Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a cru...Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a crucial mechanism contributing to tumor drug resistance.Here,we analyzed SENEX/Rho GTPase Activating Protein 18(ARHGAP18)expression and prognostic significance in doxorubicin-induced B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL cell senescence and the effect of combining specific inhibitors on apoptosis resistance in B-NHL-TIS cells.Methods:Raji cells were transfected with the human SENEX shRNA recombinant lentiviral vector(Sh-SENEX)and the empty vector negative(NC)to construct a stable transfection cell line with knockdown of SENEX.Effect of SENEX-silencing on B-NHL-TIS formation,cell function and cell cycle-related pathways was analyzed.Using doxorubicin(DOX)-inducible senescent B-NHL cells combined with the specific cyclin dependent kinase 4/6(CDK4/6)inhibitor Palbociclib to observe that blocking CDK4/6 effects on TIS formation.SENEX expression of 21 B-NHL patients and 8 healthy controls were analyzed by qRT-PCR,and the correlation between its expression and clinical indicators were evaluated.Results:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting cell proliferation,collectively suppressing the formation of TIS in B-NHL.Blockade of CDK4/6 promotes the DOX-induced G1 phase arrest to enhance TIS formation in B-NHL cells which can reverse the regulatory effect of silencing SENEX on B-NHL cell cycle regulation and senescence.The expression levels of SENEX were notably elevated in B-NHL patients compared to healthy controls,and Elevated expression levels of SENEX were associated with poor prognosis of B-NHL patients.Conclusions:SENEX enhances apoptosis resistance in B-NHL by inhibiting CDK4/6,thereby preventing G1-S phase transition and promoting TIS formation.展开更多
Dear Editor,We present a rare case of a primary penile follicular center non-Hodgkin lymphoma and a review of the available literature on this condition.A BCL2 gene transposition which was identified with fluorescent ...Dear Editor,We present a rare case of a primary penile follicular center non-Hodgkin lymphoma and a review of the available literature on this condition.A BCL2 gene transposition which was identified with fluorescent in situ hybridization(FISH)molecular analysis is a unique manifestation not previously reported to the best of our knowledge.A 67-year-old man presented with a 3-month history of a small nodule on the left side of the corona of glans penis.The patient had no significant medical or family history.The patient underwent excision and biopsy of the penile lesion with a 0.5 cm macroscopic margin under local anesthesia and sedation.He was discharged on the day of surgery,and there were no postoperative complications or adverse events.The informed consent was obtained from thepatient.展开更多
Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-c...Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.展开更多
Objective This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma(NHL).Methods We compared the age-standardized incidence rate(ASIR),age-standard...Objective This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma(NHL).Methods We compared the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and the ASMR to ASIR ratio(MIR)at national and regional levels and studied the correlation between the MIR and the human development index(HDI)in 2012 and 2018.Results The highest ASIR was in North America in 2012 and in Australia in 2018,and the lowest ASIR was in Central and South Asia in both 2012 and 2018.The highest ASMR was in North Africa in both 2012 and 2018,and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018.The lowest MIR was in Australia in both 2012 and 2018,and the highest MIR was in Western Africa in both 2012 and 2018.HDI was strongly negatively correlated with MIR(r:−0.8810,P<0.0001,2012;r:−0.8895,P<0.0001,2018).Compared to the 2012 data,the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018.Conclusion The MIR is negatively correlated with HDI.Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.展开更多
Febrile cholestatic liver disease is an extremely unusual presentation of Hodgkin lymphoma(HL).The liver biopsy of a 40-year-old man with febrile episodes and cholestatic laboratory pattern disclosed an uncommon subty...Febrile cholestatic liver disease is an extremely unusual presentation of Hodgkin lymphoma(HL).The liver biopsy of a 40-year-old man with febrile episodes and cholestatic laboratory pattern disclosed an uncommon subtype of HL,a nodular lymphocyte-predominant HL(NLPHL).Liver involvement in the early stage of the usually indolent NLPHL's clinical course suggests an aggressiveness and unfavorable outcome.Emphasizing a liver biopsy early in the diagnostic algorithm enables accurate diagnosis and appropriate treatment.Although rare,HL should be considered in the differential diagnosis of cholestasis.展开更多
BACKGROUND Academic studies have proved that anti-programmed death-1(PD-1)monoclonal antibodies demonstrated remarkable activity in relapsed/refractory classical Hodgkin lymphoma(cHL).However,most patients ultimately ...BACKGROUND Academic studies have proved that anti-programmed death-1(PD-1)monoclonal antibodies demonstrated remarkable activity in relapsed/refractory classical Hodgkin lymphoma(cHL).However,most patients ultimately experienced failure or resistance.It is urgent and necessary to develop a novel strategy for relapsed/refractory cHL.The aim of this case report is to evaluate the combination approach of low-dose decitabine plus a PD-1 inhibitor in relapsed/refractory cHL patients with prior PD-1 inhibitor exposure.CASE SUMMARY The patient was a 27-year-old man who complained of enlarged right-sided cervical lymph nodes and progressive pain aggravation of the right shoulder over the past 3 mo before admission.Histological analysis of lymph node biopsy was suggestive of cHL.The patient experienced failure of eight lines of therapy,including multiple cycles of chemotherapy,PD-1 blockade,and anti-CD47 antibody therapy.Contrast-enhanced CT showed that the tumors of the chest and abdomen significantly shrunk or disappeared after three cycles of treatment with decitabine plus tislelizumab.The patient had been followed for 11.5 mo until March 2,2021,and no progressive enlargement of the tumor was observed.CONCLUSION The strategy of combining low-dose decitabine with tislelizumab could reverse the resistance to PD-1 inhibitors in patients with heavily pretreated relapsed/refractory cHL.The therapeutic effect of this strategy needs to be further assessed.展开更多
Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclon...Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.展开更多
BACKGROUND There are several case reports of acute cholecystitis as the initial presentation of lymphoma of the gallbladder;all reports describe non-Hodgkin lymphoma or its subtypes on histopathology of the gallbladde...BACKGROUND There are several case reports of acute cholecystitis as the initial presentation of lymphoma of the gallbladder;all reports describe non-Hodgkin lymphoma or its subtypes on histopathology of the gallbladder tissue itself.Interestingly,there is no description in the literature of Hodgkin lymphoma causing hilar lymphadenopathy,inevitably presenting as ruptured cholecystitis with imaging mimicking gallbladder adenocarcinoma.CASE SUMMARY A 48-year-old man with a past medical history of diabetes mellitus presented with progressive abdominal pain,jaundice,night sweats,weakness,and unintended weight loss for one month.Work-up revealed a mass in the region of the porta hepatis causing obstructions of the cystic and common hepatic ducts,gallbladder rupture,as well as retroperitoneal lymphadenopathy.The clinical picture and imaging findings were suspicious for locally advanced gallbladder adenocarcinoma causing ruptured cholecystitis and cholangitis,with metastases to retroperitoneal lymph nodes.Minimally invasive techniques,including endoscopic duct brushings and percutaneous lymph node biopsy,were inadequate for tissue diagnosis.Therefore,this case required exploratory laparo-tomy,open cholecystectomy,and periaortic lymph node dissection for histopathological assessment and definitive diagnosis.Hodgkin lymphoma was present in the lymph nodes while the gallbladder specimen had no evidence of malignancy.CONCLUSION This clinical scenario highlights the importance of histopathological assessment in diagnosing gallbladder malignancy in a patient with gallbladder perforation and a grossly positive positron emission tomography/computed tomography scan.For both gallbladder adenocarcinoma and Hodgkin lymphoma,medical and surgical therapies must be tailored to the specific disease entity in order to achieve optimal long-term survival rates.展开更多
BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)...BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.展开更多
Epstein Barr virus （EBV） positive mucocutaneous ulcers（EBVMCU） form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosu...Epstein Barr virus （EBV） positive mucocutaneous ulcers（EBVMCU） form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract （GIT）. Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. Wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn＇s disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn＇s disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.展开更多
This study aims to examine the levels of circulating endothelial progenitor cells (cEPCs) in the peripheral blood of patients with non-Hodgkin lymphoma (NHL) and their correlation with the tumor stage. Forty-one patie...This study aims to examine the levels of circulating endothelial progenitor cells (cEPCs) in the peripheral blood of patients with non-Hodgkin lymphoma (NHL) and their correlation with the tumor stage. Forty-one patients with biopsy-proven NHL and 16 healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation, and cEPCs were characterized by triple staining using antibodies against CD133, CD34 and vascular endothelial growth factor receptor-2 (VEGFR-2, CD309) and quantified by flow cytometry. In NHL patients, the number of cEPCs was significantly greater than in control group (P=0.000). The cEPCs counts in patients with NHL of stage Ⅲ-Ⅳ were significantly greater than in stage Ⅰ-Ⅱ (P=0.010). FACS analysis revealed that the number of cEPCs in NHL patients had no correlation with the gender (P=0.401) or the pathological category (P=0.852). It was suggested that the over-expression of cEPCs in NHL patients may serve as a novel biomarker for disease progression in NHL.展开更多
Objective: High-dose chemotherapy(HDC) followed by autologous stem cell transplantation(ASCT) is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma(NHL).Howev...Objective: High-dose chemotherapy(HDC) followed by autologous stem cell transplantation(ASCT) is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma(NHL).However,a proportion of patients do not respond to ASCT.^(18)F-fluorodeoxyglucose(FDG) positron emission tomography(PET)/computed tomography(CT) has been widely used for staging,response evaluation,and prognosis prediction.Here,we investigated the prognostic role of PET/CT in NHL patients before and after ASCT.Methods: A retrospective study was conducted at Peking University Cancer Hospital.All NHL patients who underwent ASCT between March 2010 and July 2016 were identified.Patients who had PET/CT scan before and after ASCT were included.Deauville criteria(5-point scale) were used to interpret PET scans.Univariate and multivariate survival analyses were performed using Cox regression.The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic(ROC) curve.Results: In total,79 patients were enrolled in this study.In univariate analysis,pre-and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival(PFS) and overall survival(OS).Patients with negative pre-ASCT PET result demonstrated significantly better PFS(84.2% vs.54.2%) and OS(89.2% vs.63.6%) than patients with positive pre-ASCT PET result.PFS(91.6% vs.25.3%) and OS(96.5% vs.36.8%) were also significantly different between patients with negative and positive post-ASCT PET result.Multivariate analysis also showed a significant association between survival and post-ASCT PET result.ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone.Combined pre-and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation.Deauville criteria score >3 was identified as the best cutoff value for post-ASCT PET.Conclusions: Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT.The prognostic significance can be improved when combining preASCT PET result with post-ASCT PET result.Deauville criteria can be used for interpreting PET scans in this scenario.展开更多
Although Epstein-Barr virus(EBV)is present in the malignant Hodgkin/Reed-Sternberg(HRS)cells of a proportion of cases of classical Hodgkin lymphoma(c HL),how the virus contributes to the pathogenesis of this disease r...Although Epstein-Barr virus(EBV)is present in the malignant Hodgkin/Reed-Sternberg(HRS)cells of a proportion of cases of classical Hodgkin lymphoma(c HL),how the virus contributes to the pathogenesis of this disease remains poorly defined.It is clear from the studies of other EBV-associated cancers that the virus is usually not sufficient for tumor development and that other oncogenic co-factors are required.This article reviews what is known about the contribution of EBV to the pathogenesis of c HL and focuses on emerging evidence implicating chronic inflammation as a potential oncogenic co-factor in this malignancy.展开更多
Objective: Although the prognostic value of programmed cell death-ligand 1(PD-L1) expression in non-Hodgkin lymphoma(NHL) has been evaluated in many studies, the results remain controversial. To investigate the progno...Objective: Although the prognostic value of programmed cell death-ligand 1(PD-L1) expression in non-Hodgkin lymphoma(NHL) has been evaluated in many studies, the results remain controversial. To investigate the prognostic role of PD-L1 expression and the association between PD-L1 expression and clinicopathological features of NHL, we performed a meta-analysis.Methods: The Pub Med, EMBASE, and Cochrane Library databases were searched up to November 30, 2017. The hazard ratio(HR), 95% confidence interval(CI), and odds ratios(OR) with 95% CIs were combined to evaluate the association of PD-L1 expression with overall survival(OS) and clinicopathological features. Review manager 5.3 and STATA 12.0 were used in this meta-analysis.Results: A total of 2,005 patients across nine studies were enrolled in our meta-analysis, and the pooled results showed that high PD-L1 expression was associated with a poor prognosis(HR=2.04, 95% CI: 1.18–3.54, P=0.01). In the subgroup analysis according to histology types, pooled results demonstrated that an increased PD-L1 expression was an unfavorable prognostic factor for diffuse large B-cell lymphoma(HR=1.92, 95% CI: 1.06–3.48, P=0.03) but not for natural killer/T-cell lymphoma(HR=2.41, 95%CI: 0.47–12.22, P=0.29). Pooled ORs indicated that PD-L1 expression was higher in NHL with international prognostic indices of≥3. However, PD-L1 expression had no correlation with gender, age, disease stage, lactate dehydrogenase level, B symptoms, and germinal center B-cell-like lymphoma.Conclusions: High PD-L1 expression was a poor prognostic biomarker in patients with NHL. Because of our limited sample size,high-quality studies with larger sample sizes are needed to validate our results.展开更多
At present,approximately 20%of Hodgkin lymphomas(HL)are relapsed and refractory,and therapeutic methods including chemotherapy,radiotherapy,and even stem cell transplantation are unsatisfactory.Brentuximab vedotin,com...At present,approximately 20%of Hodgkin lymphomas(HL)are relapsed and refractory,and therapeutic methods including chemotherapy,radiotherapy,and even stem cell transplantation are unsatisfactory.Brentuximab vedotin,composed of CD30 antibody and a chemotherapeutic agent,is a new targeted drug that eradicates tumor cells by binding to the CD30 antigen on their surface.In clinical trials,the response rate and complete remission rate of this drug were 73%and 40%,respectively,for relapsed and refractory HL.Here we report a case of CD30-positive relapsed and refractory HL that was treated with brentuximab.Before the treatment with brentuximab,the patient underwent chemotherapy,radiotherapy,and autologous stem cell transplantation.However,the disease continued to progress,affecting multiple organs and prompting symptoms such as persistent fever.After the treatment with brentuximab,the patient′s condition improved.Body temperature returned to normal after 4 days.Lung nodules were reduced in size and number after a single course of treatment,and PET/CT showed partial remission and complete remission after 3 and 6 courses of treatment,respectively.The entire treatment process progressed smoothly,though the patient experienced some symptoms due to chemotherapy,including peripheral neuritis of the limbs,irritating dry cough,and mild increase in aminotransferase.No serious adverse effects were observed.The current general condition of the patient is good;the continuous complete remission has amounted to 6 months.展开更多
In order to investigate the expression change of survivin in non-Hodgkin lymphoma (NHL) and its possible effects on NHL development, the expression of survivin, Ki-67, caspase3 and FVIIIRAg in reactive lymphoid hyperp...In order to investigate the expression change of survivin in non-Hodgkin lymphoma (NHL) and its possible effects on NHL development, the expression of survivin, Ki-67, caspase3 and FVIIIRAg in reactive lymphoid hyperplasia (RH) and NHL was detected by immunohistochemical assay, and apoptosis index (AI) in RH and NHL by TUNEL analysis. The results showed that the expression of survivin is significantly higher in aggressive NHL than in indolent NHL (P<0.01), while there was no statistically significant difference between RH and indolent NHL (P>0.05). The expression of survivin had a significantly positive correlation with the expression of Ki-67 and FVIIIRAg (r=0.6495, 0.6635, respectively, both P<0.01), and a negative correlation with the expression of cas-pase3 and AI (r=-0.5820, -0.6013, respectively, P<0.01). It was suggested that survivin may contribute to the progression of NHL by playing an important role in promoting cell proliferation, inhibiting cell apoptosis and enlisting angiogenesis. Survivin expression is closely related to malignant grade and therefore may be considered an important prognostic factor of NHL.展开更多
The relationship between angiogenesis and eukaryotic translation initiation factor 4E (EIF4E) expression level in non-Hodgkin lymphoma (NHL) was studied. Mean microvessel density (MVD) and EIF4E were detected in 52 ly...The relationship between angiogenesis and eukaryotic translation initiation factor 4E (EIF4E) expression level in non-Hodgkin lymphoma (NHL) was studied. Mean microvessel density (MVD) and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3.1 (+) and transfected into Raji cells. A series of angiogenesis related factors,including vascular endothelial growth factor (VEGF), matrix metalloproteinases 9 (MMP-9) and tissue inhibitor of metalloproteinases-2 (TIMP-2) proteins were detected by Western blot. The results showed that: (1) The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas(P<0.05)and the expression of EIF4E was positively correlated with MVD in lymph node of NHL(r=0.695, P<0.01). (2) Antisense EIF4E eukaryocytic expression vector (pcDNA3.1-EIF4Eas) was constructed successfully. (3) EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells (NHPMC), and blockage of EIF4E expression brought down the expression of VEGF and MMP-9. However, TIMP-2 was undetectable in Raji cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL.展开更多
Primary gastric lymphomas(PGLs)are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and molecularly.Their main histological types are diffuse large B-cell lymphoma(DLBCL)or mucosaa...Primary gastric lymphomas(PGLs)are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and molecularly.Their main histological types are diffuse large B-cell lymphoma(DLBCL)or mucosaassociated lymphoma tissue.PGL has been one of the main fields of clinical research of our group in recent years.Although gastric DLBCLs are frequent,sufficient data to guide optimal care are scarce.Until today,a multidisciplinary approach has been applied,including chemotherapy,surgery,radiotherapy or a combination of these treatments.In this minireview article,we provide an overview of the clinical manifestations,diagnosis and staging of these diseases,along with their molecular pathogenesis and the most important related clinical published series.We then discuss the scientific gaps,perils and pitfalls that exist regarding the aforementioned studies,in parallel with the unmet need for future research and comment on the proper methodology for such retrospective studies.Aiming to fill this gap,we retrospectively evaluated the trends in clinical presentation,management and outcome among 165 patients with DLBCL PGL who were seen in our institutions in 1980-2014.The study cohort was divided into two subgroups,comparing the main 2 therapeutic options[cyclophosphamide doxorubicin vincristine prednisone(CHOP)vs rituximab-CHOP(R-CHOP)].A better outcome with immunochemotherapy(R-CHOP)was observed.In the next 2 mo,we will present the update of our study with the same basic conclusion.展开更多
Background: Non-Hodgkin’s lymphoma is an aggressive malignant disease in children and adolescents. Although it is the fourth most common malignancy in Saudi children as reported in Saudi cancer registry, less informa...Background: Non-Hodgkin’s lymphoma is an aggressive malignant disease in children and adolescents. Although it is the fourth most common malignancy in Saudi children as reported in Saudi cancer registry, less information is available about pediatric Non-Hodgkin lymphoma and its outcome in Saudi Arabia. Study Objectives: To provide demographic data, disease characteristics, treatment protocol, toxicity and outcome of treatment in children & adolescents with Non-Hodgkin’s lymphoma treated at KFMC. This study will form base line for future studies about pediatric Non-Hodgkin’s lymphoma in KFMC, which may help to improve outcome for children with cancer in Saudi Arabia. Study Patients and Method: We retrospectively analyzed 28 children and adolescents diagnosed to have Non-Hodgkin’s lymphoma at KFMC between December 2006 and December 2013, followed-up through June 2014. Results: Of the 28 patients, 10 (35.7%) girls and 18 (64.3%) boys, the male-to-female ratio was 1.8;1. The median age at time of diagnosis was 6.4 years old (range 2.0 to 13.0 years old). The majority of patients (64.3%) were aged between 5 and 12 years old. Burkitt’s lymphoma BL/BLL was the most common pathological subtype (60.7%), and DLBCL was the second most common subtype (21.4%). Abdominal and Retroperitoneal involvement was the most common primary site (78.6%) including the ileocaecal region. Most of the children presented with advanced Stage III and IV (75%), Cytogenetic study which screens specifically for the t (8;14) (q24;q32) a characteristic genetic feature of Burkitt’s Lymphoma was obtained from 21 patients, variant rearrangement was observed in 3/21 samples and complex chromosomes karyotype in addition to IGH/MYC rearrangement was observed in 2/21 samples. Those patients presented with very aggressive lymphoma and combined BM and CNS involvement. We use the French-American-British Mature B-Cell Lymphoma 96 Protocol (FAB LMB 96) for treatment fornewly diagnosed Mature B-Cell type NHL and high risk ALL CCG 1961 Protocol for lymphoblastic lymphoma and international Anaplastic Large Cell Lymphoma 99 Study Protocol for ALCL. The median follow-up in patients not experiencing an adverse event was 53.1 months. The estimated 3-year EFE and OS rates in the entire cohort of patients with newly diagnosed NHL treated in the KFMC were 85.2% and 89.2% respectively;Overall survival (OS) rate of patients with mature B-cell-NHL was 88.9%. Conclusion: The outcomes and survival in our small series appeared to be excellent compared with those reported in other international trials even though most of our patients presented in advanced stage of the disease. We feel that the importance of the current study is to document the relative distribution of various types of pediatric non-Hodgkin’s lymphomas and age-specific distribution in different Histological subtypes.展开更多
The interaction between cluster of differentiation 47(CD47)and signal regulatory proteinα(SiRPa)protects healthy cells from macrophage attack,which is crucial for maintain-ing immune homeostasis.Overexpression of CD4...The interaction between cluster of differentiation 47(CD47)and signal regulatory proteinα(SiRPa)protects healthy cells from macrophage attack,which is crucial for maintain-ing immune homeostasis.Overexpression of CD47 occurs widely across various tumor cell types and transmits the"don't eat me"signal to macrophages to avoid phagocytosis through binding to SIRPa.Blockade of the CD47-SIRPa axis is therefore a promising approach for cancer treat-ment.Lymphoma is the most common hematological malignancy and is an area of unmet clin-ical need.This review mainly described the current strategies targeting the CD47-SIRPa axis,including antibodies,SiRPaFc fusion proteins,small molecule inhibitors,and peptides both in preclinical studies and clinical trials with Hodgkin lymphoma and non-Hodgkin lymphoma.展开更多
基金This work was supported by the Major Subject of Science and Technology of Anhui Province(Grant Number:201903a07020030).
文摘Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a crucial mechanism contributing to tumor drug resistance.Here,we analyzed SENEX/Rho GTPase Activating Protein 18(ARHGAP18)expression and prognostic significance in doxorubicin-induced B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL cell senescence and the effect of combining specific inhibitors on apoptosis resistance in B-NHL-TIS cells.Methods:Raji cells were transfected with the human SENEX shRNA recombinant lentiviral vector(Sh-SENEX)and the empty vector negative(NC)to construct a stable transfection cell line with knockdown of SENEX.Effect of SENEX-silencing on B-NHL-TIS formation,cell function and cell cycle-related pathways was analyzed.Using doxorubicin(DOX)-inducible senescent B-NHL cells combined with the specific cyclin dependent kinase 4/6(CDK4/6)inhibitor Palbociclib to observe that blocking CDK4/6 effects on TIS formation.SENEX expression of 21 B-NHL patients and 8 healthy controls were analyzed by qRT-PCR,and the correlation between its expression and clinical indicators were evaluated.Results:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting cell proliferation,collectively suppressing the formation of TIS in B-NHL.Blockade of CDK4/6 promotes the DOX-induced G1 phase arrest to enhance TIS formation in B-NHL cells which can reverse the regulatory effect of silencing SENEX on B-NHL cell cycle regulation and senescence.The expression levels of SENEX were notably elevated in B-NHL patients compared to healthy controls,and Elevated expression levels of SENEX were associated with poor prognosis of B-NHL patients.Conclusions:SENEX enhances apoptosis resistance in B-NHL by inhibiting CDK4/6,thereby preventing G1-S phase transition and promoting TIS formation.
文摘Dear Editor,We present a rare case of a primary penile follicular center non-Hodgkin lymphoma and a review of the available literature on this condition.A BCL2 gene transposition which was identified with fluorescent in situ hybridization(FISH)molecular analysis is a unique manifestation not previously reported to the best of our knowledge.A 67-year-old man presented with a 3-month history of a small nodule on the left side of the corona of glans penis.The patient had no significant medical or family history.The patient underwent excision and biopsy of the penile lesion with a 0.5 cm macroscopic margin under local anesthesia and sedation.He was discharged on the day of surgery,and there were no postoperative complications or adverse events.The informed consent was obtained from thepatient.
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.
基金supported by the National Natural Science Foundation of China(No.81700147).
文摘Objective This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma(NHL).Methods We compared the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and the ASMR to ASIR ratio(MIR)at national and regional levels and studied the correlation between the MIR and the human development index(HDI)in 2012 and 2018.Results The highest ASIR was in North America in 2012 and in Australia in 2018,and the lowest ASIR was in Central and South Asia in both 2012 and 2018.The highest ASMR was in North Africa in both 2012 and 2018,and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018.The lowest MIR was in Australia in both 2012 and 2018,and the highest MIR was in Western Africa in both 2012 and 2018.HDI was strongly negatively correlated with MIR(r:−0.8810,P<0.0001,2012;r:−0.8895,P<0.0001,2018).Compared to the 2012 data,the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018.Conclusion The MIR is negatively correlated with HDI.Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.
文摘Febrile cholestatic liver disease is an extremely unusual presentation of Hodgkin lymphoma(HL).The liver biopsy of a 40-year-old man with febrile episodes and cholestatic laboratory pattern disclosed an uncommon subtype of HL,a nodular lymphocyte-predominant HL(NLPHL).Liver involvement in the early stage of the usually indolent NLPHL's clinical course suggests an aggressiveness and unfavorable outcome.Emphasizing a liver biopsy early in the diagnostic algorithm enables accurate diagnosis and appropriate treatment.Although rare,HL should be considered in the differential diagnosis of cholestasis.
文摘BACKGROUND Academic studies have proved that anti-programmed death-1(PD-1)monoclonal antibodies demonstrated remarkable activity in relapsed/refractory classical Hodgkin lymphoma(cHL).However,most patients ultimately experienced failure or resistance.It is urgent and necessary to develop a novel strategy for relapsed/refractory cHL.The aim of this case report is to evaluate the combination approach of low-dose decitabine plus a PD-1 inhibitor in relapsed/refractory cHL patients with prior PD-1 inhibitor exposure.CASE SUMMARY The patient was a 27-year-old man who complained of enlarged right-sided cervical lymph nodes and progressive pain aggravation of the right shoulder over the past 3 mo before admission.Histological analysis of lymph node biopsy was suggestive of cHL.The patient experienced failure of eight lines of therapy,including multiple cycles of chemotherapy,PD-1 blockade,and anti-CD47 antibody therapy.Contrast-enhanced CT showed that the tumors of the chest and abdomen significantly shrunk or disappeared after three cycles of treatment with decitabine plus tislelizumab.The patient had been followed for 11.5 mo until March 2,2021,and no progressive enlargement of the tumor was observed.CONCLUSION The strategy of combining low-dose decitabine with tislelizumab could reverse the resistance to PD-1 inhibitors in patients with heavily pretreated relapsed/refractory cHL.The therapeutic effect of this strategy needs to be further assessed.
基金funded by Sinocelltech Ltd, Beijing Chinapartly supported by China National Major Project for New Drug Innovation (No. 2012ZX09303012 and No. 2017ZX09304015)
文摘Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.
文摘BACKGROUND There are several case reports of acute cholecystitis as the initial presentation of lymphoma of the gallbladder;all reports describe non-Hodgkin lymphoma or its subtypes on histopathology of the gallbladder tissue itself.Interestingly,there is no description in the literature of Hodgkin lymphoma causing hilar lymphadenopathy,inevitably presenting as ruptured cholecystitis with imaging mimicking gallbladder adenocarcinoma.CASE SUMMARY A 48-year-old man with a past medical history of diabetes mellitus presented with progressive abdominal pain,jaundice,night sweats,weakness,and unintended weight loss for one month.Work-up revealed a mass in the region of the porta hepatis causing obstructions of the cystic and common hepatic ducts,gallbladder rupture,as well as retroperitoneal lymphadenopathy.The clinical picture and imaging findings were suspicious for locally advanced gallbladder adenocarcinoma causing ruptured cholecystitis and cholangitis,with metastases to retroperitoneal lymph nodes.Minimally invasive techniques,including endoscopic duct brushings and percutaneous lymph node biopsy,were inadequate for tissue diagnosis.Therefore,this case required exploratory laparo-tomy,open cholecystectomy,and periaortic lymph node dissection for histopathological assessment and definitive diagnosis.Hodgkin lymphoma was present in the lymph nodes while the gallbladder specimen had no evidence of malignancy.CONCLUSION This clinical scenario highlights the importance of histopathological assessment in diagnosing gallbladder malignancy in a patient with gallbladder perforation and a grossly positive positron emission tomography/computed tomography scan.For both gallbladder adenocarcinoma and Hodgkin lymphoma,medical and surgical therapies must be tailored to the specific disease entity in order to achieve optimal long-term survival rates.
文摘BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.
文摘Epstein Barr virus （EBV） positive mucocutaneous ulcers（EBVMCU） form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract （GIT）. Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. Wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn＇s disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn＇s disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.
基金supported by the National Natural Science Foundation of China(No.30900597)
文摘This study aims to examine the levels of circulating endothelial progenitor cells (cEPCs) in the peripheral blood of patients with non-Hodgkin lymphoma (NHL) and their correlation with the tumor stage. Forty-one patients with biopsy-proven NHL and 16 healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation, and cEPCs were characterized by triple staining using antibodies against CD133, CD34 and vascular endothelial growth factor receptor-2 (VEGFR-2, CD309) and quantified by flow cytometry. In NHL patients, the number of cEPCs was significantly greater than in control group (P=0.000). The cEPCs counts in patients with NHL of stage Ⅲ-Ⅳ were significantly greater than in stage Ⅰ-Ⅱ (P=0.010). FACS analysis revealed that the number of cEPCs in NHL patients had no correlation with the gender (P=0.401) or the pathological category (P=0.852). It was suggested that the over-expression of cEPCs in NHL patients may serve as a novel biomarker for disease progression in NHL.
基金sponsored by Scientific Research Foundation for the Returned Overseas Chinese ScholarsMinistry of Human Resources and Social SecurityBeijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(No.XMLX201502)
文摘Objective: High-dose chemotherapy(HDC) followed by autologous stem cell transplantation(ASCT) is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma(NHL).However,a proportion of patients do not respond to ASCT.^(18)F-fluorodeoxyglucose(FDG) positron emission tomography(PET)/computed tomography(CT) has been widely used for staging,response evaluation,and prognosis prediction.Here,we investigated the prognostic role of PET/CT in NHL patients before and after ASCT.Methods: A retrospective study was conducted at Peking University Cancer Hospital.All NHL patients who underwent ASCT between March 2010 and July 2016 were identified.Patients who had PET/CT scan before and after ASCT were included.Deauville criteria(5-point scale) were used to interpret PET scans.Univariate and multivariate survival analyses were performed using Cox regression.The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic(ROC) curve.Results: In total,79 patients were enrolled in this study.In univariate analysis,pre-and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival(PFS) and overall survival(OS).Patients with negative pre-ASCT PET result demonstrated significantly better PFS(84.2% vs.54.2%) and OS(89.2% vs.63.6%) than patients with positive pre-ASCT PET result.PFS(91.6% vs.25.3%) and OS(96.5% vs.36.8%) were also significantly different between patients with negative and positive post-ASCT PET result.Multivariate analysis also showed a significant association between survival and post-ASCT PET result.ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone.Combined pre-and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation.Deauville criteria score >3 was identified as the best cutoff value for post-ASCT PET.Conclusions: Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT.The prognostic significance can be improved when combining preASCT PET result with post-ASCT PET result.Deauville criteria can be used for interpreting PET scans in this scenario.
文摘Although Epstein-Barr virus(EBV)is present in the malignant Hodgkin/Reed-Sternberg(HRS)cells of a proportion of cases of classical Hodgkin lymphoma(c HL),how the virus contributes to the pathogenesis of this disease remains poorly defined.It is clear from the studies of other EBV-associated cancers that the virus is usually not sufficient for tumor development and that other oncogenic co-factors are required.This article reviews what is known about the contribution of EBV to the pathogenesis of c HL and focuses on emerging evidence implicating chronic inflammation as a potential oncogenic co-factor in this malignancy.
基金supported by the Natural Science Foundation of Heilongjiang Province(Grant No.JJ2018ZR167)Health and Family Planning Commission of Heilongjiang Province(Grant No.2016-097&2016-102)the Fundamental Research Funds for the Provincial Universities(Grant No.2017LCZX95)
文摘Objective: Although the prognostic value of programmed cell death-ligand 1(PD-L1) expression in non-Hodgkin lymphoma(NHL) has been evaluated in many studies, the results remain controversial. To investigate the prognostic role of PD-L1 expression and the association between PD-L1 expression and clinicopathological features of NHL, we performed a meta-analysis.Methods: The Pub Med, EMBASE, and Cochrane Library databases were searched up to November 30, 2017. The hazard ratio(HR), 95% confidence interval(CI), and odds ratios(OR) with 95% CIs were combined to evaluate the association of PD-L1 expression with overall survival(OS) and clinicopathological features. Review manager 5.3 and STATA 12.0 were used in this meta-analysis.Results: A total of 2,005 patients across nine studies were enrolled in our meta-analysis, and the pooled results showed that high PD-L1 expression was associated with a poor prognosis(HR=2.04, 95% CI: 1.18–3.54, P=0.01). In the subgroup analysis according to histology types, pooled results demonstrated that an increased PD-L1 expression was an unfavorable prognostic factor for diffuse large B-cell lymphoma(HR=1.92, 95% CI: 1.06–3.48, P=0.03) but not for natural killer/T-cell lymphoma(HR=2.41, 95%CI: 0.47–12.22, P=0.29). Pooled ORs indicated that PD-L1 expression was higher in NHL with international prognostic indices of≥3. However, PD-L1 expression had no correlation with gender, age, disease stage, lactate dehydrogenase level, B symptoms, and germinal center B-cell-like lymphoma.Conclusions: High PD-L1 expression was a poor prognostic biomarker in patients with NHL. Because of our limited sample size,high-quality studies with larger sample sizes are needed to validate our results.
文摘At present,approximately 20%of Hodgkin lymphomas(HL)are relapsed and refractory,and therapeutic methods including chemotherapy,radiotherapy,and even stem cell transplantation are unsatisfactory.Brentuximab vedotin,composed of CD30 antibody and a chemotherapeutic agent,is a new targeted drug that eradicates tumor cells by binding to the CD30 antigen on their surface.In clinical trials,the response rate and complete remission rate of this drug were 73%and 40%,respectively,for relapsed and refractory HL.Here we report a case of CD30-positive relapsed and refractory HL that was treated with brentuximab.Before the treatment with brentuximab,the patient underwent chemotherapy,radiotherapy,and autologous stem cell transplantation.However,the disease continued to progress,affecting multiple organs and prompting symptoms such as persistent fever.After the treatment with brentuximab,the patient′s condition improved.Body temperature returned to normal after 4 days.Lung nodules were reduced in size and number after a single course of treatment,and PET/CT showed partial remission and complete remission after 3 and 6 courses of treatment,respectively.The entire treatment process progressed smoothly,though the patient experienced some symptoms due to chemotherapy,including peripheral neuritis of the limbs,irritating dry cough,and mild increase in aminotransferase.No serious adverse effects were observed.The current general condition of the patient is good;the continuous complete remission has amounted to 6 months.
文摘In order to investigate the expression change of survivin in non-Hodgkin lymphoma (NHL) and its possible effects on NHL development, the expression of survivin, Ki-67, caspase3 and FVIIIRAg in reactive lymphoid hyperplasia (RH) and NHL was detected by immunohistochemical assay, and apoptosis index (AI) in RH and NHL by TUNEL analysis. The results showed that the expression of survivin is significantly higher in aggressive NHL than in indolent NHL (P<0.01), while there was no statistically significant difference between RH and indolent NHL (P>0.05). The expression of survivin had a significantly positive correlation with the expression of Ki-67 and FVIIIRAg (r=0.6495, 0.6635, respectively, both P<0.01), and a negative correlation with the expression of cas-pase3 and AI (r=-0.5820, -0.6013, respectively, P<0.01). It was suggested that survivin may contribute to the progression of NHL by playing an important role in promoting cell proliferation, inhibiting cell apoptosis and enlisting angiogenesis. Survivin expression is closely related to malignant grade and therefore may be considered an important prognostic factor of NHL.
文摘The relationship between angiogenesis and eukaryotic translation initiation factor 4E (EIF4E) expression level in non-Hodgkin lymphoma (NHL) was studied. Mean microvessel density (MVD) and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3.1 (+) and transfected into Raji cells. A series of angiogenesis related factors,including vascular endothelial growth factor (VEGF), matrix metalloproteinases 9 (MMP-9) and tissue inhibitor of metalloproteinases-2 (TIMP-2) proteins were detected by Western blot. The results showed that: (1) The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas(P<0.05)and the expression of EIF4E was positively correlated with MVD in lymph node of NHL(r=0.695, P<0.01). (2) Antisense EIF4E eukaryocytic expression vector (pcDNA3.1-EIF4Eas) was constructed successfully. (3) EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells (NHPMC), and blockage of EIF4E expression brought down the expression of VEGF and MMP-9. However, TIMP-2 was undetectable in Raji cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL.
文摘Primary gastric lymphomas(PGLs)are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and molecularly.Their main histological types are diffuse large B-cell lymphoma(DLBCL)or mucosaassociated lymphoma tissue.PGL has been one of the main fields of clinical research of our group in recent years.Although gastric DLBCLs are frequent,sufficient data to guide optimal care are scarce.Until today,a multidisciplinary approach has been applied,including chemotherapy,surgery,radiotherapy or a combination of these treatments.In this minireview article,we provide an overview of the clinical manifestations,diagnosis and staging of these diseases,along with their molecular pathogenesis and the most important related clinical published series.We then discuss the scientific gaps,perils and pitfalls that exist regarding the aforementioned studies,in parallel with the unmet need for future research and comment on the proper methodology for such retrospective studies.Aiming to fill this gap,we retrospectively evaluated the trends in clinical presentation,management and outcome among 165 patients with DLBCL PGL who were seen in our institutions in 1980-2014.The study cohort was divided into two subgroups,comparing the main 2 therapeutic options[cyclophosphamide doxorubicin vincristine prednisone(CHOP)vs rituximab-CHOP(R-CHOP)].A better outcome with immunochemotherapy(R-CHOP)was observed.In the next 2 mo,we will present the update of our study with the same basic conclusion.
文摘Background: Non-Hodgkin’s lymphoma is an aggressive malignant disease in children and adolescents. Although it is the fourth most common malignancy in Saudi children as reported in Saudi cancer registry, less information is available about pediatric Non-Hodgkin lymphoma and its outcome in Saudi Arabia. Study Objectives: To provide demographic data, disease characteristics, treatment protocol, toxicity and outcome of treatment in children & adolescents with Non-Hodgkin’s lymphoma treated at KFMC. This study will form base line for future studies about pediatric Non-Hodgkin’s lymphoma in KFMC, which may help to improve outcome for children with cancer in Saudi Arabia. Study Patients and Method: We retrospectively analyzed 28 children and adolescents diagnosed to have Non-Hodgkin’s lymphoma at KFMC between December 2006 and December 2013, followed-up through June 2014. Results: Of the 28 patients, 10 (35.7%) girls and 18 (64.3%) boys, the male-to-female ratio was 1.8;1. The median age at time of diagnosis was 6.4 years old (range 2.0 to 13.0 years old). The majority of patients (64.3%) were aged between 5 and 12 years old. Burkitt’s lymphoma BL/BLL was the most common pathological subtype (60.7%), and DLBCL was the second most common subtype (21.4%). Abdominal and Retroperitoneal involvement was the most common primary site (78.6%) including the ileocaecal region. Most of the children presented with advanced Stage III and IV (75%), Cytogenetic study which screens specifically for the t (8;14) (q24;q32) a characteristic genetic feature of Burkitt’s Lymphoma was obtained from 21 patients, variant rearrangement was observed in 3/21 samples and complex chromosomes karyotype in addition to IGH/MYC rearrangement was observed in 2/21 samples. Those patients presented with very aggressive lymphoma and combined BM and CNS involvement. We use the French-American-British Mature B-Cell Lymphoma 96 Protocol (FAB LMB 96) for treatment fornewly diagnosed Mature B-Cell type NHL and high risk ALL CCG 1961 Protocol for lymphoblastic lymphoma and international Anaplastic Large Cell Lymphoma 99 Study Protocol for ALCL. The median follow-up in patients not experiencing an adverse event was 53.1 months. The estimated 3-year EFE and OS rates in the entire cohort of patients with newly diagnosed NHL treated in the KFMC were 85.2% and 89.2% respectively;Overall survival (OS) rate of patients with mature B-cell-NHL was 88.9%. Conclusion: The outcomes and survival in our small series appeared to be excellent compared with those reported in other international trials even though most of our patients presented in advanced stage of the disease. We feel that the importance of the current study is to document the relative distribution of various types of pediatric non-Hodgkin’s lymphomas and age-specific distribution in different Histological subtypes.
基金supported by the National Key Research and Development Program of China(No.2020YFA0803201)the National Natural Science Foundation of China(No.31830053,31920103007,22207084)the Fundamental ResearchFunds fortheCornellUniversity(No.22120220463).
文摘The interaction between cluster of differentiation 47(CD47)and signal regulatory proteinα(SiRPa)protects healthy cells from macrophage attack,which is crucial for maintain-ing immune homeostasis.Overexpression of CD47 occurs widely across various tumor cell types and transmits the"don't eat me"signal to macrophages to avoid phagocytosis through binding to SIRPa.Blockade of the CD47-SIRPa axis is therefore a promising approach for cancer treat-ment.Lymphoma is the most common hematological malignancy and is an area of unmet clin-ical need.This review mainly described the current strategies targeting the CD47-SIRPa axis,including antibodies,SiRPaFc fusion proteins,small molecule inhibitors,and peptides both in preclinical studies and clinical trials with Hodgkin lymphoma and non-Hodgkin lymphoma.
