Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a non-Hodgkin lymphoma that originates in the central nervous system(CNS)and is exclusively limited to the CNS.Although most PCNSLs are diffuse large B-cell lymphomas,primary CNS T-cell lymphomas(PCNSTLs)are rare.PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging(MRI).To the best of our knowledge,non-enhancing PCNSTL has not been reported previously.CASE SUMMARY A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks.Initial MRI showed asymmetric T2-hyperintense lesions within the brain.No enhancement was observed on the contrast-enhanced T1 image.The initial diagnosis was neuro-Behçet’s disease.Despite high-dose steroid therapy,no alterations in the lesions were identified on initial MRI.The patient’s symptoms deteriorated further.An MRI performed one month after the initial scan revealed an increased lesion extent.Subsequently,brain biopsy confirmed the diagnosis of PCNSTL.The patient underwent definitive combined chemoradiotherapy.However,the patient developed bacteremia and died of septic shock approximately three months after diagnosis.CONCLUSION The absence of enhancement in the lesion did not rule out PCNSTL.A biopsy approach is advisable for pathological confirmation.

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.

Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin＇s lymphoma

Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.

Heterochronous multiple primary prostate cancer and lymphoma:A case report

BACKGROUND Multiple primary malignant tumors(MPMTs)are rare type of cancer,especially when solid tumors are the first and lymphoma is the second primary malignancy.We report a patient with heterochronous MPMTs consisting of prostate cancer and rectal diffuse large B-cell lymphoma(DLBCL).CASE SUMMARY We report a 77-year-old male patient diagnosed with prostate cancer who was treated with radiation therapy and one year of endocrine therapy with bicalutamide(50 mg per day)and an extended-release implant of goserelin(1/28 d).Seven years later,rectal DLBCL with lung metastases was found.CONCLUSION Although rare,the possibility of prostate cancer combined with a double primary cancer of DLBCL can provide a deeper understanding.

Massive bleeding in small intestinal mucosa-associated lymphoid tissue lymphoma associated with COVID-19 infection:a case report

The increased risk of mucosa-associated lymphoid tissue(MALT)lymphoma is closely associated with chronic antigenic stimulation,with infection being the most common cause of recurrence.Lesions are usually associated with the gastrointestinal tract,and the involvement of small intestinal is rare.Recent studies have established a close relationship between novel coronavirus 2019(COVID-19)and the occurrence and progression of various diseases.This article presents a rare case of a small intestinal MALT lymphoma.The patient was initially admitted with COVID-19 pneumonia and subsequently developed gastrointestinal bleeding during hospitalization.Medical and endoscopic treatments were ineffective,and an emergency exploratory laparotomy was performed.The affected segment of the small intestine was excised,and a pathological biopsy confirmed the diagnosis of MALT lymphoma.This case underscores the significance of raising clinical awareness of this condition among health care professionals.

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.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

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.

Pediatric-type follicular lymphoma in a Crohn’s disease patient receiving anti-α4β7-integrin therapy:A case report

BACKGROUND Patients with autoimmune conditions receiving immunosuppressants are at risk of non-Hodgkin lymphomas(NHL).Vedolizumab(anti-α4β7-integrin antibody),a treatment-of-choice for Crohn’s disease(CD),reduces inflammatory lymphocyte trafficking into the intestinal mucosa.This effect is believed to be confined to the colon.CASE SUMMARY We report the case of a CD patient on vedolizumab for five years who developed pediatric-type follicular lymphoma.Work-up prior to therapy revealed a reduction in circulating T-lymphocytes and their suppressed response to mitogens.Rituximab,cyclophosphamide,vincristine,and prednisone chemoimmunotherapy resulted in durable lymphoma remission,and vedolizumab treatment was continued.While the patient’s T-lymphocyte population and immunoglobulin production recovered,the T-lymphocyte mitogen response remained suppressed.CONCLUSION This patient’s NHL may be linked to receiving anti-α4β7 therapy.Further research could be beneficial to determine if proactive surveillance for NHL and other systemic diseases is indicated in patients on vedolizumab.

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.

Non Hodgkin’s Lymphoma with Right Atrial Intra Cardiac Metastases

Background: Diffuse Large B-Cell Lymphoma (DLBCL) is the most variant of Non-Hodgkin’s Lymphoma (NHL) and also the most common variant with secondary intracardiac masses. Case summary: 7 years old child presented to emergency with acute decompensated cardiac failure, ascites and tender hepatomegaly. 2D echo evaluation was suggestive of large intracardiac mass in the right atrium almost completely obstructing Tricuspid valve orifice, gross pericardial effusion and dilated Inferior Vena Cava (IVC). Emergency tumor excision surgery was performed which revealed 4 × 4 cm pinkish firm mass arising from anterior Tricuspid annulus which was completely excised. Child was extubated on postoperative day (POD) 0 and was on minimal inotropic support. Ascites reduced significantly on POD1 allowing abdominal palpation which revealed a mass in the epigastric region. This prompted evaluation by pediatrician and oncology workup suggestive of increased 18-Flouro Deoxy Glucose (18-FDG) uptake in the mediastinum, abdomen, bilateral proximal thighs, all mediastinal lymph nodal stations, bilateral lung hilar stations 10R, 10L involving all encasing the heart and great vessels with pleural deposits, Celiac trunk, superior Mesenteric Artery (SMA), Portal vein, IVC and abdominal aorta. Histo pathology Examination (HPE) and Immuno Histo Chemistry (IHC) of intracardiac mass revealed DLBCL which is metastatic in nature. Chemotherapy was started as per (French American British Lymphomes Malins B) FAB LMB-96 protocol with the child currently in the Induction phase having poor prognosis and less survival interval. Conclusion: Surgery can be considered a treatment option for metastatic intracardiac masses during emergency scenarios like cardiogenic shock to relieve obstruction along the pathway of blood flow in the heart even though we may not be able to completely excise the tumor surgically.

Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement

AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.

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.

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.

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.

Correlation between the Human Development Index and the Incidence and Mortality of Non-Hodgkin Lymphoma

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.

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.

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 multi-center,open-label,randomized,parallel-controlled phase II study comparing pharmacokinetic,pharmacodynamics and safety of ripertamab(SCT400)to rituximab(Mab Thera?)in patients with CD20-positive B-cell non-Hodgkin lymphoma

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.

Expression of survivin in Human Non-Hodgkin Lymphoma and Its Correlation with Proliferation and Angiogenesis

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 expres- sion of survivin had a significantly positive correlation with the expression of Ki-67 and FVSRAg （r=0.6495, 0.6635, respectively, both P〈0.01）, and a negative correlation with the expression of caspase3 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.