Clinical Study Of Young Patients With High Risk Diffuse Large B-Cell Lymphoma(DLBCL)

Part1: Analysis on the clinical characteristics and therapeutic measure of yong patients with high risk DLBCLObjective: To summarize the clinical data of young patients with high risk DLBCL, analyze clinical characteristics, treatment measures and untoward effect.Methods: The clinical data of young(≤60years)age adjusted International Prognostic Index(aa IPI)score of 2 or 3 patients with DLBCL were collected. These patients were initially diagnosed and treated in Academy of Military Medical Sciences from January 2006 to May 2014. The efficacy and the potential predictors are carried on. The recorded information includes age, sexual, aa IPI score, Ann Arbor stage, ECOG score, number of site of extranodal invasion, whether bone marrow involvement or not, whether with B symptoms no not, serum lactic dehydrogenase(LDH), β2-MG,immunophenotype,BCL-2,Ki-67,treatment mode,recent curative effect,progression free survival,total survival. Statistics analysis is conducted with software SPSS13.0, Kaplan-Meier rule is used to draw survival curve, Log-rank checkout is adopted in the comparison of PFS and OS, including Rituximab combined with chemotherapy group and simple chemotherapy group,the recent curative effect satisfies CR/CRu group and the recent curative effect not satisfies CR/CRu group,ASCT group and no adopted ASCT group,and P<0.05 is deemed as having statistical significance.Results: 1. The median age of the total 120 cases is 42(13~60) years old, sexual proportion is 1.1:1, 53 cases(44.2%) with aa IPI score equals to 2, 67 cases(55.8%) with aa IPI score equals to 3, 3cases(2.5%) with Ann Arbor stage II, 22cases(18.3%) with Ann Arbor stage III, 95cases(79.1%) with Ann Arbor stage IV, 34 cases(28.3%) with ECOG scores from 0 to 1, 86 cases(71.65%) with ECOG scores from 2 to 4, 22cases(18.3%) with site of extranodal invasion no more than 1, 98 cases(81.7%) with site of extranodal invasion no less than 2, 10 cases(8.3%) with bone marrow involvement, 4 cases(3.3%) with combined central invasion, onset with B symptom 68 cases(56.6%), LDH rising 101cases(84.1%), β2-MG rising 41 cases(34.2%), non-GCB 74cases(61.6%), GCB 30cases(25%), positive BCL-2 42 cases(35%), negative BCL-2 14 cases(11.7%), 57 cases(47.5%) with Ki-67 no less than 75 percent,Rituximab combined with chemotherapy 91cases(75.8%),while combined CHOP 76cases(83.5%), CHOP 14cases(15.3%), Hyper-CVAD/MA 1 cases(1.2%), 32 cases(26.6%) with ASCT. 2. Of all the cases, PFS of 3 years equals to 53.25%, OS equals to 61.52%,the recent curative effect satisfies CR/CRu 66 cases(55%), PR 18cases(15%), ORR 70%, Rituximab combined with chemotherapy 91 cases, a mong which the recent curative effect satisfies CR/CRu 53 cases(58.2%), PR12(13.2 %), ORR71.4%, chemotherapy 29 cases among which the recent curative effect satisfies CR/CRu 13 cases(44.8%), PR6(20.6%), ORR65.5%. PFS of 3years for Rituximab combined with chemotherapy group and Simple chemotherapy group is 60.07% and 27.93% respectively(P<0.001), OS is 67.08% and 41.78% respectively(P=0.003). 3. Mainly untoward effects include arrest of bone marrow, gastrointestinal reaction, infection for both Rituximab combined with chemotherapy and Simple chemotherapy. Comparison P value is larger than 0.05 for both groups. 4. Of all the cases, the recent curative effect satisfies CR/CRu 66 cases, otherwise 54 cases, PFS of 3years for satisfied CR/CRu group and unsatisfies CR/CRu group is 78.20% and 18.70% respectively(P<0.001), OS is 87.96% and 25.95% respectively(P<0.001). 5. Among 32 cases with ASCT after treatment, PFS of 3years for Transplantation group and no Transplantation group is 70.30% and 44.52% respectively(P=0.02), OS is 77.47% and 54.15% respectively(P=0.02). Among 67 high risk cases, Transplantation equals 19(28.4%), others 48(71.6%), PFS of 3years for Transplantation group and no Transplantation group is 60.64% and 28.93% respectively(P=0.006), OS is 72.31% and 39.59% respectively(P=0.001). 6. Among ASCT group, all cases with IV level arrest of bone marrow, 20 cases(62.5%) with infection, within which bacterial infection 14 cases(70%), mycotic infection 2 cases(10%), virus infection 4 cases(20%); 28cases(87.5%) with Gastrointestinal reaction, within which I-II level 20cases(62.5%), III level 4 cases(12.5%), IV level 4cases(12.5%); 10 cases with Oral mucosa reaction, within which I-II level 7 cases(21.9%), III level 3cases(9.4%),without Transplant related mortality.Conclusions: 1. Young patients with high risk DLBCL is a strong invasion high heterogeneity of malignancy.2. The recent curative effect and long term survival of Rituximab combined with chemotherapy are better than simple chemotherapy. 3. Untoward effects of Rituximab combined with chemotherapy and simple chemotherapy which can be tolerated include arrest of bone marrow, Gastrointestinal reaction, infection. Improved after treatment for both groups, untoward effects shows no difference in statistics. 4. Survival rate of recent curative effect satisfies CR/CRu group is better than the recent curative effect not satisfies CR/CRu group. 5. ASCT after treatment can improve the recent curative effect and long term survival, parts of cases(aa IPI=3) are liable to benefit from it. 6. No serious untoward effect appears during autologous hematopoietic stem cell transplantation, and it can be tolerated. Keywords:Part2: Analysis of prognostic factors for young patients with high risk DLBCLObjective: To summarize clinical data of young patients with high risk DLBCL, analyze clinical factors(sexual, aa IPI score, Ann Arbor stage, ECOG score, number of site of extranodal invasion, whether bone marrow involvement or not, whether with B symptoms no not, LDH level, β2-MG,peripheral blood lymphocyte count(PBLC), The count of peripheral blood mononuclear cells, Hb, the level of serum albumin, D-dimer), pathological factors( immunophenotype, BCL-2, Ki-67), The recent curative effect and Rituximab combined with chemotherapy, the relationship between ASCT after treatment and prognosis.Methods: The clinical data of young(≤60years)age adjusted International Prognostic Index(aa IPI)score of 2 or 3 patients with DLBCL were collected. These patients were initially diagnosed and treated in Academy of Military Medical Sciences from January 2006 to May 2014. We make analysis about the prognosis relationship between all the factors and the recent curative effect, PFS, OS. Statistics analysis is conducted with software SPSS13.0, X2 checkout is adopted in the relationship between all the factors and the recent curative effect, Log-rank checkout is adopted in the single factoranalysis, multi-factors adopts COX regression analysis if not pre-requisite, and P<0.05 is deemed as having statistical significance.Results: 1. Of all the cases, recent curative effect has no correlation with sexual, aa IPI socre, Ann Arbor stage, ECOG score, number of site of extranodal invasion, LDH, β2-MG, ALC, AMC, Hb, albumin, BCL-2, Ki-67. While it has correlation with whether Bone marrow involvement or not(P=0.008), whether with B symptoms no not(P=0.03), D-dimer(P=0.016), immunophenotype(P<0.001), ASCT(P=0.002). Combined bone marrow involvement, B-symptoms, D-dimer rising, non-GCB, non AHSCT after treatment shows recent curative effect depressed. 2. Single factor analysis shows that, the recent curative effect(P=0.00), Rituximab combined with chemotherapy(P=0.00), and AHSCT(P=0.002) have correlation with PFS; B-symptoms(P=0.006), D-dimer(P=0.025), Hypoproteinemia(P=0.003), the recent curative effect(P=0.00), Rituximab combined with chemotherapy(P=0.003), ASCT(P=0.002)has correlation with OS. While other single factor analysis such as sexual aa IPI score, Ann Arbor stage, ECOG score, number of Site of extranodal invasion, LDH, β2-MG,ALC, AMC, Hb, BCL-2, Ki-67 dose not have statistical significance(P>0.05). 3. Multi-factor analysis applying COX model shows that the recent curative effect(P=0.000) and ASCT(P=0.033) are the independent prognostic factors which can have effect on PFS. The recent curative effect(P=0.000) is the independent prognostic factor which can have effect on OS.Conclusions: 1. As for young patients with high risk DLBCL, combined bone marrow involvement, B-symptoms, D-dimer rising, non ASCT after treatment shows recent curative effect depressed. 2. The recent curative effect, Rituximab combined with chemotherapy, ASCT are prognostic factors which can have effect on PFS. B symptoms, Hypoproteinemia, D-dimer rising, depressed recent curative effect, without Rituximab combined with chemotherapym, non ASCT after treatment are ill prognostic factors which can have effect on OS. 3. The recent curative effect is the independent prognostic factors which can have effect on both PFS and OS. 4. Rituximab combined with chemotherapym can improve prognosis, whilewhether it can be deem as an independent prognostic factor cannot be concluded now. 5. ASCT is an independent prognostic factor which has correlation with PFS; while whether it can be deem as an independent prognostic factor which has correlation with OS still needs a forward research.