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R-CHOP versus R-CVP in the treatment of follicular lymphoma: a meta-analysis and critical appraisal of current literature
Ganguly Siddhartha, Patel Vijay
Journal of Hematology & Oncology , 2009, DOI: 10.1186/1756-8722-2-14
Abstract: Two analyses were conducted: The first analysis compared R-CHOP to R-CVP as frontline agents for the treatment of FL, and the second analysis included both untreated and relapsed patients.For both studies, R-CVP was superior to R-CHOP when evaluating for complete response (CR). Odds ratios were 2.86 (95% CI, 1.81–4.51) in the first analysis and 1.48 (95% CI, 0.991–2.22) in the second analysis. However for overall response (CR+Partial response, PR), R-CHOP was superior, with odds ratios of 5.45 (95% CI: 2.51 – 11.83) and 5.54 (95% CI: 2.69 – 11.40), for the first and second analyses, respectively.R-CHOP and R-CVP protocols achieve excellent overall response. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive CR rate. In younger patients with FL where cumulative cardio-toxicity may be of importance in the long term and in whom future stem cell transplantation is an option, again R-CVP may be a more appealing option.Follicular lymphomas (FL) are for the most part indolent B-cell non-Hodgkin's lymphomas (B-NHL). Median survival is 9 to 11 years. Though FL initially responds to combination and single-agent chemotherapy, the disease ultimately relapses, with no plateau in the survival curve. While cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) [1] has been the initial chemotherapy of choice for patients with aggressive NHL, no such standard exists for patients with FL. Rituximab, a monoclonal antibody to CD20 antigen, is now commonly added to chemotherapy regimens for FL. Rituximab has been shown to have a favorable toxicity profile and to significantly increase time to progression (TTP) and response rates when used as a single agent in the treatment of symptomatic FL [2]. Given such encouraging results, Czuczman et al. treated FL patients with a combination of rituximab and CHOP (R-CHOP) [3]. Updated results showed that the overall response rate was 100%; with 87% of patients achieving a com
Ablation of the Proapoptotic Genes Chop or Ask1 Does Not Prevent or Delay Loss of Visual Function in a P23H Transgenic Mouse Model of Retinitis Pigmentosa  [PDF]
Adeseye Adekeye, Mohammad Haeri, Eduardo Solessio, Barry E. Knox
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0083871
Abstract: The P23H mutation in rhodopsin (RhoP23H) is a prevalent cause of autosomal dominant retinitis pigmentosa. We examined the role of the ER stress proteins, Chop and Ask1, in regulating the death of rod photoreceptors in a mouse line harboring the RhoP23H rhodopsin transgene (GHL+). We used knockout mice models to determine whether Chop and Ask1 regulate rod survival or retinal degeneration. Electrophysiological recordings showed similar retinal responses and sensitivities for GHL+, GHL+/Chop?/? and GHL+/Ask1?/? animals between 4–28 weeks, by which time all three mouse lines exhibited severe loss of retinal function. Histologically, ablation of Chop and Ask1 did not rescue photoreceptor loss in young animals. However, in older mice, a regional protective effect was observed in the central retina of GHL+/Chop?/? and GHL+/Ask1?/?, a region that was severely degenerated in GHL+ mice. Our results show that in the presence of the RhoP23H transgene, the rate of decline in retinal sensitivity is similar in Chop or Ask1 ablated and wild-type retinas, suggesting that these proteins do not play a major role during the acute phase of photoreceptor loss in GHL+ mice. Instead they may be involved in regulating secondary pathological responses such as inflammation that are upregulated during later stages of disease progression.
CD20 Expression in the Transplanted Kidney of Patients with Graft Loss and Transient Allograft Dysfunction
Yong Han, Bingyi Shi, Ming Cai, Xiaoguang Xu, Liang Xu, Qiang Wang, Wenqiang Zhou, Li Xiao
Journal of Medical Biochemistry , 2012, DOI: 10.2478/v10011-011-0037-z
Abstract: This study aimed to explore the relationship between the infiltration of CD20+ B cells and the survival time of a renal allograft and to investigate the role of infiltrated B cells in the rejection of the renal allograft. A total of 40 patients with renal allograft loss due to refractory rejection and 20 patients with transient renal allograft dysfunction were recruited. Renal biopsy was done and CD20 expression was detected by immunohistochemistry. In addition, the survival time of the renal allograft was also obtained. The relationships between the CD20 expression and the survival time of the renal allograft and graft loss due to rejection were analyzed. The associations of gender, age and clinicopathogical types with the CD20 expression were also investigated. The proportion of patients positive for CD20 in the transplanted kidney was higher in patients receiving nephrectomy of the allograft due to rejection than in those with transient allograft dysfunction. The diffuse infiltration of CD20+ B cells was considered as positive staining. In 40 samples from patients with graft loss, 19 had diffuse infiltration of CD20+ B cells (47.5%). In 19 patients positive for CD20, hyperacute rejection was found in 1 patient, acute rejection in 5 and chronic rejection in 13. Statistical analysis showed the CD20 expression was not associated with the age and gender of donors and recipients, regimen for immunosuppressive treatment, cold/warm ischemia time and secondary transplantation. CD20+ B cell infiltration predicts a poor prognosis of patients with kidney transplantation and is one of the risk factors of graft loss.
Distribution and force spectroscopy of CD20 antigen-antibody binding on the B cell surface
B 细胞膜CD20 抗原的分布与单分子力谱探测

Qiulan Wang,Yuhong Lu,Shengpu Li,Mu Wang,Jiye Cai,

生物工程学报 , 2011,
Abstract: The lower expression of CD20 antigen molecules on the B cell membrane is the primary characteristic of B-chronic lymphocytic leukemia (B-CLL). In this paper, we combined laser scanning confocal microscopy (LSCM) and quantum dots labeling to detect the expression and distribution of CD20 molecules on CD20+B lymphocyte surface. Simultaneously, we investigated the morphology and ultrastructure of the B lymphocytes that belonged to the normal persons and B-CLL patients through utilizing the atomic force microscope (AFM). In addition, we measured the force spectroscopy of CD20 antigen-antibody binding using the AFM tips modified with CD20 antibody. The fluorescent images indicated that the density of CD20 of normal CD20+B lymphocytes was much higher than that of B-CLL CD20+B cells. The AFM data show that ultrastructure of B-CLL CD20+B lymphocytes became more complicated. Moreover, the single molecular force spectroscopy data show that the special force of CD20 antigen-antibody was four times bigger than the nonspecific force between the naked AFM tip and cell surface. The force map showed that CD20 molecules distributed homogeneously on the normal CD20+B lymphocytes, whereas, the CD20 molecules distributed heterogenous on B-CLL CD20+B lymphocytes. Our data provide visualized evidence for the phenomenon of low-response to rituximab therapy on clinical. Meanwhile, AFM is possible to be a powerful tool for development and screening of drugs for pharmacology use.
Loss of CD20 Expression after Rituximab Therapy for B-Cell Lymphomas: A Review of the Literature  [cached]
Naoki Wada,Katsuyuki Aozasa
Cancer and Clinical Oncology , 2012, DOI: 10.5539/cco.v1n2p1
Abstract: Rituximab (Rx), a chimeric anti-human CD20 antibody, is used widely for the treatment of B-cell non-Hodgkin’s lymphomas (NHL) worldwide. Loss of CD20 expression in relapsed B-cell lymphomas after Rx treatment, however, is observed in some cases, which might be a cause of B-cell NHL unresponsiveness to Rx retreatment. The frequency of loss of CD20 expression after Rx treatment and radiotherapy, its correlation with histological changes, and its clinical implication together with possible molecular mechanisms are discussed in this review of pertinent literature. In high-grade B-cell NHL, loss of CD20 expression after Rx treatment was observed less frequently in Japan than in Australia. Evaluation of CD20 expression by immunohistochemical and flow cytometric methods is a reliable guide for employment of Rx treatment for B-cell lymphomas.
Blastomyces Antigen Detection for Monitoring Progression of Blastomycosis in a Pregnant Adolescent  [PDF]
Megan Tarr,John Marcinak,Kanokporn Mongkolrattanothai,Jennifer L. Burns,L. Joseph Wheat,Michelle Durkin,Mahmoud Ismail
Infectious Diseases in Obstetrics and Gynecology , 2007, DOI: 10.1155/2007/89059
Abstract: Although disseminated blastomycosis is a rare complication in pregnancy, delay in diagnosis and treatment can be fatal. We investigate the use of the Blastomyces urine antigen in diagnosis following disease progression in the intrapartum, postpartum, and neonatal periods. We describe a case of disseminated blastomycosis in a pregnant adolescent and review the pertinent literature regarding treatment and monitoring blastomycosis in pregnancy and the neonatal periods. This is the first reported case in which the Blastomyces urine antigen is utilized as a method of following disease activity during pregnancy confirming absence of clinically evident disease in a neonate. Urine antigen detection for blastomycosis can be useful for following progression of disease in patients with disseminated blastomycosis in both the intrapartum and postpartum periods.
Sustained Remission with Mogamulizumab in Peripheral T Cell Lymphoma with Aberrant CD20 Expression: Case Report and Literature Review  [PDF]
Kentaro Fukushima, Hiroshi Sata, Masami Imakita, Takahiro Karasuno
Journal of Cancer Therapy (JCT) , 2018, DOI: 10.4236/jct.2018.93018

A 82-year-old man presented with an enlarged multiple superficial lymph nodes. The histological diagnosis of lymph node was peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), with an aberrant expression of CD20. Generally, PTCL lacks B cell antigen such as CD19 or CD20, however, rare cases have been reported in the literature that showed PTCL patients expressing the B cell antigens. It is considered that the prognosis of CD20 positive PTCL is poor, however, standard therapy has not been established. He was treated with eight cycles of CHOP regimen, but the enlargement of a part of lymph nodes still remained. Recently, it is reported that C-C Chemokine receptor type 4 (CCR4) is known to be expressed about 50% case of PTCL and CCR4 target therapy is effective. Our case was positive for CCR4 so mogamulizumab (anti-CCR4 antibody) was administered. Consequently, dramatic response was obtained and its combination of these therapy resulted in complete remission for 24 months. This is the first case of sustained remission by administration of mogamulizumab against CCR4/CD20 double positive PTCL. This strategy may be benefit to obtain the good prognosis.

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma  [cached]
Xiao-Hui He,Bo Li,Sheng Yang,Ning Lu
Chinese Journal of Cancer , 2012, DOI: 10.5732/cjc.011.10420
Abstract: To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P = 0.001), Bcl-6-negative patients (P = 0.01), and MUM-1-positive patients (P = 0.003). The risk of disease relapse in patients with non-GCB subtype(P = 0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P = 0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity(P = 0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.
Impact of BMI and Gender on Outcomes in DLBCL Patients Treated with R-CHOP: A Pooled Study from the LYSA  [PDF]
Clémentine Sarkozy,Nicolas Mounier,Alain Delmer,Achiel Van Hoof,Jean Michel Karsenti,Emmanuel Fleck,Marie Maerevoet,Jean Claude Eisenmann,Richard Delarue,Michel Fabbro,Bertrand Coiffier
Lymphoma , 2014, DOI: 10.1155/2014/205215
Abstract: In diffuse large B-cell lymphoma (DLBCL), the age-adjusted International Prognostic Index (aaIPI) score is currently used to predict patient outcomes and to choose the best therapeutic treatment. Body mass index (BMI) and gender are occasionally sited as prognostic factors; however, their value has never been studied in a large series of patients included in prospective clinical trials in the rituximab era. To assess the impact of BMI and gender on OS and PFS independently of the aaIPI score, we pooled 985 patients that were prospectively included in GELA studies and uniformly treated with R-CHOP. Univariate analysis indicated that high aaIPI and male gender were associated with a worse PFS, whereas high (>25) or low (<18.5) BMI scores were not. High aaIPI score was the only factor predictive for OS. In a multivariate analysis, including aaIPI score, gender, BMI, and interaction between BMI and gender, aaIPI remained the strongest predictive factor, and BMI < 18.5 was significantly associated with a worse OS but not PFS. In conclusion, in the rituximab era, the aaIPI score remains the major predictor of outcome in DLBCL patients; however, male gender and low BMI seem to impact outcome. 1. Introduction DLBCL is the most frequent type of NHL. The outcome of DLBCL has been remarkably improved in younger as well as elderly patients by rituximab, a chimeric monoclonal antibody targeting the CD20 antigen. A recent update of randomised trials conducted by the GELA group and others evaluating the efficacy of rituximab in addition to CHOP or intensified CHOP (namely, ACVBP: 75?mg/m2 doxorubicin and 1200?mg/m2 cyclophosphamide on day 1; 2?mg/m2 vindesine and 10?mg bleomycin on days 1 and 5; and 60?mg/m2 prednisone on days 1–5) demonstrated that the benefit of rituximab is maintained over the years [1–7]. Currently, R-CHOP is the standard of care for patients with newly diagnosed DLBCL [8, 9]. The International Prognostic Index (IPI) is commonly used to predict patient outcome and to stratify patients into low- and high-risk groups to choose the appropriate therapeutic treatment [10]. The IPI is based on 5 characteristics, age, performance status (PS), lactic dehydrogenase (LDH) levels, Ann Arbor stage, and extranodal sites, and identifies 4 risk categories of patients with different predicted survival. A simplified score termed the age-adjusted IPI (aaIPI), based on the LDH level, Ann Arbor stage, and PS, has been developed and is widely used to direct therapeutic decision in both the younger and elderly patients. Recent epidemiologic data has confirmed that
Combining a CD20 Chimeric Antigen Receptor and an Inducible Caspase 9 Suicide Switch to Improve the Efficacy and Safety of T Cell Adoptive Immunotherapy for Lymphoma  [PDF]
Lihua E. Budde, Carolina Berger, Yukang Lin, Jinjuan Wang, Xubin Lin, Shani E. Frayo, Shaunda A. Brouns, David M. Spencer, Brian G. Till, Michael C. Jensen, Stanley R. Riddell, Oliver W. Press
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082742
Abstract: Modification of T cells with chimeric antigen receptors (CAR) has emerged as a promising treatment modality for human malignancies. Integration of co-stimulatory domains into CARs can augment the activation and function of genetically targeted T cells against tumors. However, the potential for insertional mutagenesis and toxicities due to the infused cells have made development of safe methods for removing transferred cells an important consideration. We have genetically modified human T cells with a lentiviral vector to express a CD20-CAR containing both CD28 and CD137 co-stimulatory domains, a “suicide gene” relying on inducible activation of caspase 9 (iC9), and a truncated CD19 selectable marker. Rapid expansion (2000 fold) of the transduced T cells was achieved in 28 days after stimulation with artificial antigen presenting cells. Transduced T cells exhibited effective CD20-specific cytotoxic activity in vitro and in a mouse xenograft tumor model. Activation of the iC9 suicide switch resulted in efficient removal of transduced T cells both in vitro and in vivo. Our work demonstrates the feasibility and promise of this approach for treating CD20+ malignancies in a safe and more efficient manner. A phase I clinical trial using this approach in patients with relapsed indolent B-NHL is planned.
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