Ex Vivo Mesenchymal Precursor Cell-Expanded Cord Blood Transplantation Following Reduced Intensity Conditioning Regimens Improves Time to Neutrophil Recovery

摘要

We previously showed the safety of using cord blood (CB) expanded ex vivo in cocultures with allogeneic mesenchymal precursor cells (MPC) after myeloablative conditioning with faster recovery of neutrophils and platelets compared with historical controls.Herein, we report the transplant outcomes of 27 patients with hematologic cancers who received one CB unit ex vivo expanded with MPCs in addition to an unmanipulated CB (MPC group) after reduced intensity conditioning (RIC). The results in this group were compared with 51 historical controls who received two unmanipulated CB units (control group). The analyses were stratified for two RIC treatment groups: 1) total body irradiation 200 cGy + cyclophosphamide + fludarabine) (TCF), and 2) Melphalan+ fludarabine (FM).Co-culture of CB with MPCs led to an expansion of total nucleated cells by a median factor of 12 and of CD34+ cells by a median factor of 49. In patients that engraftment occurred, the median time to neutrophil engraftment was 12 days in the MPC group, as compared with 16 days in controls (p= 0.02). The faster neutrophil engraftment was observed in both RIC groups. The cumulative incidence of neutrophil engraftment on day 26 was 75% with expansion versus 50% without expansion in patients who received FM as the RIC regimen (p=0.03). Incidence of neutrophil engraftment was comparable in MPC and control groups if treated with TCF (82% versus 79%, p=0.4).Transplantation of CB units expanded with MPCs is safe and effective with faster neutrophil engraftment even after RIC regimens.