Hematopoietic Stem/Progenitor Cells (HSPC) Mobilization Parameters in Patients Chronically Treated with the CD49d Blocking Antibody Natalizumab

Blockade of CD49d-mediated lymphocyte trafficking has been used therapeutically for certain autoimmune diseases. In addition to effects on mature lymphocytes, in mice and monkeys CD49d blockade also mobilizes immature hematopoietic cells from bone marrow (BM), capable of complete long-term engraftment despite a partial BM seeding defect. The aim of these studies was to ascertain effects on the biology of HSPC mobilization of single or chronic CD49d blockade in Multiple Sclerosis (MS) patients receiving disease-modifying treatment with the anti-functional anti-CD49d antibody, Natalizumab. These studies represent the first observations on HSPC mobilization by anti-CD49d antibodies in humans and on chronic exposure to a mobilizing agent. Circulating CD34+ cells (1.8±0.4/μL) and CFU-C (638±128/mL) were normal in MS patients (n=9) prior to the first Natalizumab infusion (normal controls: 1.3±0.1/μL CD34+ cells, 608±129/mL CFU-C). In chronically treated patients (i.e patients who had received ≥5 prior doses of Natalizumab) HSPC numbers were significantly elevated 30 days after the last infusion (CD34+ cells 9.0±1.2/μL, CFU-C 3243±332/mL, n=10, p