Analysis Of Therapeutic Effect And Prognostic Factors Of Peirpheral T-cell Lymphoma

Peripheral T cell lymphoma (PTCL) is a kind of malignant diseases originating frompost-thymus or mature T lymphocytes or natural killer cells with great heterogeneity. Inwestern countries, the percentage of PTCL in non-Hodgkin’s lymphoma was5-10%, whichwas much higher in Asia, around20-35%. The overall outcome of PTCL was poorer with the5-year survival rate of30%, comparing with B cell lymphoma. So far, there was still noeffective cure. In clinical practice, CHOP or CHOP like regimen is mostly applied. However,the efficacy of such regimens mentioned above was not good in patients with PTCL. Manystudies have already reported that HyperCVAD/MA regimen was effective in patients withALL/LBL, large-scale investigations on the effectiveness of which in patients with PTCLwas very limited. Thus, our present study aimed to retrospectively compared the clinicalefficacy, the survival status and adverse events of HyperCVAD/MA regimen and CHOP orCHOP like regimen in treating PTCL, which may be helpful in designing prospective clinicaltrials in future.In addition, the strategy for complex and intractable PTCL is still the key part in curingPTCL. Although stem cell transplantation and novel targeting drugs have already been widelyapplied, literature on the clinical characteristics and prognosis in patients with PTCL was stilllittle. So in the third part, the progressive survival and prognostic factors for recurrence wereanalyzed, which may provide data of a counterpart as control group for the furtherdevelopment of new drugs or regimen.Finally,as the pace of aging increases, epidemiological reports verified that theincidence of non-Hodgkin’s lymphoma was positively correlated with the age. Consideringthe heterogeneity of PTCL, factors such as the weakening of organ function, individualvariations on the sensitivity to drug and the like should be taken into consideration whenchoosing the best treatment for old patients. Studies on the prognostic factors and clinicalfeatures in old patients with PTCL will facilitate the subgrouping of patients and selection of regimen for clinical researches. And the second part of this thesis analyzed clinical data of63old patients with PTCL.Part1Comparative study on the efficacy of HyperCVAD/MA regimen and CHOP orCHOP like regimen in the treatment of primary PTCLAim: To compare the clinical effectiveness and survival of80patients with initial PTCLaccepting treatment of HyperCVAD/MA regimen and CHOP or CHOP like regimen.Methods: Retrospectively, patients with initial PTCL from June2007to December2012admitted into our department by Pathological diagnosis were enrolled. Patients treated byHyperCVAD/MA regimen (experimental group, n=23) and CHOP or CHOP-like regimen(control group, n=57) were categorized into2groups. Pathological diagnosis of NK/T celllymphoma, PTCL-NOS、ALCL(ALK-)、AITL were made based on histopathological findings.Median follow-up period was23months (6-72months).SPSS statistical software was used.Categorical data were expressed as percentages (n%) and chi-square or Mann-Whitney U testwas applied to compare between groups. Continuous data were expressed as median(inter-quantile range). The survival rate was calculated using Kaplan-Meier method andcompared by log-rank. P value <0.05was considered as statistically significant.Results:1. Clinical characteristics: median age were41and44years old; percentages of malepatients were52.2%and31.6%; patients with subtype of AITL, ALCL(ALK-), NK/T,PTCL-NOS were5and12,3and12,6and15,9and18; I-II and III-IV of Ann Arbor stagingwere9and22,14and35; IPI scores of0-2and3-5were15and29,8and28; median coursesof chemotherapy were7and6, respectively in experiment group and control group. And nosignificant differences were found (P>0.05) and the two groups were comparable.2. Rate ofremission (CR+PR) in experiment group was higher than that in control group (18[78.3%] vs31[54.4%], P=0.047). Courses of chemotherapy in order to achieve remission were4(3-6)and6(5-8)(P=0.004).3. Regardless of Ann Arbor staging, the remission rates of patientsaccepting HyperCVAD/MA regimen were still high (I-II, remission rates88.9%; III-IV, remission rates71.4%).4. Rates of remission in patients with IPI score of0-2(low risk)treated by HyperCVAD/MA regimen were higher comparing with control group, respectively(86.7%vs55.2%;p=0.037).5. patients in experiment group got remission, including subtypesof AITL（n=5,100%)、ALCL(ALK-)（n=3,100%)、NK/T（83.3%)、PTCL-NOS（55.6%).6. Long-term outcome: Progression-Free survival(PFS)(P=0.039) were significantlyimproved by HyperCVAD/MA regimen, especially the one-year cumulative survival PFS,butnot the2-year and3-year PFS and PFS cumulative survival rates（52.2%VS38.6%，P=0.156;39.1%VS17.5%,P=0.055）.Overall survival (OS) and3-year PFS cumulativesurvival rates were not significantly different（P＞0.05）.7. Adverse events: more patientswith HyperCVAD/MA regimen experienced leuocopenia (white blood cell count <1.5×109/L)(73.9%vs38.6%， P=0.004). But no significant difference on incidences of pulmonaryinfection and severe thrombocytopenia (Platelet <20×109/L)(P>0.05). Cardiac toxicity andsevere anemia were rarely observed and all the patients can tolerate.Conclusion: Early efficacy of HyperCVAD/MA program as induction regimen to PTCLexcept ALCL (ALK+) are superior to CHOP/CHOP-like regimen, worthy of promotion. Part2Survival status and prognosis analysis on61patients with first recurrence orprogressionAim: To retrospectively evaluate the recurrence or progression of PTCL and explore thepotential factors associated with prognosis.Methods: Patients with PTCL experiencing the first recurrence or progression from January2003to June2013admitted into our department were enrolled. All the patients had everachieved CR/PR/SD with chemotherapy. Characteristics on first recurrence or diseaseprogression were observed. Second progression-free survival (PFS) and OS after recurrence or progression were recorded with related factors analyzed. All the patients were followed upsince first recurrence or progression and median follow-up was72months (3-128). UsingSPSS22.0software, survival rate was analyzed by Kaplan-Meier method and tested bylog-rank and calculated by Life table method.survival. Multivariate analyses of ordinal andnominal categorical data were tested by Cox proportional hazards model and logisticregression, respectively. Chi-square was applied to compare between groups. P value <0.05was considered as statistically significant.Results:1. The median time at first recurrence or progression was10months with medianage of45years old. After recurrence or progression, median PFS and OS were5months and6months. Expected one-year and2-year OS rate are24%and14%;1year,2-year PFS rateare21%and13%.2. Lymph node recurrence was the favorable factor affecting PFSconsidering recurrence (P=0.013), and affecting trend was observed on the OS (P=0.088).Hepatic recurrence was the risk factor affecting PFS (P=0.046) but not OS (P=0.344). IPIscore>2was the independent risk factor affecting OS (P=0.023). Inefficacy was the factoraffecting PFS and OS (P<0.05). In55patients with first recurrence or undergoing treatmentafter progression, conclusion is the same.3. IPI score of＞2was the factor affecting theeffectiveness of continuing treatment (P=0.004).Conclusion: The prognosis for patients with recurrence or progression in PTCL was poorwith short survival time. IPI score was shown to be important to predict outcomes forrecurrence or progression. Part3Analysis on the clinical features and prognosis in63old patients with PTCLAim: To analyze the clinical features and prognostic factors of old patients with PTCL.Methods: Retrospectively,63patients with PTCL admitted into our department from January2005to May2013were enrolled, Median follow-up was13months (3-96), and4patientswere lost of contact. The effect on age at occurrence, gender, IPI score, LDH, β2-microglobulin, PS score, extranodal involvement,Ann Arbor staging,B symptoms, Ki67percentage, invasion of bone marrow, courses of chemotherapy, and the best efficacyachieved were observed. SPSS statistical software was used. Categorical data were expressedas percentages (n%) and chi-square or Mann-Whitney U test was applied to compare betweengroups. Continuous data were expressed as median (inter-quantile range). survival rate wasanalyzed by Kaplan-Meier method and tested by log-rank and calculated by Life tablemethod.multivariate analysis were conducted by Cox proportional hazards model.Results:1. The median survival time of63elderly patients with PTCL was13months,1-year,2-year,3-year cumulative survival rates were47%、41%and30%.2. ANOVA showed thatWhen the onset of LDH, β2MG increased median survival time was significantly shorter (8months VS39months, P <0.001); PS score≥2points, IPI score>2points, accompanied bybone marrow involvement, extranodal involvement(>1) patient survival time was significantlyshorter (8months VS38months, P <0.001;10months versus36months, P <0.001;6.5months VS15months, P=0.011;9months and16months, P <0.001); KI67<30%of patientswith better survival (<30%vs30-60%vs>60%;39months vs13.5months vs8.5months;P<0.001);Efficacy of remission (CR+PR) and to complete four or more cycles ofchemotherapy significantly prolonged survival time of patient（s36vs7.5months；P＜0.001；24months vs11months；＜0.001）.3. Multivariate analysis verified that IPI score, PS score,extranodal involvement(>1), invasion of bone marrow, efficacy and chemotherapy coursewere independent factors for predicting outcomes (P<0.05).Conclusion: As to old patients with PTCL, PS score, bone marrow involvement, IPI score,extranodal involvement>1is important for prognosis. Up to4courses of chemotherapy withCR achieved was important to improve the survival in old patients with PTCL.