Long-term complete response to anti-programmed-death-1 monotherapy in a patient with relapsed and refractory ovarian adenocarcinoma: A case report

BACKGROUND Ovarian cancer is the most common malignant tumor of the female reproductive system,and the survival rate of patients with relapsed and refractory ovarian cancer is very low.CASE SUMMARY Here,we report a case of high-grade serous papillary adenocarcinoma of the ovary that was successfully treated with immunotherapy.Radical surgery and adjuvant chemotherapy for the 56-year-old patient were successful;however,her tumor relapsed.Subsequent second-line chemotherapy,targeted agents,and other treatments were ineffective,as the tumor continued to recur and metastasize.Anti-programmed cell death-1(PD-1)monotherapy(tislelizumab)completely alleviated the tumor,and the multiple metastatic tumors disappeared.To date,the patient has used anti-PD-1 for 32 months,experiencing no disease progression and maintaining good health without additional treatment.CONCLUSION This case suggests that anti-PD-1 immunotherapy may have long-term positive effects on outcomes in some refractory recurrent solid tumors.Further research is needed to identify patients most likely to respond to anti-PD-1 therapy.

Venetoclax in combination with chidamide and dexamethasone in relapsed/refractory primary plasma cell leukemia without t(11;14):A case report

BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma(RRMM)with t(11;14).There are very few studies published on the use of venetoclax in pPCL without t(11;14).Similarly,histone deacetylase inhibitors are considered effective for the treatment of RRMM,but there are no reports on their use in pPCL.CASE SUMMARY A 57-year-old woman with severe anemia,thrombocytopenia,multiple bone destruction,impaired renal function,and 42.7%of peripheral plasma cells is reported.After multiple chemotherapy regimens and chimeric antigen receptor Tcell treatment,the disease progressed again.The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy.CONCLUSION The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.

Phase Ⅱ open-label study of recombinant circularly permuted TRAIL as a single-agent treatment for relapsed or refractory multiple myeloma

Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.

Anti-BCMA CAR-T Cell Therapy in Relapsed or Refractory Multiple Myeloma Patients with Impaired Renal Function

Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy in RRMM patients with renal impairment treated byanti-BCMA CAR-T cell therapy.A total of 59 RRMM patients were selected,and divided intoimpaired renal function(lRF)group[basclinc cstimated giomerular filtration rate(eSFR)<90 m/min/1.73 m^2(n=18)]and normal renal function(NRF)group(baseline eGFR≥90 mL/min/1.73 m,n=41).For patients with IRF,eGFR at the 6th month post-CAR-T cells infusion was significantlyhigher than the baseline(P<0.05).The multivariate analysis showed that light chain type and beta-2 micro-globulin(bcta-2M)were associated factors with the decrease of serum creatinine.Medianprogression-free survival(PFS)in the NRF group and IRF group was 266 days and 181 daysrespectively.Overall survival(OS)in the NRF group and lRF group was 877 days and 238 daysrespectively.There was no significant difference in the objective response rate(ORR)between thelRF group and the NRF group.It is suggested that CAR-T cells therapy could improve the renalfunction during the treatment of RRMM.The renal function could be more significantly improvedin RRMM patients with light chain type than with other types.

Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia： potential contribution to AML proqression

Acute myeloid leukemia （AML） is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair （MMR） function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease Datho8enesis.

Treatment of refractory/relapsed extranodal NK/T cell lymphoma with decitabine plus anti-PD-1:A case report

BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clinical outcome.Although L-asparaginase-based chemotherapy has improved the response rates of relapsed/refractory(R/R) ENKL,relapse occurs in up to 50% of patients with disseminated disease.CASE SUMMARY Immune evasion has emerged as a critical pathway for survival in ENKL and may be effectuated via STAT3-driven upregulation of programmed cell death ligand 1(PD-L1) or other molecular pathways.Anti-PD-1 is effective for R/R ENKL with EBV-driven upregulation of PD-L1 expression.Anti-PD-1 combined with decitabine showed positive preliminary results in a patient with R/R ENKL and resistance to anti-PD-1.CONCLUSION The treatment experience,in this case,demonstrated the potential ability of decitabine combined with PD-1 inhibitor to treat R/R ENKL,thus providing a new treatment strategy for this tumor.

Dengue causing relapse of minimal change disease: A double-edged sword

Dengue virus infection is endemic in India with seasonal variations.It can lead to lethal consequences with plasma leakage and/or bleeding[1,2].Dengue shock syndrome has high mortality in developing countries like India.Dengue can cause functional proteinuria and even heavy proteinuria[3-6].Though dengue has been implicated to cause glomerulonephritis[7],to the best of our knowledge,dengue as a cause of relapse of minimal change disease(MCD)has not been reported.

Statistical evaluation of cluster formation of relapse in neuromyelitis optica spectrum disorder

Evaluating the cluster formation of clinical attacks in chronic relapsing diseases is an important statistical issue because the presence of attack clusters may influence therapeutic strategies for relapse prevention.We recently reported the occurrence of unevenly clustered attacks in patients with anti-aquaporin-4(AQP4)antibody-positive neuromyelitis optica spectrum disorder(NMOSD)(Akaishi et al.,2020a).

Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al.The authors identified higher serum immunoglobulin(Ig)G4 levels and age over 55 years as independent risk factors for disease relapse.Despite notable strengths,it is crucial to address potential biases.Firstly,the cohort study included 189 patients with autoimmune pancreatitis(AIP)type 1(with higher IgG4 seropositivity and higher relapse)and 24 with type 2(with lower IgG4 seropositivity and lower relapse).Consequently,most,if not all,AIP type 2 patients were assigned to the normal group,possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse.Secondly,the authors did not provide sufficient details regarding AIP diagnosis,such as the ratio of definitive vs probable cases and the proportion of biopsies.In cases where histological evidence is unavailable or indeterminate,AIP type 2 may be misdiagnosed as definitive type 1,and type 1 may also be misdiagnosed as probable type 2,particularly in cases with normal or mildly elevated serum IgG4 levels.Lastly,in this retrospective study,approximately one-third of the consecutive patients initially collected were excluded for various reasons.Accordingly,the impact of nonrandom exclusion on relapse outcomes should be carefully considered.In conclusion,the paper by Zhou et al offers plausible,though not entirely compelling,evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse.The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping,heavily dependent on obtaining histological specimens.In this regard,endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process,contributing to mitigating biases in future explorations of the disease.

Surgical Treatment of Relapsed Clubfoot Using the Ilizarov Method: Anatomical and Functional Outcomes—A Report of 16 Cases at the Order of Malta’s Hospital Center

Introduction: Relapsed Congenital Talipes Equino Varus (CTEV) refers to clubfoot diagnosed after walking age. We refer to this entity as residual deformities of a previously treated clubfoot or a complete recurrence following treatment. For its treatment, several techniques have been used to improve the foot’s functional outcome while remaining minimally invasive. Correction by distraction using the Ilizarov external fixator is a promising technique. This single-center study aims to evaluate the anatomical and functional outcomes of treatment by distraction and compression with the Ilizarov fixator in relapsed club feet. Patients and Method: We carried out a retrospective, single-center study over 5 years. In total 16 clubfeet in 14 patients, including 9 males and 5 females were retained for final analysis. The average age of the patients at the time of the intervention was 15.16 years. K-wires were placed using the original technique. The average duration of the fixator in our series was 4.27 months. The functional assessment of patients was based on pre-and post-operative evaluation of the Foot and ankle function according to the AOFAS score. Results: Anatomic assessment was done according to the Dimeglio classification. There was a significant improvement at post-operative period with an average score of 4.47 against 10.07 at pre-operative period. We obtained 43.8% good and very good functional outcomes according to the global AOFAS score increasing from 63.07 at pre-operative period to 77.88 at post-operative period. Two cases of reinterventions were recorded. Conclusion: Distraction with the Ilizarov external fixator occupies a place of choice in the management of relapsed club foot. A good mastery of the technique and patient selection produce good functional outcomes.

Cyclops syndrome following anterior cruciate ligament reconstruction: Can relapse occur after surgery?

Symptomatic cyclops lesions are complications that can be seen at rates of up to approximately 10%after anterior cruciate ligament reconstruction.However,recurrent cyclops lesions have rarely been documented.There are case rare series in the literature regarding the treatment of recurrent cyclops lesion.Future large studies are needed to investigate factors contributing to the development of cyclops lesions and syndrome and treatment options.

Pomolidomide for relapsed/refractory light chain amyloidosis after resistance to both bortezomib and daratumumab:A case report

BACKGROUND Immunoglobulin light chain(AL)amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue,with cardiac involvement being very frequent(61%).Early diagnosis is of high importance because early initiation of treatment in AL amyloidosis may improve outcomes.Despite the administration of immunotherapeutic agents,in particular bortezomib and daratumumab,which have improved the outcomes of AL amyloidosis,antiplasma cell therapy remains suboptimal for some patients.CASE SUMMARY We report the case of a 55-year-old man presenting with heart failure who was diagnosed with cardiac AL amyloidosis by an endomyocardial biopsy.He experienced a short-term hematological remission with no organ response after being administered a bortezomib-daratumumab containing regimen.The treatment was switched to pomolidomide due to pulmonary involvement and progressive pleural effusion,in which flow cytometry analysis showed abnormal plasma cells.After two cycles of this regimen,the pleural effusion was controlled effectively with no recurrence.CONCLUSION This case emphasizes the crucial role of endomyocardial biopsy in early diagnosis of cardiac amyloidosis and suggests that pomolidomide may be an effective treatment for patients with AL amyloidosis that is relapsed/refractory to both bortezomib and daratumumab.

Chidamide,Decitabine,Cytarabine,Aclarubicin,and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia:A Retrospective Study from a Single-Center

Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.

Programmed cell death protein-1 inhibitor combined with chimeric antigen receptor T cells in the treatment of relapsed refractory non- Hodgkin lymphoma: A case report

BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.

An Evaluation of the Clinical Efficacy and Safety of Ixazomib for Relapsed/Refractory Multiple Myeloma

Objective:To investigate the clinical efficacy and safety of ixazomib in the treatment of relapsed/refractory multiple myeloma(RRMM).Methods:The clinical data of 20 patients with RRMM admitted to the hospital from January 2020 to January 2022 were analyzed retrospectively.All patients were treated with ixazomib-based chemotherapy regimen(IRD regimen 13 cases;ID regimen 7 cases).The objective response rate(ORR)and adverse events(AEs)were observed.Results:All 20 patients received two to seven courses of treatment,in which the median was three courses.One patient had CR,four patients had VGPR,seven patients had PR,two patients had SD,and six patients had PD.The ORR was 60.00%(12/20),and 25.00%(5/20)of them had VGPR or more.The ORR of patients with previous treatment lines≥3,ISS stage III,and high-risk cytogenetic was lower than that of patients with previous treatment lines<3,ISS stage I/II,and low-risk cytogenetics.The main AEs include anemia,thrombocytopenia,neutropenia,nausea and vomiting,diarrhea,constipation,and respiratory tract infection,most of which are grade I/II.Conclusion:Ixazomib is effective in the treatment of RRMM in some patients,and the AEs are controllable.Patients who had received less than 3 lines of treatment in the past,with ISS stage I to II and low-risk cytogenetics had better treatment effect.

Efficacy Observation of Pre-Excitation Regimen in the Treatment of Refractory Relapsed Acute Non-Lymphocytic Leukemia

Objective:To explore the clinical effect of applying the pre-excitation regimen in the treatment of patients with refractory relapsed acute non-lymphocytic leukemia(ANLL).Methods:This research work was carried out in our hospital(Shaanxi Provincial People’s Hospital)from September 2021 to September 2022.A total of 50 cases were selected for this study,and all were given a pre-excitation treatment plan,mainly low-dose cytarabine,aclarithromycin,etoposide,granulocyte colony-stimulating factor,and more were implemented.The clinical intervention effect was then analyzed.Results:Among the 50 patients in this study,the results showed that the treatment was very effective for 22 cases,accounting for 44.00%;effective for 14 cases,accounting for 28.00%;and ineffective for 14 cases,accounting for 28.00%.The total rate of effectiveness was 72.00%.The hematopoietic system adverse reactions of the patients were mainly bone marrow suppression.All 50 patients had different degrees of blood count decline,among which some patients’neutrophils were less than 0.5×10^(9)/L.The median time was 7 days.Among them,25 patients had infection problems,the incidence rate was 50.00%,the patient’s platelet count PLT<20×109/L,and the median time was 10 days.At the same time,among the 50 patients in this study,34(68.00%)patients had symptoms such as loss of appetite,nausea,vomiting,and fatigue,17(34.00%)patients showed hair loss,mildly elevated transaminases were observed in 8(16.00%)patients,and 11(22.00%)patients had muscle soreness.Conclusion:In the treatment of patients with refractory complex acute non-lymphocytic leukemia,the application of pre-excitation regimen has a significant effect,which can improve the adverse symptoms of patients,reduce the incidence of adverse reactions,and promote the recovery of patients.

Efficacy and Prognosis of Venetoclax Combined with Hypomethylating Agents in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Objective:To investigate the efficacy and prognosis of venetoclax combined with hypomethylating agents(HMAs)in the treatment of relapsed/refractory acute myeloid leukemia(AML).Methods:From June 2021 to February 2022,14 patients with relapsed/refractory AML were treated with venetoclax combined with HMAs,among which nine patients were treated with venetoclax+azacytidine,while five patients were treated with venetoclax+decitabine.The efficacy of the treatments was observed,and the patients were followed up.Results:All patients received one to five courses of treatment,in which the median course of treatment was three;four cases achieved CR and another four achieved PR,with NR in six cases;there was no treatment-related death.There were seven deaths up to the end of the follow-up period,all of which were progressive deaths at the end of the disease,and the overall survival rate was 50.00%.All the patients experienced different degrees of nausea,vomiting,and myelosuppression(Grade Ⅱ–Ⅳ),nine patients had Grade 3–4 hematological adverse reactions,and seven patients had infection.Conclusion:Venetoclax combined with hypomethylating agents is effective in the treatment of relapsed/refractory AML,with good prognosis,and some patients may even achieve CR.Although bone marrow suppression is serious with this combination,it is well tolerated.

Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn's disease patients

BACKGROUND Asymptomatic children with Crohn's disease(CD) require ongoing monitoring to ensure early recognition of a disease exacerbation.AIM In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse.METHODS In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn's Disease Activity Index, Creactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo.RESULTS 53 children were included and eighteen patients(34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse [median(interquartile range), relapse 723μg/g(283-1758) vs 244 μg/g(61-627), P = 0.02]. Fecal calprotectin levels > 250μg/g demonstrated good predictive accuracy of a clinical flare within 3 mo(area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937).CONCLUSION Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 μg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population.

Decitabine for Relapsed Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: At a median follow?up of 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement(HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement(HR = 11.70, 95% CI 2.24–60.99), and renal involvement(HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.