| Objective:(1) This study was conducted to investigate the clinical characteristics and the efficac y of methods in the treatment of mantle cell lymphoma(MCL).(2) It was also conducted to preliminarily evaluate the prognostic implications of new molecules expressions in mantle cell lymphoma(MCL).Methods:1. Cases collectedThe pathological results of all lymphoma patients who confirmed by department of pathology of Xijing Hospital Affiliated to The Fourth Military Medical University during March 2007 to March 2012 were collected. The clinical data, in the process of initial diagnosis and subsequent treatment of the MCL of patients treated in our department were retrospectively analyzed, which included Sex, age, B-symptoms, ECOG physical status score, pathogenic site, the number of swollen lymph nodes, the largest volume of lymph nodes, spleen, bone marrow, and other outside invasion,clinical stage, the number ofwhite blood cells in the pathogenesis of MCL, lactate dehydrogenase, β2 – macroglobulin(β2-GM) and Ki-67.International Prognostic Index(IPI), Mantle Cell Lymphoma International Prognostic Index(MIPI)was adopted fordetailed evaluation.2. Pathological diagnosisThe pathological biopsy specimens of patients in our hospital were observed by light microscopy after 10% neutral formaldehyde fixed, paraffin embedding, conventional section, HE stain. The immune phenotype was detected by two steps method with streptomycin avidin-peroxidase, Labelled antibody including CD20, CD10, CD79 alpha, the Bcl-2, CD5, CD3, PAX5, Cyclin D1, and SOX11. Use phosphate buffer(PBS) as a negative control, and design slices as a positive control which can express some antigen.3. Treatment and prognostic analysisAll patients were treated with more than a course of the combined chemotherapy of CHOP(E) scheme [doxorubicin and cyclophosphamide, vincristine, and prednisone(etoposide)]+ Rituximab(R), and all drugs doses were used by referring to the standard dose of NCCN guidelines MCL treatments, calculated according to the body surface area. Patients maintain treatment who have the condition chose Autologous hematopoietic Stem Cell Transplantation(Autologous Stem- Cell Transplantation, ASCT) or PAD scheme [bortezomib(BTZ), adriamycin, dexamethasone] chemotherapy(R for maintain treatmentt). The short-term total response rate(overall response rate, ORR), was observal including complete remission(CR), partial remission(PR) after 2 ~ 4 cycles of chemotherapy; the overall survival(OS) and the progression-free survival(PFS) were observed for 2 years.4. Immunohistochemical detection of the protein expression of Mcl-1,NF-κB p65 and 14-3-3 zeta and analysis of clinical significanceObtain the pathological specimens of archive wax block of 12 patients with MCL in xiking hospital, and detect the protein expression of NF-κB B p65, MCL-1 and 14-3-3 zeta with re-slicing, re-fixed, using immunohistochemical staining method, analysis the relationship between the three and MCL staging, treatment and prognosis.Results:1. General clinical featuresDuring March 2007 to March 2012, a total of 2220 cases were confirmed lymphoma in our department, including Hodgkin lymphoma(HL) 150 cases(6.76%) and non-Hodgkin lymphoma(NHL) 2070 cases(93.24%), in which 1560 cases(75.36%) were B-NHL and 510 cases(24.64%) were T-NHL. 48 MCL cases accounted for about 3.1% of B-NHL and 2.1% of lymphoma. 23 MCL patients were treated in our hospital.Among the 23 MCL patients, the ratio of male to female was about 3:1 among which the average age was 57.39±9.13(43~76 years).(1) 21 cases had been tested CD20 and the positive rate was 100%. 21 cases had been detected Cyclin D1 and the Cyclin D1+ were 20 cases(95.2%). 1 case of Cyclin D1-(4.8%) had CD5+ and SOX11+. 19 cases have been tested CD5, 5 cases of CD5-(26.3%) were positive expression in Cyclin D1.(2) 21 cases had been detected Ki-67, positive rate 10%- 60%,10 cases were Ki-67≤30%(about 47.6%); 11 cases were Ki- 67 > 30%(52.4%).(3) 9 cases had been detected expression of SOX11 protein, 6 cases were positive cells > 20%(about 66.7%).(4) 21 MCL patients were in Ann Arbor stage Ⅲ-Ⅳ, about 91.3%. We calculated 23 patients’ IPI score, in which 17 cases were 0-2 points(low risk group, about 73.9%); 6 cases were 3-4 points(high risk group, about 26.1%). We calculated 22 patients’ MIPI score, in which 16 cases MIPI<5.7(low risk group, about 72.7%); 6 cases MIPI≥5.7(high risk group, about 27.3%).(5) 20 patients had been detected β2-GM, in which 8 cases of β2-GM<3mg/L(40%); 12 cases of β2-GM≥3mg/L(60%).(6) Followed up for 2 years, 12 patients survived, and the rate of 2y-OS was 52.2%; 8 cases were no progress, the rate of 2y-PFS was 34.8%.2. The evaluationof prognosis related factors shows that:2.1 Correlation analysis between prognosis and prognosis index(1) The rate of 1.5y- and 2y-PFS of grouping IPI 0-2(52.9%, 47.1%) were superior to grouping IPI 3-4 patients(0%, 0%)(P < 0.05]; but no statistical difference was found in ORR, OS rate.(2) The ORR rate of MIPI < 5.7 patients, the OS/PFS rate of 1.5 years, the OS / PFS rate of 2 years(81.3%, 75%/56.3%, 68.8%/50%) were bigger than that of the group of MIPI ≥ 5.7(33.3%, 16.7%/0%, 16.7%/0%)(P < 0.05).The results show that MIPIscore can better reflect the curative effect and prognosis of MCL than IPI score.2.2 Other prognostic factors analysis(1) The ORR rate of groupingβ2-GM<3mg/L patients(100%) is higher than that of groupingβ2-GM≥3 mg/L(50%)[P=0.024];no statistical difference is found in OS,PFS rate respectively.(2)No statistical difference is found between grouping Ki-67≤30% and grouping Ki-67>30% both in the rate of ORR, OS and PFS.(3) The 2y-OS rate of the SOX11 positive cell rate >20%(16.7%) is significantly lower than that of the SOX11 positive cell rate <20%(100%); but no statistical difference is found respectively in ORR and PFS rate.3. Treatment and prognosis23 patients with MCL were retrospectively analyzed, including 10 cases of patients with R and CHOP chemotherapy(E), 13 cases with simple CHOP chemotherapy(E), 3 cases with PAD chemotherapy. In 14 cases of refractory patients who recurred, 1 case accepts ASCT after chemotherapy and local radiotherapy reaching CR; 3 patients choose plan of PAD(BTZ, adriamycin, and dexamethasone) combination chemotherapy, including 2 cases with maintenance therapy using once a month after reaching CR. Prognostic analysis shows that:(1)the ORR rate and 2y-OS/PFS rate of 10 cases with scheme R+CHOP(E)(respectively 100%, 80%/70%) are all superior to that of 13 cases with scheme CHOP(E)(respectively 38.5%, 30.8%/7.7%)[P<0.05].(2)The ORR rate and 2y-OS/PFS rate(respectively 100%, 100%/66.7%) of 3 cases with scheme PAD are all superior to that of 13 cases(respectively 38.5%, 30.8%/7.7%) with scheme CHOP(E), but no significant statistical difference is found because the sample size is small.4. The expression of Mcl-1、NF-κB p65 and 14-3-3zeta protein and prognosis relevance in MCLIn 12 patients, The number of positive expression of Mcl-1, NF-κB p65 and 14-3-3zeta is 6, 6 and 8 and accounting for 50%, 50% and 66.7% respectively. Prognostic factors analysis shows that:(1) the ORR and 2y-OS/PFS rate of the patients with Mcl-1 positive expression(33.3%, 33.3%/16.7%) are all inferior to that of the patients with Mcl-1 negative expression(100%, 100%/83.3) [P<0.05].(2) The 2y-PFS rateof the patients with NF-κB p65 positive expression(16.7%) was inferior to that of the patients with NF-κB p65 negative expression(83.3%) [P=0.04]; the ORR and the 2y-OS rate of the patients with NF-κB p65 positive expression(50%, 50%) were inferior to that of the patients with NF-κB p65 negative expression(83.3%, 83.3%), due to low sample size, no significant statistical difference was found.(3) The ORR and the 2y-OS/PFS rate of the patients with 14-3-3zeta positive expression(8/12 cases) were all inferior to that of the 14-3-3zeta negative expression, but there was no significant statistical difference due to low sample size. The results above show that the Mcl-1, 14-3-3 zeta and nf-kappa B p65 protein are correlated with prognosis.Conclusion:1. This research shows that the incidence of MCL in our hospitalz was lower than the reported abroad.2. Among the diagnosed MCL patients, 20 Cyclin D1+ cases(95.2%) including SOX11+(66.7%). 1 case Cyclin D1-(4.8%), SOX11+. 5 cases CD5-, Cyclin D1+. Cyclin D1 is the golden standard for diagnosing MCL, and SOX11 help for pathological diagnosis of Cyclin D1- cases.3. The MIPI had better prognostic significance than the IPI. β2-GM and SOX11 were related to prognosis; and Ki- 67 prognostic relevance need to enlarge sample size for further study.4. R+CHOP(E) had better curative effective than that of the CHOP(E), PAD scheme combined R maintenance treatment increased the rate of OS/PFS. It is still necessary to expand the sample clinical observation.5. The positive rates of Mcl-1、NF-κB p65、14-3-3zeta protein express in 12 MCL cases were 50%, 50% and 66.7%, and the their expression were positively related to prognosis. These molecules might be new prognostic indicators which needs further research proved by increasing sample size. |
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