Prognostic Analysis Of Lymphoid Malignancies And Study On Targeted Therapy

PART? Clinical characteristics and prognostic analysis of 209 cases with B-cell chronic lymphoproliferative disordersTo discuss the correlation between clinical features,differential diagnosis,treatment and prognosis of B-cell chronic lymphoproliferative disorders,a retrospective study was conducted in 209 cases of B-cell chronic lymphoproliferative disorders.After collecting their clinical features,laboratory and imaging examination results,their relationship between initial conditions of disease,diagnosis methods,treatment protocols and prognosis were studied.Of the 209 patients,the male-female ratio was 2.67:1 with median age of 59(17-86)years.Median follow-up time was 33(2-331)months.The complete remission rate(CR),partial remission rate(PR),and overall response rate(ORR)was 59.7%,14.5% and 74.2% in CLL/SLL patients,54.5%,18.2% and 72.7% in FL patients,46.7%,26.7% and 73.3% in MCL patients,57.1%,21.4% and 78.6% in MZL patients,75.0%,8.3% and 83.3% in LPL/WM patients.There was no significant difference in survival time between patients diagnosed by lymph nodes/primary sites and those by bone marrow examination.Multivariate analysis indicated that elevated serum LDH or ESR level was independently associated with poor disease outcome.Patients who received chemotherapy combined with rituximab(67 cases)had a higher 5-year overall survival(53.9% vs 33.3%,P<0.05)than those without rituximab(16 cases).Flow cytometry showed that Monoclonal B lymphocyte proliferation usually indicated B-cell chronic lymphoproliferative disorders.Serum LDH and ESR level were adverse prognostic indicators.The site of diagnosis did not affect prognosis of the patients.Rituximab treatment in addition to chemotherapy might help to improve the clinical outcome.PART ? Clinical characteristics and prognostic factors of 225 patients with mature T-cell lymphoid malignanciesMature T-cell lymphoid malignancies comprise a group of heterogeneous diseases that vary in clinicopathological features,biological behavior,treatment response,and prognosis.Bone marrow(BM)infiltration is more commonly present in mature T-cell lymphoid malignancies compared with their B-cell counterparts and hence important for differential diagnosis.In this study,clinical characteristics and prognostic factors were analyzed in 225 patients with mature T-cell lymphoid malignancies treated in a single institution.These included 29 cases of T-cell lymphoproliferative disorders(T-LPD,all with BM infiltration)and 196 cases of T-/natural-killer-cell lymphoma(T/NKCL,56 with BM infiltration and 140 without BM infiltration).The estimated 5-year overall survival(OS)rates of T-LPD and T/NKCL were 96.6% and 37.3%,respectively.T-LPD patients were less likely to exhibit poor performance status,advanced disease stage,presence of B symptoms,or abnormal level of serum ?-2 microglobulin.With similar pathological characteristics,T/NKCL patients with BM infiltration showed significantly lower response rates and shorter OS than those without BM infiltration(P = 0.0264 and P < 0.0001,respectively).Multivariate analysis indicated that poor performance status,advanced disease stage,elevated serum lactate dehydrogenase level,and BM involvement were independent unfavorable prognostic factors.The Glasgow Prognostic Score may be more efficient than the International Prognostic Index in predicting disease outcome in T/NKCL.In conclusion,clinical characteristics may be useful in more effectively stratifying patients with mature T-cell lymphoid malignancies.PART ? Therapeutic effect of nanocomplex-based doxorubicin in lymphomaDrug resistance and disease relapse are two major problems of conventional chemotherapy,which have significantly decreased clinical efficacy of lymphoma treatment.We have successfully constructed a nano-gel complex that decrosslinks in tumor microenvironment and successfully loaded doxorubicin which is called Dex-SS-PMA-DOX.The complexes can easily disintegrate and decrosslink thus release doxorubicin in the weak acid environment.In this study,we compared the efficiency and toxicity of DexSS-PMA-DOX with traditional doxorubicin.In vitro,we find that the IC50 of Dex-SS-PMA-DOX is significantly lower than that in DOX,which means that its efficiency is higher than DOX.In vivo,we proved that Dex-SS-PMA-DOX inhibited tumor growth to a greater extent with less side effects than DOX.In addition,we further explored the specific possible molecular mechanisms involved.Dex-SS-PMA-DOX downregulated the expression of suvivin and upregulate the expression of cleaved Caspase-3 more than DOX.Also,DexSS-PMA-DOX reversed the drug resistance induced by DOX.Dex-SS-PMADOX reduced damage to normal tissue.Taken together,Dex-SS-PMA-DOX can be a new targeting therapeutic agent against lymphoma.