The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans.
We investigated the role of adhesion molecule VLA-4 in CD34+ blood stem-cell mobilization. Therefore, we examined 20 patients with multiple sclerosis (MS) who were treated with the anti-VLA-4 antibody natalizumab. Treated patients had received a median number of 4 natalizumab infusions (range: 2-9 infusions). Blood samples were taken 4 weeks following the last infusion. With a median proportion of 7.6 CD34+ cells/microL (range: 2.2-30.4 cells/microL), these patients had a significantly higher (P=.003) amount of circulating CD34+ cells compared with 5 healthy volunteers (median: 1.4/microL; range: 0.6-2.4/microL) and 5 untreated MS patients (median: 1.0/microL; range: 0.5-1.7/microL) (P=.001). Serial measurements in 4 patients receiving their first natalizumab infusion showed a maximal significant increase in circulating CD34+ cells from 3.3/microL (range: 1.6-4.8/microL) to 10.4/microL (range: 7.5-12.04/microL) 72 hours following natalizumab infusion (P=.001), including pluripotent cells in colony-forming assays. This mobilizing ability of natalizumab might be useful for patients with poor response to granulocyte colony-stimulating factor (G-CSF)-based protocols.
Zohren
Fabian
F
Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine-University, Düsseldorf, Germany. fabian.zohren@med.uni-duesseldorf.de
Toutzaris
Diamandis
D
Klärner
Viola
V
Hartung
Hans-Peter
HP
Kieseier
Bernd
B
Haas
Rainer
R
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34; D003114:Colony-Forming Units Assay; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors; D007958:Leukocyte Count; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy; D000069442:Natalizumab; D039904:Pluripotent Stem Cells
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34; D039041:Integrin alpha4beta1; D000069442:Natalizumab; D016179:Granulocyte Colony-Stimulating Factor