Analysis Of Adverse Prognosis Of Diffuse Large B Cell Lymphoma

Background and Objective:Lymphoma is a malignant tumor originating in lymph nodes and lymphoid tissue,it contains Hodgkin lymphom（HL）and non-Hodgkin lymphom（NHL）.According to the 2016 WHO classification,there are more than 170 subtypes of NHL,among which the most common subtype is diffuse large B-cell lymphoma（DLBCL）,which accounts for 30%-35%of all NHL.The current first-line therapy for DLBCL is CD20monoclonal antibody combined with anthracycline-based immunochemotherapy,targeted drugs and autologous hematopoietic stem cell transplantation have significantly improved the efficacy of patients with DLBCL,with about 60%to 70%cured,but 30%to 40%of patients still developing progression/recurrence.Regarding to the progression of DLBCL,there are clear adverse factors include such as clinical factors such as high risk of IPI and special-site lymphoma,as well as pathological factors such as cell origin,P53 mutation,and double hit lymphoma,while the early progress is not clear.Studies have found that most of the DLBCL patients occur porgression in the first 12-18 months,and the prognosis of this group of patients is poor,while the survival of patients without early progression is equivalent to that of the general population.However,there are no clear studies to define early progression of DLBCL,so we defined early progression of DLBCL as progression of disease within 24months after diagnosis（POD24）,in reference to the significance of POD24 in follicular lymphoma.Based on the above backgrounds,this study retrospectively analyzed the adverse prognostic factors of 458newly treated DLBCL patients,analyzed the incidence of POD24 in DLBCL patients,compared the survival of patients with and without POD24,and explored factors influencing POD24,so as to identify high-risk patients as early as possible,adjust treatment plan and improve long-term survival.Methods:The clinical data of 458 patients with DLBCL-not otherwise specified（NOS）who were newly diagnosed in the Department of Hematology,the First Hospital of Jilin University from January 2010 to January 2019 were retrospectively analyzed.The patients were followed up until January 2021,OS defined as the time between diagnosis of disease and death from any cause or the last follow-up.POD24 refers to recurrence or progression of disease within 24 months from diagnosis.SPSS 25.0 was used for statistical analysis,Kaplan-Meier method was used for survival analysis,and Log-Rank test was used for comparison between groups.The statistical data were tested byχ² test.Cox proportional hazards model and binary Logistic regression model were used for multivariate analysis.Results:1.Among the 458 DLBCL patients,the median follow-up time was52.0±1.5 months,the median age of the patients was 57（18-87）years old,244 patients（53.3%）were males,283 patients（61.8%）were≤60 years old,and 237 patients were stage III-IV（51.7%）,and 88 patients（19.2%）were bulky disease,IPI≥2 was found in 240 patients（52.4%）,lactatedehydrogenase was elevated in 207 patients（45.2%）;254 patients Ki-67%≥80（59.6%）,356 patients（77.7%）were non-GCB subtype;All patients treated with CHOP/CHOP-like±（R）chemotherapy,rituximab was used in 368 cases（80.3%）.The objective response rate was 90.4%and the complete response rate was 51.5%.The 1,3 and 5-year OS were90.2±1.4%,75.5±2.1%and 70.1±2.4%,respectively.2.Up to follow-up date,relapse/progression occurred in 163（35.6%）of 458 patients,and 131（80.4%）occurred progression of disease within24months（POD24）,accounting for 80.4%of that patients with recurrence/progression.3.Univariate analysis showed that age,clinical stage,maximum diameter of tumor,International Prognostic Index（IPI）score,lactate dehydrogenase（LDH）level,β₂ microglobulin（β₂-MG）level,using rituximab or not,whether POD24 occurred or not and whether CR was achieved or not after 4 cycles of treatment had statistical significance for OS of DLBCL patients（P<0.05）.4.According to the multivariate analysis,POD24 was the most significant independent prognostic factor in DLBCL patients（HR=17.788,P<0.001）.In addition to the POD24,the use of rituximab（HR=0.539,P=0.003）and the efficacy after 4 cycles treatment（HR=0.211,P=0.001）were independent prognostic factors in DLBCL patients.5.Univariate analysis showed that,clinical stage,B symptoms,IPI scores,the LDH level,theβ₂-MG level,the use of rituximab and CR or not were related to POD24（P<0.05）,among which,stage III-IV,not using rituximab and not achieved CR were independent impact factors for POD24（P<0.05）.For relative risk analysis,the hazard ratio for patients with a combination of these three risk factors for POD24 was 2.39.Conclusions:1.The progression of disease in DLBCL patients mainly occurred within 24 months after diagnosis（POD24）.2.POD24,using rituximab or not and efficacy of four courses were independent prognostic factors for DLBCL patients,and POD24 was the most significant factor for prognosis.3.Stage III-IV,not use of rituximab and not reach CR after 4 cycles of therapy were independent impact factors for POD24.Patients with these three factors had a 2.39-fold risk of developing POD24.4.The application of rituximab can decreased the risk of POD24 and improve the OS in DLBCL patients.