Variability in B-cell antigen expression: implications for the treatment of B-cell lymphomas and leukemias with monoclonal antibodies

Rossmann, Eva; Lundin, Jeanette; Lenkei, Rodiça; Mellstedt, Håkan; Österborg, Anders

doi:10.1038/sj.thj.6200119

Cited by 72 publications

(52 citation statements)

References 19 publications

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“…Fifteen blood samples were obtained on three separate occasions at Week 0, 3, and 6 from five patients with CLL in an indolent disease phase (3 males, 2 females, median age: 68 years, range 50-75, one patient with disease stage Rai 0 and two patients with Rai I and Rai II stage, respectively; four out of five patients without previous therapy). In addition, two consecutive samples obtained on Week 0 and 3 from seven patients with CLL (four males and three females, median age: 67 years, range 50-75, one patient with disease stage Rai 1, four patients with Rai II and two patients with Rai IV) receiving Interleukin-4 (IL-4) as experimental therapy were analyzed for CD20 expression (24,25). The control group included fourteen samples obtained on three separate occasions at 3 weeks intervals on Week 0, 3, and 6 (in one control only on two occasions) from five healthy donors (median 46 years, range 30-64).…”

Section: Blood Samplesmentioning

confidence: 99%

“…A consistent window of analysis was established and maintained with QC Windows using QC3 (FlowCytometryStandardsCorporation (FCSC), PuertoRico). The Quality Control of instrument included daily check up with Q-MESF (FCSC) and CaliBRITE TM beads (BDIS), and monthly check up with stabilized lymphocytes as previously described (25).…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

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Performance of calibration standards for antigen quantitation with flow cytometry in chronic lymphocytic leukemia

Rossmann

Lenkei

Lundin

et al. 2007

Cytometry Part B Clinical

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Background: The fluorescence intensities of CD3, CD4 on T cells and CD20, CD22 molecules on B cells were quantitatively measured on lymphocytes from chronic lymphocytic leukemia (CLL) patients and healthy donors.Methods: The performance of three different types of microbeads was compared, i.e. Quantum molecules of equivalent soluble fluorochrome (Q-MESF), Quantum simply cellular (QSC), and QuantiBRITE TM (QB). As all PE-conjugates had a F/P ratio of 1:1, the MESF units represented also the antibody binding capacity (ABC).Results: The ABCs of CD4 and CD20 antigens estimated with QSC (ABC QSC ) were higher than those assigned with QB (ABC QB ) with an average difference 49%. Higher numbers of antigenic sites were obtained with Q-MESF than with QSC for CD20 antigen. On the contrary, CD4 antigenic sites numbers estimated with QSC were higher than those estimated with Q-MESF. ABC values estimated with Quantum MESF PE (ABC Q-MESF ) were *15% higher than ABC QSC , whereas ABC Q-MESF was *49% higher than ABC QB INTRODUCTIONQuantitative measurements of fluorescence intensity by flow cytometry (QFCM) assess the numbers of monoclonal antibody (mAb) molecules bound to a cell. The fluorescence intensity (FI) of staining correlates to the number of fluorochrome conjugated mAb molecules bound to the cell, and consequently, the amount of receptors on the cell. Thus, the number of antigen receptors can be determined by QFCM, through estimation of the exact numbers of bound fluorescent antibody molecules, provided that appropriate standards and fluorescence controls are tested in parallel and reagents in saturating amounts are used. In addition, the process of quantitation facilitates standardization and quality control (1).

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Section: Blood Samplesmentioning

confidence: 99%

Section: Flow Cytometric Analysismentioning

confidence: 99%

Performance of calibration standards for antigen quantitation with flow cytometry in chronic lymphocytic leukemia

Rossmann

Lenkei

Lundin

et al. 2007

Cytometry Part B Clinical

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“…CD52 is a glycoprotein of unknown function that is highly expressed on cell surfaces of normal and malignant lymphocytes. 13 Binding of alemtuzumab to CD52 on lymphocytes induces complement-dependent cytotoxicity, 14,15 antibody-dependent cell-mediated cytotoxicity 14 and direct cytotoxicity (likely apoptotic cell death), [16][17][18] although a direct cytotoxic effect of alemtuzumab was not observed in other studies and therefore remains controversial. 19,20 Alemtuzumab received accelerated approval in the United States and Europe in 2001 for patients who had been treated with alkylating agents and in whom fludarabine therapy had failed.…”

Section: Introductionmentioning

confidence: 90%

Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia

Österborg

Foà

Bezares³

et al. 2009

Leukemia

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The consensus views of an expert roundtable meeting are presented as updated management guidelines for using alemtuzumab in chronic lymphocytic leukemia. Since the publication of previous management guidelines in 2004, clinical experience with alemtuzumab has grown significantly, especially regarding its efficacy and safety, management of cytomegalovirus (CMV) reactivation, identification of patient subgroups likely to benefit from alemtuzumab therapy and subcutaneous administration of alemtuzumab. The updated recommendations include (1) alemtuzumab monotherapy can be safely used as first-line therapy; (2) suitable patient subgroups for alemtuzumab therapy include elderly patients, patients with 17p deletion, patients with refractory autoimmune cytopenias and patients with profound pancytopenia at baseline due to heavily infiltrated bone marrow; (3) alemtuzumab treatment should be continued for 12 weeks (36 doses) whenever possible, and bone marrow examination may be considered at week 12 to evaluate response; (4) monitoring CMV reactivation by weekly PCR is mandated during therapy; when CMV reactivation becomes symptomatic or viremia increases, alemtuzumab therapy should be interrupted and anti-CMV therapy started; (5) subcutaneous administration is safe, easy to perform and appears equally effective compared with intravenous infusion and (6) our strong recommendation is that alemtuzumab combination therapy and consolidation therapy shall not be used outside carefully controlled clinical studies

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“…In reality, tissue-specific therapy will preferentially spare leukaemia cells, given their tendency towards dedifferentiation. For example, a number of CD20 receptors (one of the targets of immunotherapy) is 10 times lower on leukaemic cells than on normal B cells (Rossmann et al, 2001). Tissue-selective therapy exploits peculiarities of normal tissues: incorporation of iodine by thyroid tissue, dependence on androgens by prostate tissue, expression of CD20 by lymphocytes, just to name a few.…”

Section: Perspectives Of Tissue-selective Therapymentioning

confidence: 99%

Tissue-selective therapy of cancer

2003

Br J Cancer

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Variability in B-cell antigen expression: implications for the treatment of B-cell lymphomas and leukemias with monoclonal antibodies

Cited by 72 publications

References 19 publications

Performance of calibration standards for antigen quantitation with flow cytometry in chronic lymphocytic leukemia

Performance of calibration standards for antigen quantitation with flow cytometry in chronic lymphocytic leukemia

Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia

Tissue-selective therapy of cancer

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