Efficacy of anti-CD 20 monoclonal antibody in combination with Gemcitabine-based chemotherapy regimen in children with recurrent diffuse large B-cell lymphoma / 中华实用儿科临床杂志

Objective:To investigate the efficacy of anti-CD 20 monoclonal antibody in combination with Gemcitabine-based chemotherapy regimen in children with recurrent diffuse large B-cell lymphoma (DLBCL). Methods:The clinical data of 62 children with DLBCL admitted to the Department of Pediatrics, Yantai Mountain Hospital of Yantai City and the Department of Pediatrics, Muping District Traditional Chinese Medicine Hospital in Yantai City from January 2010 to January 2018 were analyzed retrospectively.Different treatment options were selected according to the children′s stage and the presence of risk factors such as huge tumors.Among them, 32 cases in the control group were treated with the Gemcitabine-based treatment plan (Gemcitabine+ Cisplatin+ Dexamethasone treatment). Thirty patients in the study group were treated with anti-CD 20 monoclonal antibody on the basis of the control group for a total of 4 cycles (21 d per cycle). After 4 cycles of treatment, the clinical efficacy, the positive expression of forkhead box protein P1 (FOXP1) and B-cell lymphoma factor-6 (Bcl-6) before and after treatment, the occurrence of adverse reactions and survival[3-year progression-free survival (PFS), 3-year overall survival (OS)] were evaluated.The measurement data that meets the normal distribution is expressed that the t test is used, and the counting data is represented by (%), and the χ2 test is used.Level data is compared with ranking and inspection. Results:All patients were followed up to March 2021.The total response rate (RR) and disease control rate (DCR) of the study group were 93.33% (28/30 cases) and 96.67% (29/30 cases), respectively.The RR and DCR of the control group were 68.75% (22/32 cases) and 81.25% (26/32 cases), respectively.The RR of the study group was higher than that of the control group ( χ2=5.995, P<0.05), and there was no statistical difference in DCR between the two groups ( χ2=3.674, P>0.05). After treatment, the positive expression rate of FOXP1 in the study group and the control group was lower than before treatment[23.33% (7/30 cases) vs. 76.67% (23/30 cases); 50.00% (16/32 cases) vs. 75.00% (24/32 cases), χ2=17.067, 4.267, all P<0.05], and the positive expression rate of the study group was lower than that of the control group ( χ2=4.179, P<0.05). After treatment, the positive expression rate of Bcl-6 in the study group and the control group was higher than before treatment[86.67% (26/30 cases) vs. 26.67% (8/30 cases); 62.50% (20/32 cases) vs. 31.25% (10/32 cases), χ2=21.991, 6.275, all P<0.05], and the positive expression rate of the study group was higher than that of the control group ( χ2=4.723, P<0.05). There was no significant difference between the study group and the control group in the level of gastrointestinal reactions, elevated transa-minase, and decreased white blood cell ( Z=-1.074, -1.078, -0.834, all P>0.05). There was a difference between the 3-year PFS survival curve and the 3-year OS survival curve between the two groups ( χ2=3.997, 4.723, all P<0.05). Conclusions:Anti-CD 20 monoclonal antibody combined with Gemcitabine-based chemotherapy is effective for children with DLBCL, and will not significantly increase the adverse reactions in children.

Progress of chimeric antigen receptor T-cell for treatment of follicular lymphoma / 肿瘤研究与临床

Follicular lymphoma (FL) is usually occult, with a wide range of disease manifestations and prognosis. In recent years, with the combination of anti-CD20 monoclonal antibody and standard chemotherapy methods, as well as the use of immunomodulators and hematopoietic stem cell transplantation, the survival rate of FL patients has been greatly improved, but it is still considered to be an incurable disease. Recent studies have shown that the chimeric antigen receptor T-cell (CAR-T) therapy can improve the survival rate and the prognosis of FL patients. The article will elaborate on the mechanism, clinical research progress, adverse reactions and limitations of CAR-T in the treatment of FL.

Progress of chimeric antigen receptor T-cell for treatment of follicular lymphoma / 肿瘤研究与临床

Follicular lymphoma (FL) is usually occult, with a wide range of disease manifestations and prognosis. In recent years, with the combination of anti-CD20 monoclonal antibody and standard chemotherapy methods, as well as the use of immunomodulators and hematopoietic stem cell transplantation, the survival rate of FL patients has been greatly improved, but it is still considered to be an incurable disease. Recent studies have shown that the chimeric antigen receptor T-cell (CAR-T) therapy can improve the survival rate and the prognosis of FL patients. The article will elaborate on the mechanism, clinical research progress, adverse reactions and limitations of CAR-T in the treatment of FL.

Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma / 中华血液学杂志

Objective: To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20(+) B-cell non-Hodgkin's lymphoma (NHL). Methods: Nine patients with CD20(+) B-cell NHL received dose-escalating IBI301 infusions (250 mg/m(2), n=3; 375 mg/m(2), n=3; 500 mg/m(2), n=3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m(2), 375 mg/m(2), 500 mg/m(2) dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events (AE). The ratios of CD19(+), CD20(+) B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics. Results: Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m(2) group, 14 events of AE in 375 mg/m(2) group and 20 events of AE in 500 mg/m(2) group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE (SAE) were reported. No dose-limiting toxicity (DLT) events were observed in the study. The ratio of CD20(+) and CD19(+) B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM. Conclusions: The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients. Clinical trial registration: Chinadrugtrials, CTR20140762.

Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin’s lymphoma / 中华血液学杂志

Objective@#To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20+ B-cell non-Hodgkin’s lymphoma (NHL).@*Methods@#Nine patients with CD20+ B-cell NHL received dose-escalating IBI301 infusions (250 mg/m2, n=3; 375 mg/m2, n=3; 500 mg/m2, n=3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m2, 375 mg/m2, 500 mg/m2 dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events (AE). The ratios of CD19+, CD20+ B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics.@*Results@#Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m2 group, 14 events of AE in 375 mg/m2 group and 20 events of AE in 500 mg/m2 group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE (SAE) were reported. No dose-limiting toxicity (DLT) events were observed in the study. The ratio of CD20+ and CD19+ B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM.@*Conclusions@#The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients.@*Clinical trial registration@#Chinadrugtrials, CTR20140762.

New progress of anti-CD20 monoclonal antibody therapy for children with idiopathic refractory nephrotic syndrome / 医学研究生学报

Idiopathic Refractory Nephrotic Syndrome (IRNS) has been an intractable problem in clinical treatment .Anti CD20 monoclonal antibody is a new type of immunosuppressive agent , which can induce the lysis and apoptosis of B cells .Significant-ly, it improves the prognosis of IRNS patients .In recent years, a number of case studies and clinical trials have been conducted on the effectiveness of anti CD20 monoclonal antibody in the treatment of children with IRNS .In this paper, the mechanism, clinical applica-tion, adverse effects and problems in the study of anti CD 20 monoclonal antibody in IRNS will be reviewed .

A systematic review of low-dose rituximab monodonal antibody in the treatment of warm autoimmune hemolytic anemia / 基础医学与临床

Objective Standard dose of rituximab monodonal antibody(McAb)(375 mg/m2/week×4) has been recommended as a salvage regimen for refractory and recurrent warm autoimmune hemolytic anemia (wAIHA). The effect of low-dose rituximab in wAIHA needs more evaluation. Methods Through a compre-hensive literature search through PUBMED and CNKI databases, 13 articles of 172 cases were reviewed. Re-sults The current understanding of low-dose rituximab in wAIHA is limited. Based on the summary of these studies, the overall response rate was 87.8% with 62.8% complete response and 25% partial response. Since each study only enrolled several cases, the relapse rates markedly varied from 0 to 62.5%. Nevertheless, re-treatment of low-dose rituximab was still effective in some relapsed patients. No significant adverse event was reported. Conclusions Present literature analysis suggests that low-dose rituximab could be an effective and safe therapy for wAIHA.

A systematic review of low-dose rituximab monodonal antibody in the treatment of warm autoimmune hemolytic anemia / 基础医学与临床

Objective Standard dose of rituximab monodonal antibody(McAb)(375 mg/m2/week×4) has been recommended as a salvage regimen for refractory and recurrent warm autoimmune hemolytic anemia (wAIHA). The effect of low-dose rituximab in wAIHA needs more evaluation. Methods Through a compre-hensive literature search through PUBMED and CNKI databases, 13 articles of 172 cases were reviewed. Re-sults The current understanding of low-dose rituximab in wAIHA is limited. Based on the summary of these studies, the overall response rate was 87.8% with 62.8% complete response and 25% partial response. Since each study only enrolled several cases, the relapse rates markedly varied from 0 to 62.5%. Nevertheless, re-treatment of low-dose rituximab was still effective in some relapsed patients. No significant adverse event was reported. Conclusions Present literature analysis suggests that low-dose rituximab could be an effective and safe therapy for wAIHA.

Linfoma no hodgkiniano parecido al Burkitt / No hodgkin lymphoma burkitt-like

El linfoma no hodgkiniano parecido al Burkitt es considerado una neoplasia de células B altamente agresiva, con un alto índice de proliferación. Las presentaciones en forma de masas tumorales abdominales no son muy frecuentes y están poco documentadas en la literatura. Se reporta un caso poco usual de un paciente adulto joven con linfoma no hodgkiniano parecido al Burkitt, con infiltración del colon derecho, tratado con poliquimioterapia asociada a la administración de anticuerpo monoclonal anti-CD20, con lo que se alcanzó la remisión completa de la enfermedad. Posteriormente esta respuesta se consolidó con esquemas intensivos de quimioterapia y trasplante de progenitores hematopoyético autólogo. Actualmente se mantiene asintomático y sin tratamiento(AU)

The Burkitt-like lymphoma is considered a highly aggressive B-cell lymphoma, with a high proliferative rate. Presentation with extensive mass intestinal involvement is rare and poorly documented in the literature. We report the case of a young adult with the Burkitt-like lymphoma, and presenting extensive infiltration of the right colon, who receives chemotherapy treatment associated with administration of anti-CD20 monoclonal antibody, achieves complete remission of the illness and consolidation with intensive chemotherapy with autologous stem cell transplantation. Currently the patient is asymptomatic and without treatment(AU)

The immunotherapy of thyroid associated ophthalmopathy / 中华内分泌代谢杂志

The treatment of thyroid associated ophthalmopathy (TAO) is still a worldwide problem.The conventional glucocorticoid therapy can not benefit all the patients.In recent years,new immunosuppressive agents,such as tumor necrosis factor inhibitors and anti-CD20 monoclonal antibody have been emerging and serving as new targets in treating TAO to remedy the insufficiency of glucocorticoid treatment.In this paper,recent advances in immunotherapy of thyroid associated ophthalmopathy are reviewed.

Comparison of Two Quantitative Assays for Determination of Rh-anti-CD20 zumab and Their Application to Pharmacokinetic Study / 分析化学

An enzyme linked immunosorbent assay ( ELISA ) and a flow cytometry assay ( FCA ) based on Wil2-S cells were developed and systematically compared for quantification of recombinant anti-CD20 humanized monoclonal antibody ( rh-anti-CD20zumab) in biological matrix. The specificity, precision and accuracy of each method at correspondingly different linear range showed good results. For ELISA, the precisions of intra-day and inter-day were both <19 . 5%, the relative error was from-18 . 2% to 17 . 6%;For FCA, the precisions of intra-day and inter-day were both <19. 0%, the relative error was from -18. 9% to 18. 4%. The sensitivity of ELISA was significantly higher than that of FCA. The quantitative ranges of ELISA and FCA methods were 0. 04-5. 0 mg/L and 3. 1-200 mg/L, respectively. The concentrations in serum samples and pharmacokinetics analysis were determined by both of two methods after vein drip administration of rh-anti-CD20zumab in rhesus monkeys. Pharmacokinetics data showed that there was excellent consistency between results obtained by two methods at the given dose. We believe that the novel FCA with high speed and high sensitivity can be used to perform PK and PD study of cell surface antigen-targeted antibody derivatives.

Successful ABO Incompatible Adult Living Donor Liver Transplantation with New Simplified Protocol without Local Infusion Therapy and Splenectomy / 대한이식학회지

BACKGROUND: Since the time various strategies have been introduced to overcome the ABO-blood barrier including local infusion therapy (LIT), plasmapheresis and rituximab, the graft and patient survival outcome of ABO-incompatible (ABOi) adult living donor liver transplantation (ALDLT) has remarkably improved. But, the need for LIT under rituximab prophylaxis should be reevaluated because of high incidence of the LIT-related complications. The aim of this study was to verify the safety and efficacy of the protocol without local infusion therapy in ABOi ALDLT. METHODS: From November 2008 to December 2010, 43 cases of ABO-incompatible adult living donor liver transplantation were performed. In all cases, the spleen was preserved. From the 1st to 20th case, LIT was employed (group I, n=20). From the 21th case onwards, LIT was eliminated from the protocol (group II, n=23). The 3-month and 1-year patient and graft survival rates were compared between the two groups. The clinical parameters including recipient, donor and graft-related factors were also compared. The graft function was assessed in each group based on the serial changes in serum AST/ALT, total bilirubin and prothrombin time. RESULTS: There was 1 case of in-hospital mortality (2.3%) among the 43 cases. Overall 3-month and 1-year patient and graft survival rate was 97.7% and 92.1% during a mean period of 11.4 +/- 0.4 (0.9~28.9) months. There was no significant difference in the 3-month and 1-year patient and graft survival rates (95.0 vs. 100% and 90.0 vs. 92.9%, P=0.60) between groups. LIT-related complications occurred in 4 patients (20.0%). One case of antibody-mediated rejection occurred in group II. Both groups showed no difference in graft function at postoperative 3rd month. CONCLUSIONS: ABOi ALDLT without splenectomy and LIT resulted in promising outcomes. Therefore, LIT can be safely eliminated from the protocol.

Clinical study of autologous peripheral blood stem cell transplantation combined with anti-CD20 monoclonal antibody in non-Hodgkin lymphoma / 白血病·淋巴瘤

Objective To evaluate the efficacy of anti-CD20 monoclonal antibody (Rituximab) combined with autologous hematopoietic stem cell transplant (ASCT) in treatment of the patients with B cell non-Hodgkin lymphoma (NHL). Methods Twenty-one patients with B-cell NHL(CD20 positive) received ASCT with Rituximab at the dose of 385 mg·m-2·d-1 on day 1 and day 8 of mobilization,and day -1 and day +7 of conditioning regimen. Among the 21 patients receiving chemotherapy before the transplant, five cases achieved complete response (CR), eleven cases achieved partial remission (PR), and 5 cases had the progression of disease (PD) after many cycles of chemotherapy. Results The median follow-up was 24 months (1-68 months) in the present study. No relapse occurred among the 5 patients in CR before the transplant. Only one of the 11 PR patients relapsed 6 months post-transplantation. Three of the 5 PD patients died. Four of 21 cases (19 %) were documented as recurrence and death, the other 17 cases remained alive and disease-free. Both 2-year EFS and OS of these cases were 81%. No harmful effect of Rituximab was observed on the quality and quantity of collected stem cells as well as hematopoietic recovery post SCT. Conclusion The efficacy of ASCT with Rituximab in vivo purging in the patients with B-cell NHL was determined mainly by the disease status before transplant. The approach may be used as consolidation therapy to achieve long-term survival and increase the curable rate for patients in CR before transplant, and as intensification therapy to increase the remission rate and prolong the EFS and OS of the patients in PR. Rituximab did not show any adverse effect on collection and reconstitution of hematopoietic stem cells.

Effect of Anti-CD20 Monoclonal Antibody (Rituximab) on Recalcitrant Pemphigus Vulgaris / 대한피부과학회지

BACKGROUND: Pemphigus is a severe blistering disorder caused by autoantibodies to desmogleins 1 and 3. Because some patients with pemphigus never enter into remission, new immunosuppressants are warranted. Rituximab is a chimeric monoclonal antibody binding to the CD20 antigen on B cells, which proved to be effective in recalcitrant pemphigus. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of Rituximab in the treatment of refractory pemphigus vulgaris. METHODS: A retrospective analysis was conducted of six patients with recalcitrant pemphigus vulgaris in Yongdong Severance Hospital. Rituximab was administered intravenously at a dosage of 375 mg/m(2) body surface area. Five patient received 2 cycles of Rituximab treatment with an interval of 7 days. One patient received 5 cycles of treatment. The mean follow-up after treatment was 9.3 months (range, 2 months to 16 months). RESULTS: All the patients presented clinical improvements. The average pemphigus vulgaris severity score decreased from 12.2 to 2.5 after treatment. No adverse effects were observed. CONCLUSION: Rituximab has been proved as an effective and safe treatment for refractory pemphigus vulgaris.

Application of anti-CD20 monoclonal antibody in the treatment of active systemic lupus erythematosus / 基础医学与临床

To identify the clinical efficacy,immunological consequences and adverse effects of anti-CD20 monoclonal antibody in systemic lupus erythematosus.Nearly 100 patients have been reported and a 80% of them achieved marked reduction in global disease activity and clinical remission in lupus nephritis.Anti-CD20 monoclonal antibody is well tolerated in 90% of the patients,though10% of them had hypersensitivity reactions and 4 patients had severe opportunistic infection.