RPRD1B/CREPT facilitates the progression of diffuse large B-cell lymphoma by inhibiting apoptosis through the NF-κB signaling pathway

Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic target.Methods:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival analysis.In vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and apoptosis.Results:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor prognosis.In vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling pathway.Conclusions:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular proliferation.Targeting RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.

Identifying relevant factors influencing cancer-related fatigue in patients with diffuse large B-cell lymphoma during chemotherapy

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a rapidly growing malignant tumor,and chemotherapy is one of the treatments used to combat it.Although advancements of science and technology have resulted in more and more patients being able to receive effective treatment,they still face side effects such as fatigue and weakness.It is important to thoroughly investigate the factors that contribute to cancer-related fatigue(CRF)during chemotherapy.AIM To explore the factors related to CRF,anxiety,depression,and mindfulness levels in patients with DLBCL during chemotherapy.METHODS General information was collected from the electronic medical records of eligible patients.Sleep quality and mindfulness level scores in patients with DLBCL during chemotherapy were evaluated by the Pittsburgh Sleep Quality Index and Five Facet Mindfulness Questionnaire-Short Form.The Piper Fatigue Scale was used to evaluate the CRF status.The Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to evaluate anxiety and depression status.Univariate analysis and multivariate regression analysis were used to investigate the factors related to CRF.RESULTS The overall average CRF level in 62 patients with DLBCL during chemotherapy was 5.74±2.51.In 25 patients,the highest rate of mild fatigue was in the cognitive dimension(40.32%),and in 35 patients the highest moderate fatigue rate in the behavioral dimension(56.45%).In the emotional dimension,severe fatigue had the highest rate of occurrence,34 cases or 29.03%.The CRF score was positively correlated with cancer experience(all P<0.01)and negatively correlated with cancer treatment efficacy(all P<0.01).Tumor staging,chemotherapy cycle,self-efficacy level,and anxiety and depression level were related to CRF in patients with DLBCL during chemotherapy.CONCLUSION There was a significant correlation between CRF and perceptual control level in patients.Tumor staging,chemotherapy cycle,self-efficacy level,and anxiety and depression level influenced CRF in patients with DLBCL during chemotherapy.

Association of overall survival benefit of radiotherapy with progression-free survival after chemotherapy for diffuse large B-cell lymphoma:A systematic review and meta-analysis

Objective:To evaluate whether improved progression-free survival(PFS)from radiotherapy(RT)translates into an overall survival(OS)benefit for diffuse large B-cell lymphoma(DLBCL).Methods:A systematic literature search identified randomized controlled trials(RCTs)and retrospective studies that compared combined-modality therapy(CMT)with chemotherapy(CT)alone.Weighted regression analyses were used to estimate the correlation between OS and PFS benefits.Cohen’s kappa statistic assessed the consis-tency between DLBCL risk-models and PFS patterns.Furthermore,the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio(HR)according to the PFS patterns.Results:For both 7 RCTs and 52 retrospective studies,correlations were found between PFS HR(HRPFS)and OS HR(HROS)at trial level(r=0.639-0.876),and between PFS and OS rates at treatment-arm level,regardless of CT regimens(r=0.882-0.964).Incorporating RT into CT increased about 18%of PFS,and revealed a different OS benefit profile.Patients were stratified into four CT-generated PFS patterns(>80%,>60-80%,>40-60%,and≤40%),which was consistent with risk-stratified subgroups(kappa>0.6).Absolute gain in OS from RT ranged from≤5%at PFS>80%to about 21%at PFS≤40%,with pooled HROS from 0.70(95%CI,0.51-0.97)to 0.48(95%CI,0.36-0.63)after rituximab-based CT.The OS benefit of RT was predominant in intermediate-and high-risk patients with PFS≤80%.Conclusion:We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

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.

Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis, behavior and treatment

A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade &#x0003e; 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.

Clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma

Objective： To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma （DLBCL）. Methods： A retrospective study of 37 patients with primary testicular DLBCL was carried out from November 2003 to May 2012. Their clinical features, survival and prognostic factors were analyzed. Results： During a median follow-up period of 39.8 months （5.4-93.0 months）, the median progression-free survival （PFS） was 26.2 months （95% CI：0-65 months） and the 3-year overall survival （OS） rate was 78.4%. Within the whole cohort, the factors significantly associated with a superior PFS were limited stage （stage Ⅰ/Ⅱ）, lactate dehydrogenase （LDH） ≤245 U/L, international prognostic index （IPI） ≤1, primary tumor diameter 〈7.5 cm, and patients who had complete response （CR） and received doxoruhicin-contained chemotherapy （P〈0.05）. There was a trend toward superior outcome for patients who received combined therapy （surgery/ chemotherapy/radiotherapy） （P=0.055）. Patients who had CR, primary tumor diameter 〈7.5 cm and IPI score ≤1 were significantly associated with longer PFS at multivariate analysis. Conclusions： Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of orchectomy, doxorubicin-contained chemotherapy and contralateral testicular radiotherapy （RT） seemed to improve survival.

Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP

Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma(DLBCL)are available.This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients,and examine correlation of BCL2,TP53 and other genetic alterations with outcomes in patients treated with R-CHOP.Methods:Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL.MYC,BCL2,and BCL6 protein expressions were detected by immunohistochemistry.Results:The presence of BCL2 alterations significantly correlated with poor progression-free survival(PFS)(5-year PFS:13.7%vs.40.8%;P=0.003)and overall survival(OS)(5-year OS:34.0%vs.70.9%;P=0.036).Importantly,patients who harbored BCL2 gain/amplifications(BCL2GA/AMP)also had a remarkably inferior 5-year PFS(11.1%vs.38.3%;P<0.001)and OS(22.1%vs.69.6%;P=0.009).In contrast,neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival.Multivariable analyses showed that the presence of BCL2 alterations,especially BCL2GA/AMP,TP53 mutations,and International Prognostic Index(IPI)were significantly associated with inferior PFS and OS.Novel prognostic models for OS were constructed based on 3 risk factors,including BCL2 alterations(Model 1)or BCL2GA/AMP(Model 2),TP53 mutations,and IPI,to stratify patients into 4 risk groups with different survival outcomes.Conclusions:This study showed that DLBCL patients treated with R-CHOP,BCL2 alterations,especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes,which were independent of the IPI.The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP,but further validation of the prognostic models is still warranted.

Case report of acute-on-chronic liver failure secondary to diffuse large B-cell lymphoma

Acute liver failure is a rare presentation of hematologic malignancy. Acute on chronic liver failure(ACLF) is a newly recognized clinical entity that describes acute hepatic decompensation in persons with preexisting liver disease. Diffuse large B-cell lymphoma(DLBCL) is an aggressive non-Hodgkin's lymphoma(NHL) with increasing incidence in older males, females and blacks. However, it has not yet been reported, to present with acute liver failure in patients with preexisting chronic liver disease due to human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infection. We describe a case of ACLF as the presenting manifestation of DLBCL in an elderly black man with HIV/HCV coinfection and prior Hodgkin's disease in remission for three years. The rapidly fatal outcome of this disease is highlighted as is the distinction of ACLF from decompensated cirrhosis. Due to the increased prevalence of HIV/HCV co-infection in the African American 1945 to 1965 birth cohort and the fact that both are risk factors for chronic liver disease and NHL we postulate that the incidence of NHL presenting as ACLF may increase.

Extranodal involvement in young patients with diffuse large B-cell lymphoma： distribution, prognostic value and treatment options

Objective： Extranodal involvement represents a peculiar presentation of diffuse large B-cell lymphoma（DLBCL）. Previous studies have suggested that older patients are more prone to extranodal involvement. This study retrospectively addressed the distribution, prognostic value and treatment options of extranodal involvement in young patients with DLBCL.Methods： A total of 329 patients were enrolled according to the inclusion requirements. The effects of gender,extranodal involvement, age-adjusted international prognostic index（aa IPI）, rituximab infusion and radiotherapy on patient outcomes were evaluated.Results： Among these patients, 59% presented extranodal involvement in 16 anatomic sites. More than one instance was linked to many poorer clinical characteristics and poorer survival compared with either nodal disease or one instance. In patients with one extranodal lesion, multivariate analysis revealed that the site of extranodal involvement, but not the aa IPI or rituximab infusion, was independently related to the outcome, and radiotherapy had a negative influence on survival.Conclusions： Extranodal involvement is common in younger patients and exhibits a ubiquitous distribution.The site of extranodal involvement is of strong prognostic significance. Radiotherapy for extranodal lesions does not improve patient outcomes.

Addition of rituximab is not associated with survival benefit compared with CHOP alone for patients with stage I diffuse large B-cell lymphoma

Background： The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma （DLBCL） remains to be defined. We aimed to compare CHOP plus rituximab （R-CHOP） with CHOP alone and determine the value of radiotherapy in these patients. Methods： Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study. Results： Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response （CR） rate was 77% both in R-CHOP and CHOP groups （P=0.945）. After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival （PFS） （76% vs. 85%; log-rank P=0.215） and 5-year overall survival （OS） （90% vs. 96%; log-rank P=0.175） compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone （86% vs. 71%; log-rank P=0.005）. At multivariate analysis, patients who had CR （P=0.008） and received radiotherapy （P=0.003） were significantly associated with superior PFS. Conclusions： CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I or stage I non-bulky DLBCL patients.

Clinical Impact of t(14;18) in Diffuse Large B-cell Lymphoma

Objective： Recent studies have suggested that t（14;18） is present in a significant proportion of diffuse large B-cell lymphomas （DLBCLs）. However, the prognostic significance of this translocation and its relationship with BCL-2 protein expression remains controversial. Our study aimed to investigate the predictive power of t（14;18） and BCL-2 protein expression in the prognosis of DLBCLs. Methods： Biopsy specimens from 106 DLBCLs were analyzed using interphase fluorescence in situ hybridization （FISH）. Immunophenotypic analysis of CD20, CD3, CD10, BCL-6, MUM1 and BCL-2 was performed by immunohistochemistry. SPSS 13.0 software was used for statistical analysis. Results： The t（14;18） was identified in 27 of 106 cases （25.5%）. The percentages of tumor cells expressing CD10, BCL-6, MUM1 and BCL-2 were 21.7%, 26.4%, 56.6% and 73.6%, respectively. The presence of this translocation was significantly correlated with the expression of CD10 and immunophenotypic subtype （p0.001）. No association was observed between BCL-2 protein expression and the presence of t（14;18）. Multivariate analysis confirmed that both t（14;18） and BCL-2 expression were significantly associated with survival. Moreover, patients with t（14;18） had worse prognosis, compared with those with BCL-2 expression （for overall survival： hazard ratio, 4.235; 95%CI, 2.153-8.329, p0.001 vs. hazard ration, 2.743; 95%CI, 1.262-5.962, p=0.011）. Conclusions： The t（14;18） is a useful prognostic tool for the evaluation of DLBCL immunophenotype and prognosis. The prognosis of GCB （germinal centre-like B cell） DLBCL patients should be made with the consideration of the presence of this translocation, and the detection of t（14;18） should be included as a routine diagnostic test in these cases.

Gastric infiltration of diffuse large B-cell lymphoma: Endoscopic diagnosis and improvement of lesions after chemotherapy

Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of the non-Hodgkin’s lymphoma (NHL) accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-mo history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy (CT) scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.

Expression profile of CD10, Bcl-6, CD138, Bcl-2 and MUM1 and their prognostic value in 136 patients with diffuse large B-cell lymphoma

Objective： We evaluated the value of using a panel of GC B-cell （CD10 and Bcl-6） and activation （MUM1, CD138 and Bcl-2） markers by immunohistochemistry to define prognosis in patients with diffuse large B-cell lymphoma （DLBCL）. Methods： Two different models （Hans＇ and modified Chang＇s model） were applied on 136 de hove DLBCL patients. Median follow-up in all patients was 39 months （range 5-80 months）. Results： According to Hans＇ model, patients with GCB had much better overall survival （5-year OS, 75%） than those with non-GCB （5-year OS, 52%） （Kaplan-Meier survival analysis, P 〈 0.05, log rank test）. According to modified Chang＇s model, patients with group 1 had much better overall survival （5-year OS, 78%） than those with group 3 （5-year OS, 44%） while group 2 had no significant value compared with group 1 and group 3 in prognosis （Kaplan-Meier survival analysis, P 〈 0.05, log-rank test）. Using multivariate Cox proportional hazards regression analysis, the international prognostic index scores （IPI）, expression of CD138 and the expression pattern of modified Chang＇s model were independent prognostic indicators. Conclusion： Our results suggest that the expression patterns of the panel of GCB-cell and activation markers by immunohistochemistry correlate with prognosis of patients with DLBCL and both models can be used well in ordinary work.

Pneumocystis jirovecii and Legionella pneumophila coinfection in a patient with diffuse large B-cell lymphoma:A case report

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common non-Hodgkin's lymphoma.R-CHOP is a protocol for long-term chemotherapy for DLBCL patients.Longterm chemotherapy can lead to low immunity and increase the risk of opportunistic pathogen infections in immunocompromised patients.CASE SUMMARY We report a case of coinfection with Pneumocystis jirovecii(P.jirovecii)and Legionella pneumophila(L.pneumophila)in a patient with DLBCL.The patient was a 40-year-old female who was diagnosed with DLBCL and was admitted due to pulmonary infection.P.jirovecii and L.pneumophila were detected in her bronchoalveolar lavage fluid by hexamine silver staining,isothermal amplification and metagenomic sequencing.CONCLUSION To the best of our knowledge,this is the first case of P.jirovecii and L.pneumophila coinfection found in a DLBCL patient.Clinicians should be aware of the risk of complicated infection in patients undergoing long-term chemotherapy.

T-cell immunoglobulin mucin molecule-3, transformation growth factor β, and chemokine-12 and the prognostic status of diffuse large B-cell lymphoma

BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) have not been elucidated.AIM To examine the correlation between Tim-3,TGF-β and CXCL12 expression and DLBCL prognosis.METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups,respectively.The expression of Tim-3,TGF-β,and CXCL12 was detected immunohistochemically.Patients were followed up for 3 years,and progression-free survival was recorded.Cox mult-ifactorial analysis was performed to analyze the risk factors for poor prognosis.RESULTS The positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in DLBCL tissues than in non-cancerous(control) tissues(P < 0.05).One-year postsurgery,the positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment(P < 0.05).The 3-year progression-free survival of 97 patients with DLBCL was 67.01%(65/97).Univariate analysis revealed that clinical stage,bone marrow infiltration,International Prognostic Index(IPI) score,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were associated with poor prognosis(P < 0.05).Multivariate Cox regression analysis demonstrated that clinical stage Ⅲ–Ⅳ,bone marrow infiltration,mediate-to-high-risk IPI scores,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were independent risk factors affecting prognosis(P < 0.05).CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3,TGF-β,and CXCL12,and a high expression of all three indicates a poor prognosis.

The Lower Peripheral Blood Lymphocyte to Monocyte Ratio Following Completion of First Line Chemotherapy Is a Risk Factor for Predicting Relapse in Patients with Diffuse Large B-Cell Lymphoma

Background and objective: During routine follow up, there is no specific predictor to ascertain relapse after standard first line chemotherapy in diffuse large cell lymphoma. Therefore, this study was designed to assess the prognostic significance of the ratio between absolute lymphocyte and monocyte counts (LMR) in the peripheral blood to verify relapse in diffuse large B cell lymphoma. Patients and methods: A total of 139 patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) were evaluated and treated with CHOP or R-CHOP between the years 2009 and 2016. Three months following completion of first line therapy, Lymphocyte/monocyte ratio (LMR) was calculated from the routine automated complete blood cell count (CBC) attained a plateau after the bone marrow recovery after first line chemotherapy. The absolute lymphocyte count/absolute monocyte count ratio (LMR) was calculated by dividing the ALC by the AMC. Results: ROC curve analysis of 139 patients established 2.8 as cutoff point of LMR for relapse with AUC of 0.97 (95% CI 0.93 - 0.99, P ≤ 0.001). Cox regression analysis was performed to identify factors predicting relapse. In univariate regression analysis, ALC (95% CI 0.003 - 0.03, p ≤ 0.001), AMC (95% CI 15.4 - 128.8, p ≤ 0.001), LMR (95% CI 0.001 - 0.01, p ≤ 0.001), and LDH (95% CI 0.1 - 0.5, p ≤ 0.001) following completion of therapy are significant factors for relapse. Other significant factors for relapse are Ann Arbor stage (95% CI 1.1 - 6.9, P = 0.03), extranodal sites (95% CI 1.2 - 6.1, P = 0.01), age (95% CI 1.3 - 6.5, P = 0.01) and treatment of CHOP protocol (95% CI 0.05 - 0.6, P = 0.007). In a multivariate analysis LMR following completion of therapy was predictive for relapse (95% CI 0.001 - 0.2, P = 0.005). ALC was also significant in multivariate analysis (95% CI 0.01 - 0.8, P = 0.03). LDH following completion of therapy (95% CI 0.2 - 14.9, P = 0.5), AMC following completion of therapy (95% CI 0.3 - 43.1, P = 0.3), age (95% CI 0.9 - 205.4, P = 0.06), extra-nodal sites (95% CI 0.04 - 9.8, P = 0.8), Ann Arbor stage (95% CI 0.3 - 28.7, P = 0.3), and Treatment of CHOP protocol (95% CI 0.01 - 2.4, P = 0.2) were not statistically significant. Conclusion: This study observed that LMR assessed after first line chemotherapy during routine follow up is an independent predictor of relapse and clinical outcome in DLBCL patients. LMR at follow up can be used a simple inexpensive biomarker to alert clinicians for relapse during follow up after standard first line chemotherapy in DLBCL patients.

Cytomegalovirus enterocolitis in a patient with diffuse large B-cell lymphoma after chemotherapy with rituximab

Rituximab has been associated with the development of cytomegalovirus enterocolitis in immunosuppressed patients. A 51-year-old patient with diffuse large B-cell lymphoma who received a conditioning chemotherapy regimen (RCVP and RICE) consisting of rituximab before bone marrow transplantation went on to develop cy- tomegalovirus enterocolitis. This supports evidence from previously described cases that rituximab may be associ- ated with cytomegalovirus enterocolitis.

Disseminated soft tissue diffuse large B-cell lymphoma involving multiple abdominal wall muscles:A case report

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common subtype of non�Hodgkin lymphoma,and patients with DLBCL typically present rapidly growing masses.Lymphoma involving muscle is rare and accounts for only 5%;furthermore,multiple muscles and soft tissue involvement of DLBCL is unusual.Due to unusual clinical manifestation,accurate diagnosis could be delayed.CASE SUMMARY A 61-year-old man complained of swelling,pain and erythematous changes in the lower abdomen.Initially,soft tissue infection was suspected,however,skin lesion did not respond to antibiotics.18Fluoro-2-deoxy-D-glucose(18F-FDG)positron emission tomography-computed tomography demonstrated FDG uptake not only in the skin and subcutaneous tissue of the abdomen but also in the abdominal wall muscles,peritoneum,perineum,penis and testis.DLBCL was confirmed by biopsy of the abdominal wall muscle and subcutaneous tissue.After intensive treatment including chemotherapy with rituximab,cyclophosphamide,doxorubicin,vincristine and prednisolone,central nervous system prophylaxis(intrathecal injection of methotrexate,cytarabine and hydrocortisone)and orchiectomy,he underwent peripheral blood stem cell mobilization for an autologous hematopoietic stem cell transplantation.Despite intensive treatment,the disease progressed rapidly and the patient showed poor outcome(overall survival,9 mo;disease free survival,3 mo).CONCLUSION The first clinical manifestation of soft tissue DLBCL involving multiple muscles was similar to the infection of the soft tissue.

PHOSPHO1 Serves as a Key Metabolism-Related Biomarker in the Tumorigenesis of Diffuse Large B-cell Lymphoma

Objective:Diffuse large B-cell lymphoma(DLBCL)is an aggressive type of non-Hodgkin lymphoma.Due to its genetic heterogeneity and abnormal metabolism,many DLBCL patients have a poor prognosis.This study investigated the key metabolism-related genes and potential mechanisms.Methods:Differentially expressed genes,differentially expressed transcription factors(TFs),and differentially expressed metabolism-related genes(DEMRGs)of glucose and lipid metabolic processes were identified using the edgeR package.Key DEMRGs were screened by Lasso regression,and a prediction model was constructed.The cell type identification by estimating relative subsets of RNA transcripts algorithm was utilized to assess the fraction of immune cells,and Gene Set Enrichment Analysis was used to determine immune-related pathways.A regulatory network was constructed with significant co-expression interactions among TFs,DEMRGs,immune cells/pathways,and hallmark pathways.Results:A total of 1551 DEMRGs were identified.A prognostic model with a high applicability(area under the curve=0.921)was constructed with 13 DEMRGs.Tumorigenesis of DLBCL was highly related to the neutrophil count.Four DEMRGs(PRXL2AB,CCN1,DECR2 and PHOSPHO1)with 32 TF-DEMRG,36 DEMRG-pathway,14 DEMRG-immune-cell,9 DEMRG-immune-gene-set,and 67 DEMRG-protein-chip interactions were used to construct the regulatory network.Conclusion:We provided a prognostic prediction model based on 13 DEMRGs for DLBCL.We found that phosphatase,orphan 1(PHOSPHO1)is positively regulated by regulatory factor X5(RFX5)and mediates MYC proto-oncogene(MYC)targeting the V2 pathway and neutrophils.

Evaluation of a five-gene signature associated with stromal infiltration for diffuse large B-cell lymphoma

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common non-Hodgkin lymphoma.The development of immunotherapy greatly improves the patient prognosis but there are some exceptions.Thus,screening for better biomarkers for prognostic evaluation could contribute to the treatment of DLBCL patients.AIM To screen the novel mediators involved in the development of DLBCL.METHODS The GSE60 dataset was applied to identify the differentially expressed genes(DEGs)in DLBCL,and the principal components analysis plot was used to determine the quality of the included samples.The protein-protein interactions were analyzed by the STRING tool.The key hub genes were entered into to the GEPIA database to determine their expressions in DLBCL.Furthermore,these hub gene alterations were analyzed in cBioportal.The UALCAN portal was employed to analyze the expression of the hub genes in different stages of DLBCL.The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Score was conducted to evaluate the correlation between the gene expression and tumor purity.The gene-gene correlation analysis was conducted in the GEPIA.The stromal score analysis was conducted in TIMER to confirm the correlation between the gene expression and infiltrated stromal cells.The correlation between the indicated genes and infiltration level of cancerassociated fibroblasts(CAFs)was also completed in TIMER with two methods,MCP-Counter and Tumor immune dysfunction and exclusion.The correlation between fibronectin(FN1)protein level and secreted protein acidic and cysteinerich(SPARC)messenger ribonucleic acid expression was confirmed in the cBioportal.RESULTS The top 20 DEGs in DLBCL were identified,and the principal components analysis plot confirmed the quality of the significant DEGs.The pairwise correlation coefficient analysis among all samples showed that these DEGs have a certain co-expression pattern.The DEGs were subjected to STRING to identify the hub genes,alpha-2-macroglobulin(A2M),cathepsin B(CTSB),FN1,matrix metallopeptidase 9(MMP9),and SPARC.The five hub genes were confirmed to be overexpressed in DLBCL.The cBioportal portal detected these five hub genes that had gene alteration,including messenger ribonucleic acid high amplification and missense mutation,and the gene alteration percentages of A2M,FN1,CTSB,MMP9,and SPARC were 5%,8%,5%,2.7%,and 5%,respectively.Furthermore,the five hub genes had a potential positive correlation with tumor stage.The correlation analysis between the five genes and tumor purity confirmed that the five genes were overexpressed in DLBCL and had a positive correlation with the development of DLBCL.More interestingly,the five genes had a significant correlation with the stromal infiltration scores.The correlation analysis between the fives genes and CAFs also showed a significant value,among which the top two genes,FN1 and SPARC,had a remarkable co-expression pattern.CONCLUSION The top DEGs were identified,and the five hub genes were overexpressed in DLBCL.Furthermore,the gene alterations were confirmed and the positive correlation with tumor purity revealed the overexpression of the five genes and close association with the development of DLBCL.More interestingly,the five genes were positively correlated with stromal infiltration,especially in CAFs.The top two genes,FN1 and SPARC,showed a co-expression pattern,which indicates their potential as novel therapeutic targets for DLBCL.