermediate--low,17(18.7%)as intermediate—high risk,9(9.9%)as high risk.Bone marrow involvement was found initially in 6 patients(6.38%),initial lactate dehydrogenase(LDH)values were higher than normal in 42 patients(44.7%),and human herpes virus(EBV)antibody was positive in 17 patients(18.1%).The clinical characteristics of the patients in the CM positive group(41 cases)and the CM negative group(53 cases)were balanced,with no statistical difference.2.Response and outcomes: After a mean follow-up of 28.1 months(range from2.1 to 74.0 months),the CR rate was 35.1%(33 out of 94 patients),the PR rate was30.9%(29 out of 94 patients),the PR and SD rate was 34.0%(32 out of 94 patients),and the ORR was 66.0%.Among them,the complete response rate(CRR)of CHOP group and GDPT group was 32.7% vs 38.1%,the ORR of CHOP group and GDPT group was 65.4% vs 66.7%.P values of both groups were higher than 0.05,showing no statistical difference.According to the expression of CM,the CRR was 29.3% in the CM positive group and 39.6% in the CM negative group,P > 0.05.The ORR in the negative CM expression group was higher than in the positive CM expression group(ORR:79.2% vs.48.8%,P<0.05).40(42.5%)patients died,and the cumulative probability of survival at 3 years was 63.4%.The median OS was 17.5 months(15 months for positive CM expression and 20 months for negative CM expression).The median PFS was 12 months(12.7months for positive CM expression and 12 months for negative CM expression).Respectively,the 3-year OS rate of patients with positive CM expression was 48.3%,and the 3-year OS rant of patients with negative CM expression was 76.7%.3.Survival analysis: The univariate analysis suggested that four factors significantly affected and shortened OS,namely,advanced stage(P=0.007),a high IPI score(P=0.002),bone marrow involvement(P=0.004)and CM expression(P=0.022).Multivariate analysis showed that high IPI score,bone marrow involvement and positive CM expression were the independent risk factors.Conclusions1.PTCLs patients with advanced stage,a high IPI score,bone marrow involvementand CM expression always have poor prognosis.2.CM expression is an independent prognostic factor of PTCLs. |
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