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 natalizurnab infusions (range: 2-9 infusions). Blood samples were taken 4 weeks following the last infusion. With a median proportion of 7.6 CD34(+) cells/mu L (range: 2.2-30.4 cells/mu L), these patients had a significantly higher (P = .003) amount of circulating CD34(+) cells compared with 5 healthy volunteers (median: 1.4/mu L; range: 0.6-2.4/mu L) and 5 untreated MS patients (median: 1.0/mu L; range: 0.5-1.7/mu L) (P = .001). Serial measurements in 4 patients receiving their first natalizumab infusion showed a maximal significant increase in circulating CD34(+) cells from 3.3/mu L (range: 1.6-4.8/mu L) to 10.4/mu L (range: 7.5-12.04/mu L) 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.