Successful Therapy with anti CD20 Monoclonal Antibody Rituximab in Patients with Acquired Hemophilia against Factor VIII

2006 ◽  
pp. 187-189
Author(s):  
M. Krause ◽  
Ch. von Auer ◽  
I. Stier-Brück ◽  
I. Scharrer
Keyword(s):  
Monoclonal Antibody ◽  
Factor Viii ◽  
Successful Therapy ◽  
Acquired Hemophilia ◽  
Anti Cd20

Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia

Blood ◽  
2004 ◽  
Vol 103 (12) ◽  
pp. 4424-4428 ◽  
Author(s):  
Roberto Stasi ◽  
Maurizio Brunetti ◽  
Elisa Stipa ◽  
Sergio Amadori
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Complete Response ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Acquired Hemophilia ◽  
Durable Response ◽  
Fviii Inhibitor ◽  
Fviii Activity ◽  
Anti Cd20

Abstract The activity and safety profile of selective B-cell depletion with rituximab, an anti-CD20 monoclonal antibody, were evaluated in 10 patients with acquired hemophilia. Rituximab was given intravenously at the dose of 375 mg/m2 once weekly for 4 consecutive weeks. Infusion-related side effects were observed in 3 patients but were of mild intensity and did not require discontinuation of treatment. Eight patients with Factor VIII (FVIII) inhibitor titers between 4 and 96 Bethesda units per milliliter (BU/mL) achieved a complete remission, which was defined as a return to normal FVIII activity and undetectable FVIII inhibitor titers. Two more patients with inhibitor levels greater than 100 BU/mL experienced only a partial transient decrease of the inhibitor after rituximab alone, but they achieved a complete response after being challenged with a combination of rituximab plus pulse intravenous cyclophosphamide. With a median follow-up of 28.5 months (range, 12-41 months), 3 patients have thus far relapsed. Retreatment with the monoclonal antibody at the same dose and schedule resulted in a new sustained response in all these patients. In conclusion, rituximab appears an effective and well-tolerated treatment for patients with acquired hemophilia and low inhibitor titers. A reinforcement of therapy with other agents seems to be required to achieve a full and durable response in those patients with high inhibitor levels. (Blood. 2004;103:4424-4428)

Pemphigus Vulgaris Associated with Acquired Hemophilia due to Factor VIII Inhibitor

2003 ◽  
Vol 65 (3) ◽  
pp. 223-226 ◽  
Author(s):  
Masahide YAMAGUCHI ◽  
Mamoru KOHDA ◽  
Hiroaki UEKI ◽  
Wataru FUJIMOTO
Keyword(s):  
Factor Viii ◽  
Pemphigus Vulgaris ◽  
Factor Viii Inhibitor ◽  
Acquired Hemophilia ◽  
Viii Inhibitor

A Factor VIII Neutralizing Monoclonal Antibody and a Human Inhibitor Alloantibody Recognizing Epitopes in the C2 Domain Inhibit Factor VIII Binding to von Willebrand Factor and to Phosphatidylserine

1993 ◽  
Vol 69 (03) ◽  
pp. 240-246 ◽  
Author(s):  
Midori Shima ◽  
Dorothea Scandella ◽  
Akira Yoshioka ◽  
Hiroaki Nakai ◽  
Ichiro Tanaka ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Amino Acid ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Light Chain ◽  
Amino Acid Residues ◽  
Amino Terminal ◽  
Neutralizing Monoclonal Antibody ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryA neutralizing monoclonal antibody, NMC-VIII/5, recognizing the 72 kDa thrombin-proteolytic fragment of factor VIII light chain was obtained. Binding of the antibody to immobilized factor VIII (FVIII) was completely blocked by a light chain-specific human alloantibody, TK, which inhibits FVIII activity. Immunoblotting analysis with a panel of recombinant protein fragments of the C2 domain deleted from the amino-terminal or the carboxy-terminal ends demonstrated binding of NMC-VIII/5 to an epitope located between amino acid residues 2170 and 2327. On the other hand, the epitope of the inhibitor alloantibody, TK, was localized to 64 amino acid residues from 2248 to 2312 using the same recombinant fragments. NMC-VIII/5 and TK inhibited FVIII binding to immobilized von Willebrand factor (vWF). The IC50 of NMC-VIII/5 for the inhibition of binding to vWF was 0.23 μg/ml for IgG and 0.2 μg/ml for F(ab)'2. This concentration was 100-fold lower than that of a monoclonal antibody NMC-VIII/10 which recognizes the amino acid residues 1675 to 1684 within the amino-terminal portion of the light chain. The IC50 of TK was 11 μg/ml by IgG and 6.3 μg/ml by F(ab)'2. Furthermore, NMC-VIII/5 and TK also inhibited FVIII binding to immobilized phosphatidylserine. The IC50 for inhibition of phospholipid binding of NMC-VIII/5 and TK (anti-FVIII inhibitor titer of 300 Bethesda units/mg of IgG) was 10 μg/ml.

scholarly journals Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 584-591 ◽  
Author(s):  
OW Press ◽  
F Appelbaum ◽  
JA Ledbetter ◽  
PJ Martin ◽  
J Zarling ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Lymph Node ◽  
B Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
B Cell Lymphomas ◽  
Antigenic Modulation ◽  
Minor Response ◽  
High Doses ◽  
Anti Cd20

Abstract Four patients with refractory malignant B cell lymphomas were treated with continuous intravenous (IV) infusions of murine monoclonal antibody (MoAb) 1F5 (anti-CD20) over five to ten days. Dose-dependent levels of free serum 1F5 were detected in all patients. Two patients had circulating tumor cells and in both cases 90% of malignant cells were eliminated from the blood stream within four hours of initiation of serotherapy. Antigenic modulation did not occur, and sustained reduction of circulating tumor cells was observed throughout the duration of the infusions. Serial bone marrow aspirations and lymph node biopsies were examined by immunoperoxidase and immunofluorescence techniques to ascertain MoAb penetration into extravascular sites. High doses (100 to 800 mg/m2/d and high serum 1F5 levels (13 to 190 micrograms/mL) were required to coat tumor cells in these compartments in contrast to the low doses that were adequate for depletion of circulating cells. Clinical response appeared to correlate with dose of MoAb administered with progressive disease (52 mg), stable disease (104 mg), minor response (1,032 mg), and partial response (2,380 mg) observed in consecutive patients. The patient treated with the highest 1F5 dose achieved a 90% reduction in evaluable lymph node disease, but the duration of this remission was brief (six weeks). This study demonstrates that high doses of 1F5 can be administered to patients with negligible toxicity by continuous infusion and that clinical responses can be obtained in patients given greater than 1 g of unmodified antibody over a ten-day period.

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