Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma

BACKGROUND Chemotherapy for malignant tumors can cause brain changes and cognitive impairment,leading to chemotherapy-induced cognitive impairment(CICI).Current research on CICI has focused on breast cancer and Hodgkin’s lymphoma.Whether patients with non-Hodgkin’s lymphoma(NHL)undergoing chemo-therapy have cognitive impairment has not been fully investigated.therapy have cognitive impairment has not been fully investigated.AIM To investigate whether NHL patients undergoing chemotherapy had cognitive impairments.METHODS The study included 100 NHL patients who were required to complete a compre-hensive psychological scale including the Brief Psychiatric Examination Scale(MMSE)at two time points:before chemotherapy and within 2 wk of two chemo-therapy courses.A language proficiency test(VFT),Symbol Number Pattern Test(SDMT),Clock Drawing Test(CDT),Abbreviated Daily Cognition Scale(ECog-12),Prospective and Retrospective Memory Questionnaire,and Karnofsky Perfor-mance Status were used to assess cognitive changes before and after chemo-therapy.RESULTS The VFT scores for before treatment(BT)and after treatment(AT)groups were 45.20±15.62,and 42.30±17.53,respectively(t-2.16,P<0.05).The CDT scores were 8(3.5-9.25)for BT and 7(2.5-9)for AT groups(Z-2.1,P<0.05).Retrospective memory scores were 13.5(9-17)for BT and 15(13-18)for AT(Z-3.7,P<0.01).The prospective memory scores were 12.63±3.61 for BT and 14.43±4.32 for AT groups(t-4.97,P<0.01).The ECog-12 scores were 1.71(1.25-2.08)for BT and 1.79(1.42-2.08)for AT groups(Z-2.84,P<0.01).The SDMT and MMSE values did not show a significant difference between BT and AT groups.CONCLUSION Compared to the AT group,the BT group showed impaired language,memory,and subjective cognition,but objec-tive cognition and execution were not significantly affected.

HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients' outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients' quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.

SENEX-mediated CDK4/6 inhibition promotes senescence and confers apoptosis resistance in B-cell non-Hodgkin lymphoma

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.

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

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

Primary Non-Hodgkin’s Malignant Lymphoma of the Uterus at the Reference Hospital of Maradi/Niger: A Case Report

Malignant non-Hodgkins lymphoma (MHNL) of the uterus is uncommon. We report a case diagnosed on the basis of histologic and immunohistochemical studies of a hysterectomy specimen induced by a very painful pelvic mass in a 50-year-old patient with no previous history of the disease. It was classified as Ann Arbor IV Bb after imaging, given the medullary infiltration and signs of clinical and biological evolutivity: the patient had received two courses of chemotherapy, CHOP protocol. She died 23 days after the second treatment due to a hypertensive crisis.

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

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

Research advances in reactivation of hepatitis virus after chemotherapy for non-Hodgkin’s lymphoma-combined hepatitis B virus infection

Infection rate of hepatitis B virus (HBV) in our country remains high. Many patients showed combined HBV infection; the most common blood system disease is non-Hodgkin’s lymphoma (NHL)-combined HBV infection. Drugs used in treating lymphoma may induce different degrees of HBV reactivation. Such condition may lead to hepatic failure or death. Currently, scholars pay increasing attention to reactivation of HBV by rituximab and/or chemotherapy for NHL-combined HBV patients. This study summarizes research advances in this topic, with a view of providing background information for further research.

Primary early-stage intestinal and colonic non-Hodgkin's lymphoma: Clinical features, management, and outcome of 37 patients

AIM： To analyze the clinical features, management, and outcome of treatment of patients with primary intestinal and colonic non-Hodgkin＇s lymphoma （PICL）. METHODS： A retrospective study was performed in 37 patients with early-stage PICL who were treated in our hospital from 1958 to 1998. Their clinical features, management, and outcome were assessed. Prognostic factors for survival were analyzed by univariate analysis using the Kaplan-Meier product-limit method and log-rank test. RESULTS： Twenty-five patients presented with Ann Arbor stage Ⅰ PICL and 12 with Ann Arbor stage Ⅱ PICL. Thirty-five patients underwent surgery （including 31 with complete resection）, 22 received postoperative chemotherapy or radiotherapy or both. Two patients with rectal tumors underwent biopsy and chemotherapy with or without radiotherapy. The 5- and 10-year overall survival （OS） rates were 51.9% and 44.5%. The corresponding diseasefree survival （DIS） rates were 42.4% and 37.7%. In univariate analysis, multiple-modality treatment was associated with a better DFS rate compared to single treatment （P= 0.001）. While age, tumor size, tumor site, stage, histology, or extent of surgery were not associated with OS and DFS, use of adjuvant chemotherapy significantly improved DFS （P = 0.031） for the 31 patients who underwent complete resection. Additional radiotherapy combined with chemotherapy led to a longer survival than chemotherapy alone in six patients with gross residual disease after surgery or biopsy.CONCLUSION： Combined surgery and chemotherapy is recommended for treatment of patients with PICL, Additional radiotherapy is needed to improve the outcome of patients who have gross residual disease after surgery.

Primary intestinal non-Hodgkin's lymphoma:A clinicopathologic analysis of 81 patients

AIM:To analyze the clinicopathologic features and the prognosis of primary intestinal lymphoma.METHODS:Patients were included in the study based on standard diagnostic criteria for primary gastrointesti-nal lymphoma,and were treated at Sun Yat-sen Univer-sity Cancer Centre between 1993 and 2008.RESULTS:The study comprised 81 adults.The most common site was the ileocaecal region.Twenty-two point two percent patients had low-grade B-cell lym-phoma.Fifty-one point nine percent patients had high-grade B-cell lymphoma and 25.9% patients had T-cell lymphoma.Most patients had localized disease.There were more patients and more early stage diseases in the latter period,and the origin sites changed.The ma-jority of patients received the combined treatment,andabout 20% patients only received nonsurgical therapy.The wverall survival and event-free survival rates after 5 years were 71.6% and 60.9% respectively.The mul-tivariate analysis revealed that small intestine and ileo-caecal region localization,B-cell phenotype,and normal lactate dehydrogenase were independent prognostic factors for better patient survival.Surgery based treat-ment did not improve the survival rate.CONCLUSION:Refined stratification of the patients according to the prognostic variables may allow indi-vidualized treatment.Conservative treatment may be an optimal therapeutic modality for selected patients.

Prognostic value of pre-and post-transplantation 18F-fluorodeoxyglucose positron emission tomography results in non-Hodgkin lymphoma patients receiving autologous stem cell transplantation

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. lSF-fluorodeoxyglueose （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 cutoffvalue 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 pre- ASCT PET result with post-ASCT PET result. Deauville criteria can be used for interpreting PET scans in this scenario.

A case of primary isolated non-Hodgkin’s lymphoma of the esophagus in an immunocompetent patient

Primary non-Hodgkin’s lymphoma of the esophagus is a rare disease.A case of primary isolated nonHodgkin’s lymphoma of the esophagus in a 77-yearold man without acquired immunodeficiency syndrome is presented.We describe the clinical features and the imaging findings(barium swallow,endoscopic ultrasonography and CT)of a biopsy proven B-cell lymphoma with diffuse transmural involvement of the esophagus wall,which was discovered incidentally.We also briefly review the literature.

Primary gastric non-Hodgkin lymphomas:Recent advances regarding disease pathogenesis and treatment

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.

Positron emission tomography/computerized tomography in the evaluation of primary non-Hodgkin's lymphoma of prostate

Primary malignant lymphoma of the prostate is exceedingly rare.Here we report a case of a 65-year-old man who presented with increased urinary frequency,urinary urgency,and urinary incontinence for two years.Benign prostatic hypertrophy was suspected at primary impression.Ultrasound revealed a hypoechoic lesion of the prostate.The total serum prostate-specific antigen was within normal range.Positron emission tomography/computerized tomography(PET/CT)showed a hypermetabolic prostatic lesion.Prostate biopsy was consistent with a non-germinal center diffuse large B cell lymphoma.There was complete remission of the prostatic lesion following six cycles of chemotherapy as shown on the second PET/CT imaging.18F-fluoro-deoxy glucose PET/CT is not only a complement to conventional imaging,but also plays a significant role in the diagnosis and evaluation of treatment response of prostatic lymphoma.

Dysentery caused by Balantidium coliin a patient with non-Hodgkin's lymphoma from Turkey

Balantidium coli is the only parasitic ciliate of man. It is a flattened oval organism covered with cilia, and a gullet at the anterior end. It is infrequently pathogenic for man,although epidemic buds in tropical zones have been described. The infection fundamentally affects the colon and causes variable clinic pictures, from asymptomatic to serious dysenteric forms. We present a case of parasitologically diagnosed as causes of diarrhea in a patient with non Hodgkin's lymphoma from Turkey.In order to find out the causative etiologic agent of diarrhea,stool samples were examined by native,lugol and flotation methods and we detected moving trophozoites, which were approximately 60μm long and 35μm wide.These bodies were diagnosed as Balantidium coli This case underlines that Balantidium coli should also be considered as a possible pathogen in immunocompromised patients with diarrhea.

Molecular markers(PECAM-1,ICAM-3,HLA-DR)determine prognosis in primary non-Hodgkin's gastric lymphoma patients

AIM： To investigate the prognostic significance of PECAM-1, ICAM-3 and HLA-DR antigens in patients with primary non-Hodgkin＇s gastric lymphoma. METHODS： We immunohistochemically studied PECAM-1, ICAM-3 and HLA-DR antigen expression in 36 B-cell MALT-type primary gastric lymphoma patients. Ten non-malignant and ten healthy gastric tissue specimens were used as controls. Clinicopathological and survival data were correlated with the staining results. RESULTS： HLA-DR antigen expression was detected in 33 gastric lymphoma patients （91.7%） and 6 nonmalignant patients （54.5%）. PECAM-1 stained tumor cells of 10 patients （27.8%）, endothelial cells of 9 patients （25%） and inflammatory infiltrate of 4 patients （40%） with benign gastric disease. ICAM-3 expression was observed on the tumor cells of 17 patients （47.2%）, while 5 non-malignant patients （50%） were stained positive as well. None of the healthy controls was stained for any of the genes studied. In the multivariate analysis, HLA-DR antigen and PECAM-1 were proved to be statistically significant independent prognostic factors associated with a favourable and an unfavourable prognosis respectively （P= 0.009 and P= 0.003）. In the univariate analysis, PECAM-1（＋）/ICAM-3（-） and HLA-DR（-）/ICAM-3（-） patients exhibited a significantly decreased overall survival compared to those with the exactly opposite gene expression patterns （P=0.0041 and P= 0.0091, respectively）. Those patients who were HLA-DR（＋ ）/ICAM-3（＋ ）/PECAM-I（-） （n = 8） had a significantly higher survival rate compared to the rest of the group （n = 24） （P= 0.0289）. CONCLUSION： PECAM-1, ICAM-3 and HLA-DR are representative markers of tumor expansion potential and host immune surveillance respectively. Their combined use may help us to identify high-risk patients who could benefit from more aggressive therapeutic protocols.

Correlation between Increased Circulating Endothelial Progenitor Cells and Stage of non-Hodgkin Lymphoma

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. Pe- ripheral 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-1V 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.

Complete regression of myocardial involvement associated with lymphoma following chemotherapy

Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence.We describe the case of a 26 year old man who had initially been diagnosed with myocardial infiltration on an echocardiogram,presenting with a testicular mass and unilateral peripheral facial paralysis.On admission,electrocardiograms(ECG)revealed negative T-waves in all leads and ST-segment elevation in the inferior leads.On twodimensional echocardiography,there was infiltration of the pericardium with mild effusion,infiltrative thickening of the aortic walls,both atria and the interatrial septum and a mildly depressed systolic function of both ventricles.An axillary biopsy was performed and reported as a T-cell lymphoblastic lymphoma(T-LBL).Following the diagnosis and staging,chemotherapy was started.Twenty-two days after finishing the first cycle of chemotherapy,the ECG showed regression of T-wave changes in all leads and normalization of the ST-segment elevation in the inferior leads.A followup two-dimensional echo confirmed regression of the myocardial infiltration.This case report illustrates a lymphoma presenting with testicular mass,unilateral peripheral facial paralysis and myocardial involvement,and demonstrates that regression of infiltration can be achieved by intensive chemotherapy treatment.To our knowledge,there are no reported cases of T-LBL presenting as a testicular mass and unilateral peripheral facial paralysis,with complete regression of myocardial involvement.

Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-Hodgkin's lymphoma infi ltration

To investigate the simultaneous occurrence of hepatocellular carcinoma and non-Hodgkin's lymphoma, we report the case of a 70 year old patient with a primary diagnosis of non-Hodgkin's lymphoma in 2002. In a routine follow up investigation of his chronic lymphocytic leukemia a newly detected mass in the Couinaud's segments 2 and 3 was found. No hepatitis C virus or hepatitis B virus infection or cirrhosis was evident. After laparoscopic segmentectomy the histological examination revealed a hepatocellular carcinoma. While the relation between liver parenchyma damages and hepatocellular carcinoma or non-Hodgkin's lymphoma is well known, only a few publications have focused on the coexistence of hepatocellular carcinoma and non-Hodgkin's lymphoma. With this case we demonstrate the coexistence of these diseases without having a pre- damaged liver parenchyma.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

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.

Hepatitis viruses and non-Hodgkin's lymphoma: A review

Non-Hodgkin's lymphoma(NHL) is among the haematological malignancies with high prevalence worldwide, causing estimated 355 900 new cases and 191 400 deaths in 2008. High prevalence of NHL is documented in economically more developed areas while low prevalence is observed in less developed areas of the globe. A wide array of environmental factors have been reported to be either directly involved or in modifying the risk of NHL development. In addition to these factors, a number of infectious agents, chiefly viruses have also been implicated in the development of NHL. This article reviews the available literature to discuss the role of hepatitis viruses in NHL development, possible mechanisms of lymphomagenesis and also identify the areas in which further research is required to better understand this disease. A brief discussion on the clinical aspects such as classification, staging, treatment approaches have also been included in this article.