scholarly journals Adhesion to high endothelial venules: a model for dissemination mechanisms in non-Hodgkin's lymphoma

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 262-267 ◽  
Author(s):  
R Stauder ◽  
S Hamader ◽  
B Fasching ◽  
G Kemmler ◽  
J Thaler ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Lymphocytic Leukemia ◽  
Hodgkin's Lymphoma ◽  
Lymphoma Cells ◽  
High Endothelial Venules ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Human Lymphoma ◽  
Binet Stage

The interaction of human lymphoma cells with high endothelial venules (HEVs) on sections of lymphatic tissues was studied in 44 cases of non- Hodgkin's lymphoma (NHL) with the in vitro HEV binding assay. The relative adherence ratio (RAR) of lymphoma cells to HEVs as related to that of reactive lymphocytes was 0.29 to 4.64 in 38 cases of B chronic lymphocytic leukemia (CLL), 1.15 and 1.54 in two cases of immunocytic NHL, 1.12 and 0.70 in two cases of centrocytic NHL, 1.98 in one case of a peripheral T-NHL, whereas plasma cell leukemia cells adhered very weakly (RAR 0.1). Among the patients suffering from CLL a pronounced HEV binding ability of tumor cells correlated significantly with the more unfavorable Binet stages B and C (median 1.32) as well as with a widespread lymphatic dissemination, which strongly indicates a hematogenous, HEV-mediated spread (median 1.34). In contrast, weak adherence to HEVs was associated with Binet stage A (median 0.85; P < .05) and with a lacking or only localized clinical involvement of lymph nodes (median 0.84; P < .01). Thus, specific HEV recognition processes even operate in lymphoid neoplasms and via this mechanism seem to influence the dissemination of tumors.

Treatment with an Anti-C3b/iC3b Monoclonal Antibody as an Adjuvant to Rituximab Enhances the Killing of Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1402-1402
Author(s):  
Wu Peng ◽  
Xin Zhang ◽  
Juan Li ◽  
Giorgio Inghirami ◽  
Kenichi Takeshita ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hodgkin’S Lymphoma ◽  
Ex Vivo ◽  
Clinical Chemistry ◽  
Lymphocytic Leukemia ◽  
Hodgkin's Lymphoma ◽  
Complement C3 ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Complement-dependent cytotoxicity (CDC) is a key mechanism of Rituximab® (RTX) action in killing Non-Hodgkin’s Lymphoma (NHL) cells both in vitro and in vivo. Here we present studies of a mouse/human chimeric monoclonal antibody (Mab), ETI-210, specific for human complement C3 cleavage products C3b and iC3b, in enhancing RTX- mediated killing in vitro and ex vivo. Raji (NHL), primary NHL, and CLL cells were treated with RTX and ETI-210 in the presence of normal human serum (NHS) as a source of complement. Cell death was determined by propidium iodide staining or reduction of Alamar Blue®. After 1 hour of treatment, the killing of Raji cells by RTX plus ETI-210 plus NHS was observed to be 30–70% greater than that of RTX alone plus NHS by either detection method. The enhancing effect of ETI-210 was also seen in longer-term treatment (1 – 2 days). The killing by RTX plus ETI-210 was much lower in the absence of NHS than in the presence of NHS. ETI-210 was also tested ex vivo against primary cells from 12 NHL and 9 CLL patients. In 5 NHL samples, ETI-210 significantly enhanced RTX-mediated killing; in the remaining samples RTX alone already caused killing above 90%. The Mab also increased RTX-mediated killing in 4 out of 9 CLL samples. A pilot study examining the safety of administrating ETI-210 (5 and 30 mg/kg) with or without RTX was performed in cynomolgus monkeys. There were no cardiovascular changes. Clinical chemistry (potassium, glucose, sodium), liver function (alkaline phosphatase, ALT, albumin, total protein), kidney function (BUN, creatine, serum electrolytes) and hematological parameters (CBC profile, hemoglobin, MCV, MCH, MCHC) were not changed significantly. There was a transient reduction in CH50 values in the 30mg/kg ETI-210 group, which was independent of RTX administration. Serum concentrations of C3 and C4 were not affected. Because, ETI-210, a chimeric anti-C3b/iC3b Mab, was able to substantially enhance RTX-mediated killing of lymphoma cells via complement-mediated lysis and did not cause toxicity in monkeys, ETI-210 is being developed as a therapeutic agent for NHL and CLL treatment.

GM1 Expression of Non-Hodgkins Lymphoma Determines Susceptibility to Rituximab Treatment.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 228-228
Author(s):  
Christian Meyer zum Bueschenfelde ◽  
Yvonne Feuerstacke ◽  
Katharina S. Goetze ◽  
Kathrin Schlolze ◽  
Christian Peschel
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Lymphocytic Leukemia ◽  
Hodgkin's Lymphoma ◽  
Membrane Microdomains ◽  
Individual Response ◽  
Synthesis Inhibitor ◽  
Lymphoma Cells ◽  
Cell Surface Molecule ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract The monoclonal antibody rituximab directed against the cell surface molecule CD20 of mature B cells has been proven to be successful in the treatment in a variety of B cell malignancies. However, resistance against rituximab occurs and there is no prognostic marker to predict individual response. Rituximab has been shown to induce cell killing via antibody dependent cytotoxicity (ADCC), complement dependent cytotoxicity (CDC) and the induction of apoptosis. However, the mechanism that renders rituximab so effective in vivo remains elusive as does the reason for treatment failure in a subgroup of patients. On the molecular level the function of rituximab has been associated with the partitioning of CD20 molecules to lipid microdomains. We now show that the extent of CD20 recruitment to lipid rafts correlates with response to rituximab. In addition, analyzing 11 different Non Hodgkin’s lymphoma cell lines we demonstrate that the expression of the raft associated sphingolipid GM1 on lymphoma cells is associated with the susceptibility to rituximab. Of note, lymphoma cells treated with the sphingolipid synthesis inhibitor PDMP exhibited reduced GM1 expression levels and showed impaired susceptibility to rituximab as compared to non treated lymphoma cells. Furthermore, analyzing the GM1 expression on lymphoma cells of 217 patients with various types of indolent Non-Hodgkin’s lymphoma, we demonstrate significantly different GM1 expression in various Non-Hodgkin’s lymphoma subtypes. Whereas chronic lymphocytic leukemia (CLL) cells have a low GM1 expression, marginal zone lymphoma (MZL) cells exhibit much higher levels. Differences were not only detected between various lymphoma subgroups but also within one lymphoma subtype. Interestingly, whereas CLL cells from patients with high GM1 expression responded to rituximab, patients with low GM1 expressing CLL cells did not. Similar results were observed analyzing lymphoma cells from patients with mantle cell lymphoma (MCL) suggesting that GM1 expression correlates with responsiveness to rituximab in further types of Non-Hodgkin’s lymphoma. Collectively, these data demonstrate the importance of membrane microdomains for the effect of rituximab and may offer a predictive factor for the responsiveness of lymphoma cells to rituximab.

scholarly journals Review of the Safety and Feasibility of Rapid Infusion of Rituximab

2010 ◽  
Vol 6 (2) ◽  
pp. 91-93 ◽  
Author(s):  
Jill Atmar
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Lymphocytic Leukemia ◽  
Hodgkin's Lymphoma ◽  
Standard Chemotherapy ◽  
Rapid Infusion ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Added to standard chemotherapy, rituximab improved survival in patients with non-Hodgkin's lymphoma; added to fludarabine-based regimens, it improved response and survival in patients with chronic B-cell lymphocytic leukemia.

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