The monoclonal anti–VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans

Abstract

Abstract 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/μL (range: 2.2-30.4 cells/μL), these patients had a significantly higher (P = .003) amount of circulating CD34+ cells compared with 5 healthy volunteers (median: 1.4/μL; range: 0.6-2.4/μL) and 5 untreated MS patients (median: 1.0/μL; range: 0.5-1.7/μL) (P = .001). Serial measurements in 4 patients receiving their first natalizumab infusion showed a maximal significant increase in circulating CD34+ cells from 3.3/μL (range: 1.6-4.8/μL) to 10.4/μL (range: 7.5-12.04/μL) 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.