| Background:Primary Central Nervous System Lymphoma(PCNSL)is a rare but aggressive form of extralolar non-hodgkin’s Lymphoma(NHL),It is highly invasive,characterized by rapid progression and poor prognosis.At present,the diagnosis and treatment of this disease has become the focus of medical research.Clinically,chemotherapy is considered to be the most important treatment for PCNSL,and hd-mtx based single drug or combination of other chemotherapy drugs is the most effective treatment.This topic through the retrospective analysis in June 2015 to December 2019 in the first hospital affiliated to China medical university during the period of hospitalization and the pathological diagnosis of complete cases of 45 patients with PCNSL and follow-up data,using by high-dose methotrexate for joint rituximab and temozolomide(HD-MTX + R + temozolomide)scheme comparison of single drug high-dose methotrexate(HD-MTX and high-dose methotrexate combined rituximab,respectively for the temozolomide solution(HD-MTX + R,HD-MTX + temozolomide),comparing the clinical curative effect between the treatment group,At the same time,the clinical and pathological features of the collected patients were analyzed for prognosis,so as to provide guidance and help for the clinical treatment of PCNSL patients.Method:Inclusion criteria and exclusion criteria: a retrospective study was conducted on PCNSL patients with initial treatment and normal immune function who were hospitalized in the first affiliated hospital of China medical university from June 2015 to December 2019.Inclusion criteria :(1)the pathological diagnosis and immunohistochemistry on which the diagnosis was made were based on the pathological report of the pathology department of our hospital.(2)other secondary factors were excluded to cause CNS,which was confirmed by imaging examination(including brain enhanced CT,MRI,testicular ultrasound,slit lamp examination of the eye or pet-ct of the whole body)and bone marrow biopsy.(3)initial treatment of patients who had not received any other treatment prior to diagnosis.(4)patients with complete clinical information and long-term follow-up.Exclusion criteria :(1)patients with confirmed congenital immune deficiency and HIV patients.(2)patients who need long-term use of immunosuppressive agents,such as rheumatism and immunity disease with prolonged illness,post-transplant status,etc.(3)have other malignant tumors or severe blood diseases.(4)patients who have received other anti-tumor therapies such as chemotherapy,radiotherapy and targeted therapy.According to the above inclusion and exclusion criteria,the clinical data of PCNSL patients meeting the criteria were grouped according to their clinical characteristics and different treatment regimens:(1)according to the clinical characteristics of the patients: gender(male or female);Age(> 60 years old or ≤60 years old);ECOG score(< 2 or ≥2);Serum lactate dehydrogenase level(the normal range of serum LDH in our hospital is 135-225 IU /m L,which can be classified as normal or elevated);Serum level of 2 microglobulin(the normal value range of serum 2 microglobulin in our hospital is 0.7-1.8mg/L,which can be classified as normal or elevated).Whether the deep brain structure is involved;Whether the lesions are multiple.(2)according to the results of pathology and immunohistochemical examination,the patients were divided into four groups: source of germinal centers(GCB or nonGCB);Ki-67(80% or higher,<80%).Whether bcl-6 is expressed;Whether bcl-2 is expressed;Expression of c-myc protein(≥40%,<40%).All immunohistochemical results were subject to the results of the department of pathology in our hospital.(3)according to the chemotherapy regimen,the groups were: the high-dose methotrexate combined with rituximab and temozolamide group(hd-mtx+R+ temozolamide),the high-dose methotrexate combined with rituximab group(hd-mtx + temozolamide),the high-dose methotrexate combined with rituximab group(hd-mtx + temozolamide),the high-dose methotrexate combined with temozolamide group(hdmtx + temozolamide),and the high-dose methotrexate alone group(hd-mtx).Curative effect evaluation standard adopt IPCG(International PCNSL Collaborative Group)standard:(1)CR(complete remission,)is defined as: cerebral MRI showed lesions disappeared completely,no evidence of lymphoma,eye CSF cytology negative(assessment 2 weeks ago to stop using corticosteroids);(2)PR(partial remission): brain tumor residual lesions in MRI or eye check ups are reduced more than 50%;(3)PD(progressive disease): new lesions,recurrence or tumor lesions increased by more than 25% compared with previous;(4)SD(stable disease): other conditions between remission and progression;ORR(Overall response rate)is the percentage of PR and CR population in the total populationSPSS25.0 software was used for statistical analysis,Fisher exact probability method was used to compare relevant factors of classification data between groups,kaplan-meier method was used for survival analysis,survival rate was compared by log-rank test,and Cox proportional risk regression model was used for multi-factor survival analysis.All reported P values were bilateral,and P < 0.05 indicated statistically significant differences.Results:1.Clinical characteristics: according to the inclusion criteria and exclusion criteria,a total of 45 patients with PCNSL who were hospitalized in the first affiliated hospital of China medical university from June 2015 to December 2019 met the requirements,with the following characteristics: 25(55%)males and 20(45%)females,with a malefemale ratio of 1.25 to 1.At the time of diagnosis,the median age was 62 years old,with an average age of 62.2 years.Among them,17 cases(38%)were ≤60 years old,and 28 cases(62%)were 60 years old.ECOG score < 2 points in 26 cases(57.7%)and ≥2 points in 19 cases(42.3%).Serum LDH level was normal in 17 patients(37.7%)and elevated in 28 patients(62.3%).Serum 2 microglobulin was normal in 16 patients(35.5%)and elevated in 29 patients(64.5%).Deep brain structures were involved in 29 cases(64.4%).There were 13 patients in the high-dose methotrexate combined with rituximab and temozolamide group,10 patients in the high-dose methotrexate combined with rituximab group,8 patients in the high-dose methotrexate combined with temozolamide group,and 14 patients in the single-dose high-dose methotrexate group(hd-mtx).There was no statistical difference in the distribution of the basic conditions of the above patients among the chemotherapy groups(P > 0.05).45 cases of PCNSL patients,17 cases(37.7%)diagnosed by stereotactic biopsy,another 28 cases(62.3%)were confirmed by surgical operation excision,all pathological specimens by our department diagnosis of non-hodgkin’s lymphoma,pathological types were diffuse large B cell lymphoma,and pathological classification of 13 cases(28.9%)as the source of germinal center,32 cases(63.2%)as the source of the germinal center.In terms of clinical manifestations,the first symptoms of 30 patients(66%)were headache,nausea,vomiting and other symptoms of increased intracranial pressure.Twelve patients(26%)went to the hospital due to limb weakness and unsteady walking,one(2%)due to blurred vision and diplopia,one(2%)due to first language disorder,one(2%)due to occasional consciousness disorder,and one(2%)due to symptom B.2.Efficacy analysis: among the 45 patients,there were 11 cases of CR(24.4%),27 cases of PR(60.0%),7 cases of PD(15.6%)and no SD.(1)high-dose methotrexate combined with rituximab and temozolamide group(hd-mtx +R+ temozolamide): 8 of the 13 patients obtained CR,4 obtained PR,the CR rate was 62%,the ORR was 92%,and 1 patient developed PD during chemotherapy.(2)high-dose methotrexate combined with rituximab group(hd-mtx +R): 1 of the 10 patients obtained CR,7 obtained PR,CR rate was 10%,ORR rate was 80%,and 2 patients developed PD during chemotherapy.(3)high-dose methotrexate combined with temozolomide group(hd-mtx + temozolomide): 1 of the 8 patients obtained CR,6 obtained PR,CR rate was 13%,ORR was 87%,and 1 patient developed PD during chemotherapy.(4)high-dose methotrexate group(hd-mtx)alone: among the 14 patients,1 patient obtained CR,10 patients obtained PR,the CR rate was 7%,ORR was 78%,and 3 patients developed PD during chemotherapy.3.Survival analysis: the median follow-up time of 45 patients was 16 months.During the follow-up period,31 patients survived and 14(31.1%)died,all of which were caused by disease recurrence or progression.In this study,the hd-mtx +R+ temozolomide and hd-mtx +R groups had short follow-up time and small sample size,so the median OS could not be estimated,so the average OS was used instead.The survival curves of four groups of combined chemotherapy regimens were plotted.OS(X =2.680,P=0.444)was not statistically significant,and PFS(X =16.388,P=0.001)was statistically significant.(1)high dose methotrexate combined with rituximab and temozolomide group(hd-mtx +R+ temozolomide): 1 of the 13 patients in this group died.The median PFS was 15 months,and the average OS was 26.1 months(95%ci: 22.6-29.6).(2)high-dose methotrexate combined with rituximab group(hd-mtx +R): 2 of the 10 patients in this group died.The median PFS was 10 months(95%ci: 7.4-12.5)and the average OS was 17.5 months(95%ci: 14.6-20.4).(3)high dose methotrexate combined with temozolomide group(hd-mtx + temozolomide): 3 of the 8 patients in this group died.The median PFS was 8 months(95%ci: 6.6-9.3),and the average OS was 22.8 months(95%ci: 18.1-27.6).(4)in the hd-mtx group,8 of the 14 patients died.The median PFS was 7 months(95%ci: 5.1-8.8),and the average OS was 24.6 months(95%ci: 17.6-31.3).4.Prognostic analysis: The 45 patients with follow-up were grouped according to age,gender,multiple lesions,deep brain structure,germinal center source,LDH level,beta-2 microglobulin level,ECOG score,ki-67,bcl-6,bcl-2,and c-myc.Unifactorial and multivariate analyses showed that non-germinal center source was an independent risk factor affecting prognosis(P < 0.05).Conclusions:1.Compared with rituximab,temozolamide and rituximab,the combination of large dose of methotrexate with rituximab,temozolamide and monotherapy methotrexate showed better efficacy in achieving complete remission after chemotherapy in patients with initial treatment of PCNSL.2.High-dose methotrexate combined with rituximab and high-dose methotrexate combined with rituximab,temozolomide and methotrexate,respectively,can prolong the progress-free survival of patients initially treated with PCNSL.3.Non-germinal center sources are independent risk factors for poor prognosis in PCNSL patients. |
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