CD5-positive(CD5+)diffuse large B-cell lymphoma(DLBCL)represents a special subgroup of DLBCL with a more aggressive disease course and is more likely to develop into relapsed/refractory(r/r)DLBCL in response to immuno...CD5-positive(CD5+)diffuse large B-cell lymphoma(DLBCL)represents a special subgroup of DLBCL with a more aggressive disease course and is more likely to develop into relapsed/refractory(r/r)DLBCL in response to immunochemotherapy.The incidence of CD5+DLBCL is 5%–10%among DLBCL patients1.展开更多
Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin’s lymphoma(NHL)worldwide,accounts for 39% and 44% of nodal and extranodal NHL cases in China,respectively1.Standard first-line treatment for...Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin’s lymphoma(NHL)worldwide,accounts for 39% and 44% of nodal and extranodal NHL cases in China,respectively1.Standard first-line treatment for DLBCL is chemo-immunotherapy with rituximab,cyclophos-phamide,doxorubicin,vincristine,and prednisone,which cures 50%-60% of patients2.展开更多
AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treate...AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[scheduled as cyclophosphamide,doxorubicin,vincristine and prednisone (CHOP)and CHOP-like],and chemotherapy combined with rituximab(group B,n=30).The primary end point of the study was complete response(CR)rate;the secondary end points were disease-free survival (DFS)at 5 years and overall survival(OS).RESULTS:Median follow-up was 62 mo(range:31102 mo).We observed a significant difference between the two groups(A vs B)in terms of CR[76.6%(23/30) vs 100%,P=0.04)and DFS at 5 years[73.3%(22/30) vs 100%,P=0.03).To date,19 group A(63.3%) patients are alive and 11 have died,while all group B patients are alive.No significant differences in toxicity were observed between the two groups.CONCLUSION:Rituximab in combination with chemotherapy improves CR rate,DFS and OS.Further prospective trials are needed to confirm our results.展开更多
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 pa...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.展开更多
Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess t...Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess the antitumor effect of DHA on diffuse large B cell lymphoma cells and to determine the potential underlying mechanisms of DHA-induced cell apoptosis.Methods:Here,the Cell Counting Kit 8 assay was conducted to study cell proliferation.We performed Annexin V-FITC/propidium iodide staining,real-time polymerase chain reaction,and western blot analysis to analyze cell apoptosis and potential molecular mechanisms.Results:The results showed that DHA substantially suppressed cell proliferation and induced cell apoptosis in vitro in a time-and concentration-dependent fashion.Moreover,STAT3 activity could be inhibited after stimulation with DHA.Conclusion:These results imply that the underlying anti-tumoral effect of DHA may increase apoptosis in diffuse large B cell lymphoma cells via the STAT3 signaling pathway.In addition,DHA might be an effective drug for diffuse large B cell lymphoma therapy.展开更多
Objective： We studied the diagnosis and therapy of primary lung diffuse large B cell lymphoma （DLBCL）. Methods： Analysis the clinical manifestations, pathologic character and immunohistochemical character of one l...Objective： We studied the diagnosis and therapy of primary lung diffuse large B cell lymphoma （DLBCL）. Methods： Analysis the clinical manifestations, pathologic character and immunohistochemical character of one lung diffuse B cell lymphoma patent. Results： In visual observation, it＇s a gray irregular fobulated mass, section was gray, fish-like, and number of necrotic foci. Observed under the microscope, subepithelial respiratory center oocyte-like cells diffuse proliferative, infiltration in lung tissue. Immunohistochemistry： CD20 （＋）, CD79a （＋）, CD3 （-）, CD45RO （-）, PCK （-）. Conclusion： Diffuse large B cell lymphoma is the most common subtype in non-Hodgkin lymphoma, but the primary lung diffuse large B cell lymphoma is rare. This disease is lack of typical clinical manifestations, so easily misdiagnosed. The diagnosis of diffuse large B cell lymphoma should be based on pathology and immunohistochemistry.展开更多
BACKGROUND Central nervous system(CNS)lesions and peripheral neuropathy are rare among patients with non-Hodgkin’s lymphoma(NHL).Lymphomatous infiltration or local oppression usually accounts for CNS or peripheral ne...BACKGROUND Central nervous system(CNS)lesions and peripheral neuropathy are rare among patients with non-Hodgkin’s lymphoma(NHL).Lymphomatous infiltration or local oppression usually accounts for CNS or peripheral nerve lesions.The incidence of peripheral neuropathy was 5%.Guillain-Barrésyndrome(GBS)is rare and may occur in less than 0.3%of patients with NHL.Hemophagocytic syndrome(HPS)is a rare complication of NHL.It has been reported that 1%of patients with hematological malignancies develop HPS.Diffuse large B-cell lymphoma(DLBCL)combined with GBS has been reported in 10 cases.CASE SUMMARY We report the case of a 53-year-old man who was initially hospitalized because of abnormal feelings in the lower limbs and urinary incontinence.He was finally diagnosed with DLBCL combined with GBS and HPS after 16 d,which was earlier than previously reported.Immunoglobulin pulse therapy,dexamethasone,and etoposide were immediately administered.The neurological symptoms did not improve,but cytopenia was relieved.However,GBS-related clinical symptoms were relieved partially after one cycle of rituximab-cyclophosphamide,hydroxydaunorubicin,vincristine,and prednisone(R-CHOP)chemotherapy and disappeared after six cycles of R-CHOP.CONCLUSION GBS and HPS heralding the diagnosis of Epstein-Barr virus DLBCL are rare.Herein,we report a rare case of DLBCL combined with GBS and HPS,and share our clinical experience.Traditional therapies may be effective if GBS occurs before lymphoma is diagnosed.Rapid diagnosis and treatment of DLBCL are crucial.展开更多
BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common type of malignant lymphoma(ML),accounting for 30%-40%of cases of non-Hodgkin’s lymphoma(NHL)in adults.Primary paranasal sinus lymphoma is a rare prese...BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common type of malignant lymphoma(ML),accounting for 30%-40%of cases of non-Hodgkin’s lymphoma(NHL)in adults.Primary paranasal sinus lymphoma is a rare presentation of extranodal NHL that accounts for only 0.17%of all lymphomas.ML from the maxillary sinus(MS)is a particularly rare presentation,and is thus often difficult to diagnose.We have reported the first known case of DLBCL originating from the MS with rapidly occurrent multiple skin metastasis.CASE SUMMARY An 81-year-old Japanese man visited our hospital due to continuous pain for 12 d in the left maxillary nerve area.His medical history included splenectomy due to a traffic injury,an old right cerebral infarction from when he was 74-years-old,hypertension,and type 2 diabetes mellitus.A plain head computed tomography(CT)scan revealed a 3 cm×3.1 cm×3 cm sized left MS.On day 25,left diplopia and ptosis occurred,and a follow-up CT on day 31 revealed the growth of the left MS mass.Based on an MS biopsy on day 50,we established a definitive diagnosis of DLBCL,non-germinal center B-cell-like originating from the left MS.The patient was admitted on day 62 due to rapid deterioration of his condition,and a plain CT scan revealed the further growth of the left MS mass,as well as multiple systemic metastasis,including of the skin.A skin biopsy on day 70 was found to be the same as that of the left MS mass.We notified the patient and his family of the disease,and they opted for palliative care,considering on his condition and age.The patient died on day 80.CONCLUSION This case suggests the need for careful,detailed examination,and for careful follow-up,when encountering patients presenting with a mass.展开更多
BACKGROUNDOver the past 20 years,we have gained a deep understanding of the biologicalheterogeneity of diffuse large B cell lymphoma(DLBCL)and have developed arange of new treatment programs based on the characteristi...BACKGROUNDOver the past 20 years,we have gained a deep understanding of the biologicalheterogeneity of diffuse large B cell lymphoma(DLBCL)and have developed arange of new treatment programs based on the characteristics of the disease,bringing us to the era of immune-chemotherapy.However,the effectiveness andmolecular mechanisms of targeted-immunotherapy remain unclear in DLBCL.Targeted-immunotherapy may be beneficial for specific subgroups of patients,thus requiring biomarker assessment.CASE SUMMARYHere,we report a case of MCD subtype DLBCL with MYD88L265P and CD79Bmutations,considered in the initial stage as lymphoplasmic lymphoma(LPL)orWaldenstrom macroglobulinemia(WM).Flow cytometry supported this view;however,the immunohistochemical results of the lymph nodes overturned theabove diagnosis,and the patient was eventually diagnosed with MCD subtypeDLBCL.The presence of a monoclonal IgM component in the serum and infiltrationof small lymphocytes with a phenotype compatible with WM into the bonemarrow led us to propose a hypothesis that the case we report may have transformedfrom LPL/WM.CONCLUSIONThis highlights the possible transformation from WM to DLBCL,CD79B mutationmay be a potential biomarker for predicting this conversion.展开更多
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 onl...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.展开更多
BACKGROUND Multiple primary carcinoma(MPC)refers to two or more types of primary malignant tumors occurring simultaneously or sequentially in the same patient.Breast cancer is one of the most common malignant tumors a...BACKGROUND Multiple primary carcinoma(MPC)refers to two or more types of primary malignant tumors occurring simultaneously or sequentially in the same patient.Breast cancer is one of the most common malignant tumors affecting women.On the other hand,diffuse large B-cell lymphoma(DLBCL)is the most frequent form of non-Hodgkin’s lymphoma(NHL).In clinical practice,the simultaneous existence of metachronous primary breast cancer and lymphoma is rare.In this case,we highlight the significance of multidisciplinary management and advanced imaging techniques in the early identification and treatment of MPC cases.CASE SUMMARY In this study,we report a case of a 40-year-old female who was diagnosed with invasive ductal carcinoma of the breast(T3N1M0 stage IIIA LuminalB type)as the first primary cancer and DLBCL(stage IIIA)as the second primary cancer.The patient underwent the modified radical mastectomy for left breast cancer and received Rituximab,cyclophospha-mide,hydroxydaunorubicin,Oncovin(vincristine)and prednisolone regimen chemotherapy treatment for DLBCL.As of now,the patient is in stable condition.The successful diagnosis of the present patient highlights the need for multidisciplinary management and adoption of advanced imaging techniques to identify the second primary cancer,especially NHL.CONCLUSION Accurate diagnosis and management of metachronous MPC requires an interdisciplinary team and selection of an appropriate treatment plan.展开更多
Primary hepatic lymphoma is extremely rare,and only a few cases have been described on positron emission tomography(PET) or PET/computed tomography(PET/CT) imaging in the English literature.We report a case of a 55-ye...Primary hepatic lymphoma is extremely rare,and only a few cases have been described on positron emission tomography(PET) or PET/computed tomography(PET/CT) imaging in the English literature.We report a case of a 55-year-old woman who presented with low-grade fever and weight loss of three months.On CT scanning,a mass was identified which appeared to be a hypoattenuating lesion,on ultrasonographic imaging,the mass was hypoechoic,therefore,liver abscess or hepatic metastasis from a gastrointestinal primary was initially suspected.Tumor markers such as alpha-fetoprotein,carcinoembryonic antigen and carbohydrate antigen 19-9 were within normal limits.PET/CT demonstrated a large abnormal ring-like hypermetabolic focus in the right liver lobe.The lesion was resected and the histo-pathological findings were consistent with lymphoma.The patient was discharged two weeks after surgery and did not receive any further treatment.After 25 mo follow-up,she is in good health.18F-fluorodeoxyglucose PET/CT is useful in confirming the diagnosis of primary hepatic lymphoma by demonstrating no other foci with high uptake in other parts of the body.展开更多
<span style="font-family:""><span style="font-family:Verdana;">Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1% - 2% of all cardiac tumors. Due to their scarc...<span style="font-family:""><span style="font-family:Verdana;">Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1% - 2% of all cardiac tumors. Due to their scarcity and variable clinical presentation, early diagnosis is challenging. In this series, three cases of PCL from a single institution are described, which highlight the spectrum of presenting features and emphasize common principles. In the first case, a 73-year-old male who presented with dyspnea was found to have a 12.1 cm mass in the right ventricle. Biopsy via cardiac catheterization revealed diffuse large B cell ly</span><span style="font-family:Verdana;">mphoma (DLBCL). He was treated with chemoimmunotherapy and s</span><span style="font-family:Verdana;">urvived for two months. The second case describes a 55-year-old female who presented with chest pain. Imaging revealed a 3.1 cm right atrial mass and bilateral pleural effusions, with cytology from the latter demonstrating DLBCL. She was lost to follow up after three cycles of chemoimmunotherapy. In the last case, an 80-year-old female presented with weakness. A 4.0 cm mass was discovered in the right atrium and the patient expired shortly after admission. Autopsy confirmed the diagnosis of DLBCL. These case summaries are follo</span><span style="font-family:Verdana;">wed by a review of the clinical presentation, diagnostic approach, an</span><span style="font-family:Verdana;">d treatment outcomes of PCL.展开更多
Improving the outcome of relapsed or refractory diffuse large B-cell lymphoma(R/R DLBCL)remained an unmet need.The aim of this single-center,phase 2 trial was to evaluate the efficacy and safety of genetic subtype-gui...Improving the outcome of relapsed or refractory diffuse large B-cell lymphoma(R/R DLBCL)remained an unmet need.The aim of this single-center,phase 2 trial was to evaluate the efficacy and safety of genetic subtype-guided immunochemotherapy(R-ICE-X)in patients with R/R DLBCL:R-ICE-zanubrutinib for MCD-like and BN2-like,R-ICE-lenalidomide for N1-like and NOS,R-ICE-decitabine for TP53^(Mut),R-ICE-chidamide for EZB-like,and R-ICE-tofacitinib for ST2-like subtype.Enrolled patients were treated with assigned regimens for three cycles,and then responders were treated with autologous hematopoietic stem cell transplantation(ASCT)or 3 cycles of R-ICE-X consolidation and lenalidomide maintenance.The primary endpoint was the complete response(CR)rate.展开更多
To the Editor:Autologous CD19 chimeric antigen receptor(CAR)T-cell therapy has emerged as a crucial treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma(r/r DLBCL).[1]While CAR-T-cel...To the Editor:Autologous CD19 chimeric antigen receptor(CAR)T-cell therapy has emerged as a crucial treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma(r/r DLBCL).[1]While CAR-T-cell therapy has the potential for curing a subset of patients despite its high cost,over 60%of recipients eventually experience relapse.[2]This troubling statistic has led several clinical centers to investigate the underlying reasons for CAR-T-cell therapy failure or suboptimal outcomes.[3,4]Currently,a reliable method for predicting the curative efficacy of CAR-T cells is lacking.[5]In this study,we conducted a comprehensive analysis to identify various predictors influencing the success of CAR-T-cell therapy.Our efforts have culminated in the development of a predictive model designed to assess the therapeutic efficacy of CAR-T-cell therapy.展开更多
Background:Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T(CAR-T)cell therapy,underscoring the need for a detailed investigati...Background:Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T(CAR-T)cell therapy,underscoring the need for a detailed investigation.Given the limited variety of secondary tumor types reported to date,a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation.This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy,to clarify its pathogenesis and potential therapeutic targets.Methods:In this study,the bone marrow(BM)samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment.The CD45+BM cells were enriched with human CD45 microbeads.The CD45+cells were then sent for 10×genomics single-cell RNA sequencing(scRNA-seq)to identify cell populations.The Cell Ranger pipeline and CellChat were used for detailed analysis.Results:In this study,a rare type of secondary chronic myelomonocytic leukemia(CMML)were reported in a patient with diffuse large B-cell lymphoma(DLBCL)who had previously received CD19 CAR-T therapy.The scRNA-seq analysis revealed increased inflammatory cytokines,chemokines,and an immunosuppressive state of monocytes/macrophages,which may impair cytotoxic activity in both T and natural killer(NK)cells in secondary CMML before treatment.In contrast,their cytotoxicity was restored in secondary CMML after treatment.Conclusions:This finding delineates a previously unrecognized type of secondary tumor,CMML,after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy.In addition,the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.展开更多
To the Editor:Approximately 30–50%of diffuse large B-cell lymphoma(DLBCL)patients experience disease progression or relapse after chimeric antigen receptor T(CAR-T)cell therapy,and combination therapy may be a feasib...To the Editor:Approximately 30–50%of diffuse large B-cell lymphoma(DLBCL)patients experience disease progression or relapse after chimeric antigen receptor T(CAR-T)cell therapy,and combination therapy may be a feasible strategy to reduce the risk of relapse.Malignant B cells maintain B-cell receptor(BCR)expression on the cell surface and benefit from the proliferation,survival,and migration pathways triggered by BCR.Bruton tyrosine kinase(BTK)is an important component of the BCR signaling pathway,and the anti-lymphoma function generated by inhibiting the BTK pathway makes it a promising therapeutic target in B-cell malignant tumors and inflammatory diseases.展开更多
Background： Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone （CHOP） significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-c...Background： Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone （CHOP） significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma （DLBCL）. But relapse and refractory DLBC L occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL. Methods： We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled. Results： Seven trials including 1470 DLBCL patients were included in this systematic review and recta-analysis. Patients treated with maintenance rituximab have better overall survival （OS） and event-tree survival （EFS） than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI （0.55-0.94）, P - 0.02], progression-free survival （PFS） [HR - 0.61,95% CI（0.52-0.72）, P 〈 0.05], odds ratio （OR） [RR = 1.26, 95% CI（1.07-1,47）, P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = （ 1.14 - 1.65） P =0.001 ]. Conclusions： After first-line chemotherapy, the two rituximab-combined treatment strategies, including maintenance and salvage therapies can bring survival benefit. But due to the few studies, the low methodological quality assessment and the low outcome evidence quality, it＇s not confirmed that the two strategies are better than normal chemotherapy regimens. More high-quality randomized controlled trials are still needed to provide reliable evidence. The higher rate of infections after rituximab therapy should be taken into consideration when making treatment decisions.展开更多
To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel r...To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been developed.For optimal performance,they require the fragment ion spectra of targeted peptides as prior knowledge.In this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples.To build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker.We then applied the workflow to generate DPHL,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer samples.This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)patients.Thereafter,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated.As a second application,the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DLBCL)patients and 18 healthy control subjects.Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM.These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery.DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.展开更多
Anti-CD19 chimeric antigen receptor(CAR)-T cell therapy has achieved 40%–50%long-term complete response in relapsed or refractory diffuse large B-cell lymphoma(DLBCL)patients.However,the underlying mechanism of alter...Anti-CD19 chimeric antigen receptor(CAR)-T cell therapy has achieved 40%–50%long-term complete response in relapsed or refractory diffuse large B-cell lymphoma(DLBCL)patients.However,the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation.A multi-center phase I/II trial of anti-CD19 CD28z CAR-T(FKC876,ChiCTR1800019661)was conducted.Among 22 evaluable DLBCL patients,seven achieved complete remission,10 experienced partial remissions,while four had stable disease by day 29.Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients,and compared at different stages of treatment.M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells,leading to CAR-T cell therapy failure and disease progression in DLBCL.Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy,during both cell expansion and disease progression,which could not be altered by infiltrating CAR-T cells.Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments.Thus,our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.展开更多
基金supported by funding from the National Natural Science Foundation of China(Grant No.82170167 to Xiaoxi Zhou and Grant No.82300226 to Hui Luo)。
文摘CD5-positive(CD5+)diffuse large B-cell lymphoma(DLBCL)represents a special subgroup of DLBCL with a more aggressive disease course and is more likely to develop into relapsed/refractory(r/r)DLBCL in response to immunochemotherapy.The incidence of CD5+DLBCL is 5%–10%among DLBCL patients1.
基金sponsored by Shanghai Roche Pharmaceuticals Ltd.
文摘Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin’s lymphoma(NHL)worldwide,accounts for 39% and 44% of nodal and extranodal NHL cases in China,respectively1.Standard first-line treatment for DLBCL is chemo-immunotherapy with rituximab,cyclophos-phamide,doxorubicin,vincristine,and prednisone,which cures 50%-60% of patients2.
文摘AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[scheduled as cyclophosphamide,doxorubicin,vincristine and prednisone (CHOP)and CHOP-like],and chemotherapy combined with rituximab(group B,n=30).The primary end point of the study was complete response(CR)rate;the secondary end points were disease-free survival (DFS)at 5 years and overall survival(OS).RESULTS:Median follow-up was 62 mo(range:31102 mo).We observed a significant difference between the two groups(A vs B)in terms of CR[76.6%(23/30) vs 100%,P=0.04)and DFS at 5 years[73.3%(22/30) vs 100%,P=0.03).To date,19 group A(63.3%) patients are alive and 11 have died,while all group B patients are alive.No significant differences in toxicity were observed between the two groups.CONCLUSION:Rituximab in combination with chemotherapy improves CR rate,DFS and OS.Further prospective trials are needed to confirm our results.
基金supported by the National Natural Science Foundation of China(81372883,81001052)Natural Science Foundation of Guangdong Province,China(2015A030313020 and 8151008901000043)+3 种基金Science and Technology Planning Project of Guangdong Province,China(2011B031800222)Young Talents Key Project of Sun Yat?sen University(2015ykzd13,to Qing-qing Cai)Young Talents Project of Sun Yat-sen University(11ykpy56,to Qing-qing Cai)the Sister Institution Network Fund of MD Anderson Cancer Center(to Qing-qing Cai and Hui-Rao)
文摘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.
基金supported by the Shandong Provincial Natural Science Foundation of China(ZR2019MH096).
文摘Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess the antitumor effect of DHA on diffuse large B cell lymphoma cells and to determine the potential underlying mechanisms of DHA-induced cell apoptosis.Methods:Here,the Cell Counting Kit 8 assay was conducted to study cell proliferation.We performed Annexin V-FITC/propidium iodide staining,real-time polymerase chain reaction,and western blot analysis to analyze cell apoptosis and potential molecular mechanisms.Results:The results showed that DHA substantially suppressed cell proliferation and induced cell apoptosis in vitro in a time-and concentration-dependent fashion.Moreover,STAT3 activity could be inhibited after stimulation with DHA.Conclusion:These results imply that the underlying anti-tumoral effect of DHA may increase apoptosis in diffuse large B cell lymphoma cells via the STAT3 signaling pathway.In addition,DHA might be an effective drug for diffuse large B cell lymphoma therapy.
文摘Objective： We studied the diagnosis and therapy of primary lung diffuse large B cell lymphoma （DLBCL）. Methods： Analysis the clinical manifestations, pathologic character and immunohistochemical character of one lung diffuse B cell lymphoma patent. Results： In visual observation, it＇s a gray irregular fobulated mass, section was gray, fish-like, and number of necrotic foci. Observed under the microscope, subepithelial respiratory center oocyte-like cells diffuse proliferative, infiltration in lung tissue. Immunohistochemistry： CD20 （＋）, CD79a （＋）, CD3 （-）, CD45RO （-）, PCK （-）. Conclusion： Diffuse large B cell lymphoma is the most common subtype in non-Hodgkin lymphoma, but the primary lung diffuse large B cell lymphoma is rare. This disease is lack of typical clinical manifestations, so easily misdiagnosed. The diagnosis of diffuse large B cell lymphoma should be based on pathology and immunohistochemistry.
文摘BACKGROUND Central nervous system(CNS)lesions and peripheral neuropathy are rare among patients with non-Hodgkin’s lymphoma(NHL).Lymphomatous infiltration or local oppression usually accounts for CNS or peripheral nerve lesions.The incidence of peripheral neuropathy was 5%.Guillain-Barrésyndrome(GBS)is rare and may occur in less than 0.3%of patients with NHL.Hemophagocytic syndrome(HPS)is a rare complication of NHL.It has been reported that 1%of patients with hematological malignancies develop HPS.Diffuse large B-cell lymphoma(DLBCL)combined with GBS has been reported in 10 cases.CASE SUMMARY We report the case of a 53-year-old man who was initially hospitalized because of abnormal feelings in the lower limbs and urinary incontinence.He was finally diagnosed with DLBCL combined with GBS and HPS after 16 d,which was earlier than previously reported.Immunoglobulin pulse therapy,dexamethasone,and etoposide were immediately administered.The neurological symptoms did not improve,but cytopenia was relieved.However,GBS-related clinical symptoms were relieved partially after one cycle of rituximab-cyclophosphamide,hydroxydaunorubicin,vincristine,and prednisone(R-CHOP)chemotherapy and disappeared after six cycles of R-CHOP.CONCLUSION GBS and HPS heralding the diagnosis of Epstein-Barr virus DLBCL are rare.Herein,we report a rare case of DLBCL combined with GBS and HPS,and share our clinical experience.Traditional therapies may be effective if GBS occurs before lymphoma is diagnosed.Rapid diagnosis and treatment of DLBCL are crucial.
文摘BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common type of malignant lymphoma(ML),accounting for 30%-40%of cases of non-Hodgkin’s lymphoma(NHL)in adults.Primary paranasal sinus lymphoma is a rare presentation of extranodal NHL that accounts for only 0.17%of all lymphomas.ML from the maxillary sinus(MS)is a particularly rare presentation,and is thus often difficult to diagnose.We have reported the first known case of DLBCL originating from the MS with rapidly occurrent multiple skin metastasis.CASE SUMMARY An 81-year-old Japanese man visited our hospital due to continuous pain for 12 d in the left maxillary nerve area.His medical history included splenectomy due to a traffic injury,an old right cerebral infarction from when he was 74-years-old,hypertension,and type 2 diabetes mellitus.A plain head computed tomography(CT)scan revealed a 3 cm×3.1 cm×3 cm sized left MS.On day 25,left diplopia and ptosis occurred,and a follow-up CT on day 31 revealed the growth of the left MS mass.Based on an MS biopsy on day 50,we established a definitive diagnosis of DLBCL,non-germinal center B-cell-like originating from the left MS.The patient was admitted on day 62 due to rapid deterioration of his condition,and a plain CT scan revealed the further growth of the left MS mass,as well as multiple systemic metastasis,including of the skin.A skin biopsy on day 70 was found to be the same as that of the left MS mass.We notified the patient and his family of the disease,and they opted for palliative care,considering on his condition and age.The patient died on day 80.CONCLUSION This case suggests the need for careful,detailed examination,and for careful follow-up,when encountering patients presenting with a mass.
文摘BACKGROUNDOver the past 20 years,we have gained a deep understanding of the biologicalheterogeneity of diffuse large B cell lymphoma(DLBCL)and have developed arange of new treatment programs based on the characteristics of the disease,bringing us to the era of immune-chemotherapy.However,the effectiveness andmolecular mechanisms of targeted-immunotherapy remain unclear in DLBCL.Targeted-immunotherapy may be beneficial for specific subgroups of patients,thus requiring biomarker assessment.CASE SUMMARYHere,we report a case of MCD subtype DLBCL with MYD88L265P and CD79Bmutations,considered in the initial stage as lymphoplasmic lymphoma(LPL)orWaldenstrom macroglobulinemia(WM).Flow cytometry supported this view;however,the immunohistochemical results of the lymph nodes overturned theabove diagnosis,and the patient was eventually diagnosed with MCD subtypeDLBCL.The presence of a monoclonal IgM component in the serum and infiltrationof small lymphocytes with a phenotype compatible with WM into the bonemarrow led us to propose a hypothesis that the case we report may have transformedfrom LPL/WM.CONCLUSIONThis highlights the possible transformation from WM to DLBCL,CD79B mutationmay be a potential biomarker for predicting this conversion.
文摘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.
文摘BACKGROUND Multiple primary carcinoma(MPC)refers to two or more types of primary malignant tumors occurring simultaneously or sequentially in the same patient.Breast cancer is one of the most common malignant tumors affecting women.On the other hand,diffuse large B-cell lymphoma(DLBCL)is the most frequent form of non-Hodgkin’s lymphoma(NHL).In clinical practice,the simultaneous existence of metachronous primary breast cancer and lymphoma is rare.In this case,we highlight the significance of multidisciplinary management and advanced imaging techniques in the early identification and treatment of MPC cases.CASE SUMMARY In this study,we report a case of a 40-year-old female who was diagnosed with invasive ductal carcinoma of the breast(T3N1M0 stage IIIA LuminalB type)as the first primary cancer and DLBCL(stage IIIA)as the second primary cancer.The patient underwent the modified radical mastectomy for left breast cancer and received Rituximab,cyclophospha-mide,hydroxydaunorubicin,Oncovin(vincristine)and prednisolone regimen chemotherapy treatment for DLBCL.As of now,the patient is in stable condition.The successful diagnosis of the present patient highlights the need for multidisciplinary management and adoption of advanced imaging techniques to identify the second primary cancer,especially NHL.CONCLUSION Accurate diagnosis and management of metachronous MPC requires an interdisciplinary team and selection of an appropriate treatment plan.
文摘Primary hepatic lymphoma is extremely rare,and only a few cases have been described on positron emission tomography(PET) or PET/computed tomography(PET/CT) imaging in the English literature.We report a case of a 55-year-old woman who presented with low-grade fever and weight loss of three months.On CT scanning,a mass was identified which appeared to be a hypoattenuating lesion,on ultrasonographic imaging,the mass was hypoechoic,therefore,liver abscess or hepatic metastasis from a gastrointestinal primary was initially suspected.Tumor markers such as alpha-fetoprotein,carcinoembryonic antigen and carbohydrate antigen 19-9 were within normal limits.PET/CT demonstrated a large abnormal ring-like hypermetabolic focus in the right liver lobe.The lesion was resected and the histo-pathological findings were consistent with lymphoma.The patient was discharged two weeks after surgery and did not receive any further treatment.After 25 mo follow-up,she is in good health.18F-fluorodeoxyglucose PET/CT is useful in confirming the diagnosis of primary hepatic lymphoma by demonstrating no other foci with high uptake in other parts of the body.
文摘<span style="font-family:""><span style="font-family:Verdana;">Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1% - 2% of all cardiac tumors. Due to their scarcity and variable clinical presentation, early diagnosis is challenging. In this series, three cases of PCL from a single institution are described, which highlight the spectrum of presenting features and emphasize common principles. In the first case, a 73-year-old male who presented with dyspnea was found to have a 12.1 cm mass in the right ventricle. Biopsy via cardiac catheterization revealed diffuse large B cell ly</span><span style="font-family:Verdana;">mphoma (DLBCL). He was treated with chemoimmunotherapy and s</span><span style="font-family:Verdana;">urvived for two months. The second case describes a 55-year-old female who presented with chest pain. Imaging revealed a 3.1 cm right atrial mass and bilateral pleural effusions, with cytology from the latter demonstrating DLBCL. She was lost to follow up after three cycles of chemoimmunotherapy. In the last case, an 80-year-old female presented with weakness. A 4.0 cm mass was discovered in the right atrium and the patient expired shortly after admission. Autopsy confirmed the diagnosis of DLBCL. These case summaries are follo</span><span style="font-family:Verdana;">wed by a review of the clinical presentation, diagnostic approach, an</span><span style="font-family:Verdana;">d treatment outcomes of PCL.
基金supported by research funding from the National Key R&D Program of China(2023YFC3605704,2022YFC2502600)the National Natural Science Foundation of China(82130004,82170178,82200201,82070204)+6 种基金the Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine(DLY201601)the Chang Jiang Scholars Program,the Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1032B)Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(20152206,20152208)the Multicenter Hematology-Oncology Program Evaluation System(M-HOPES)the Shanghai Sailing Program(23YF1423700)the Collaborative Innovation Center of Systems Biomedicinethe Samuel Waxman Cancer Research Foundation.
文摘Improving the outcome of relapsed or refractory diffuse large B-cell lymphoma(R/R DLBCL)remained an unmet need.The aim of this single-center,phase 2 trial was to evaluate the efficacy and safety of genetic subtype-guided immunochemotherapy(R-ICE-X)in patients with R/R DLBCL:R-ICE-zanubrutinib for MCD-like and BN2-like,R-ICE-lenalidomide for N1-like and NOS,R-ICE-decitabine for TP53^(Mut),R-ICE-chidamide for EZB-like,and R-ICE-tofacitinib for ST2-like subtype.Enrolled patients were treated with assigned regimens for three cycles,and then responders were treated with autologous hematopoietic stem cell transplantation(ASCT)or 3 cycles of R-ICE-X consolidation and lenalidomide maintenance.The primary endpoint was the complete response(CR)rate.
基金supported by grants from the National Key R&D Program of China(No.2021YFA1100800)National Natural Science Foundation of China(Nos.81830004 and 82070168)+2 种基金Translational Research Grant of NCRCH(No.2020ZKZC04)Shanghai Municipal Health Commission(No.2020CXJQ02)Cultivation project of National Natural Science Foundation of Shanghai Tongji Hospital(No.GJPY2332).
文摘To the Editor:Autologous CD19 chimeric antigen receptor(CAR)T-cell therapy has emerged as a crucial treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma(r/r DLBCL).[1]While CAR-T-cell therapy has the potential for curing a subset of patients despite its high cost,over 60%of recipients eventually experience relapse.[2]This troubling statistic has led several clinical centers to investigate the underlying reasons for CAR-T-cell therapy failure or suboptimal outcomes.[3,4]Currently,a reliable method for predicting the curative efficacy of CAR-T cells is lacking.[5]In this study,we conducted a comprehensive analysis to identify various predictors influencing the success of CAR-T-cell therapy.Our efforts have culminated in the development of a predictive model designed to assess the therapeutic efficacy of CAR-T-cell therapy.
基金This work was supported by the National Natural Science Foundation of China(Nos.82370144,82270149,82170211,32100698,82270141,82370219,82000163,and 82200190)Henan Province Medical Science and Technology Research Project(Nos.SBGJ202101007,LHGJ20220305,LHGJ20220301,LHGJ20200366,SBGJ202102146,and SBGJ202102063)+4 种基金the National Natural Science Foundation of Henan Province(Nos.222300420068,242300421080,222300420333,and 222300420567)Key Research Projects of Henan Higher Education Institutions(No.222102310204)International Science and Technology Cooperation Program of Henan Provincial Science and Technology Department(No.232102521027)Leading Talent Project of Henan Province(No.LJRC2023004)Funding for the Scientific Research and Innovation Team of the First Affiliated Hospital of Zhengzhou University.
文摘Background:Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T(CAR-T)cell therapy,underscoring the need for a detailed investigation.Given the limited variety of secondary tumor types reported to date,a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation.This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy,to clarify its pathogenesis and potential therapeutic targets.Methods:In this study,the bone marrow(BM)samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment.The CD45+BM cells were enriched with human CD45 microbeads.The CD45+cells were then sent for 10×genomics single-cell RNA sequencing(scRNA-seq)to identify cell populations.The Cell Ranger pipeline and CellChat were used for detailed analysis.Results:In this study,a rare type of secondary chronic myelomonocytic leukemia(CMML)were reported in a patient with diffuse large B-cell lymphoma(DLBCL)who had previously received CD19 CAR-T therapy.The scRNA-seq analysis revealed increased inflammatory cytokines,chemokines,and an immunosuppressive state of monocytes/macrophages,which may impair cytotoxic activity in both T and natural killer(NK)cells in secondary CMML before treatment.In contrast,their cytotoxicity was restored in secondary CMML after treatment.Conclusions:This finding delineates a previously unrecognized type of secondary tumor,CMML,after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy.In addition,the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
文摘To the Editor:Approximately 30–50%of diffuse large B-cell lymphoma(DLBCL)patients experience disease progression or relapse after chimeric antigen receptor T(CAR-T)cell therapy,and combination therapy may be a feasible strategy to reduce the risk of relapse.Malignant B cells maintain B-cell receptor(BCR)expression on the cell surface and benefit from the proliferation,survival,and migration pathways triggered by BCR.Bruton tyrosine kinase(BTK)is an important component of the BCR signaling pathway,and the anti-lymphoma function generated by inhibiting the BTK pathway makes it a promising therapeutic target in B-cell malignant tumors and inflammatory diseases.
文摘Background： Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone （CHOP） significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma （DLBCL）. But relapse and refractory DLBC L occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL. Methods： We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled. Results： Seven trials including 1470 DLBCL patients were included in this systematic review and recta-analysis. Patients treated with maintenance rituximab have better overall survival （OS） and event-tree survival （EFS） than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI （0.55-0.94）, P - 0.02], progression-free survival （PFS） [HR - 0.61,95% CI（0.52-0.72）, P 〈 0.05], odds ratio （OR） [RR = 1.26, 95% CI（1.07-1,47）, P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = （ 1.14 - 1.65） P =0.001 ]. Conclusions： After first-line chemotherapy, the two rituximab-combined treatment strategies, including maintenance and salvage therapies can bring survival benefit. But due to the few studies, the low methodological quality assessment and the low outcome evidence quality, it＇s not confirmed that the two strategies are better than normal chemotherapy regimens. More high-quality randomized controlled trials are still needed to provide reliable evidence. The higher rate of infections after rituximab therapy should be taken into consideration when making treatment decisions.
基金supported by the National Natural Science Foundation of China(Grant No.81972492)National Science Fund for Young Scholars(Grant No.21904107)+7 种基金Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(Grant No.LR19C050001)Hangzhou Agriculture and Society Advancement Program(Grant No.20190101A04)Westlake Startup Grantresearch funds from the National Cancer Centre Singapore and Singapore General Hospital,Singaporethe National Key R&D Program of China(Grant No.2016YFC0901704)Zhejiang Innovation Discipline Project of Laboratory Animal Genetic Engineering(Grant No.201510)the Netherlands Cancer Society(Grant No.NKI 2014-6651)The Netherlands Organization for Scientific Research(NWO)-Middelgroot(Grant No.91116017)
文摘To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been developed.For optimal performance,they require the fragment ion spectra of targeted peptides as prior knowledge.In this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples.To build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker.We then applied the workflow to generate DPHL,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer samples.This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)patients.Thereafter,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated.As a second application,the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DLBCL)patients and 18 healthy control subjects.Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM.These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery.DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.
基金the National Natural Science Foundation of China(Nos.81830007,82130004,81600155,and 81670716)Clinical Research Plan of SHDC(No.2020CR1032B),Shanghai Rising-Star Program(No.19QA145600)+5 种基金Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai(No.2017YQ075)Talent(Class A)of Guangci Excellence Youth Plan(No.GCQN-2019-A16)Clinical Research Plan of Shanghai Hospital Development Center(No.SHDC2020CR1032B)Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(Nos.20152206 and 20152208)China CAR-T Clinical Research Fund Project(No.CARTFR-05)Samuel Waxman Cancer Research Foundation.
文摘Anti-CD19 chimeric antigen receptor(CAR)-T cell therapy has achieved 40%–50%long-term complete response in relapsed or refractory diffuse large B-cell lymphoma(DLBCL)patients.However,the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation.A multi-center phase I/II trial of anti-CD19 CD28z CAR-T(FKC876,ChiCTR1800019661)was conducted.Among 22 evaluable DLBCL patients,seven achieved complete remission,10 experienced partial remissions,while four had stable disease by day 29.Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients,and compared at different stages of treatment.M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells,leading to CAR-T cell therapy failure and disease progression in DLBCL.Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy,during both cell expansion and disease progression,which could not be altered by infiltrating CAR-T cells.Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments.Thus,our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.
