Cotransplantation of human umbilical cord mesenchymal and haplo-hematopoietic stem cells in patients with severe aplastic anemia.

To evaluate the efficacy and safety of cotransplantation of human umbilical cord mesenchymal stem cells (UC-MSCs) and haploidentical hematopoietic stem cells (HSCs) and to determine the correlation factors affecting incidence of graft versus host disease (GVHD) in patients with severe aplastic anemia (SAA), twenty-four SAA patients received haploidentical HSCs and UC-MSCs co-transplantation. Grafts came from a combination of granulocyte colony stimulating factor (G-CSF)-primed bone marrow and G-CSF mobilized peripheral blood stem cell of haploidentical donors, and in vitro expanded third-party donor derived UC-MSCs were employed as the cell graft. The conditioning regimens consisted of rabbit anti-human T-lymphocyte immunoglobulin (ATG), cyclophosphamide and fludarabine with or without busulfan. GVHD was prevented by using cyclosporine A (CSA), ATG, anti-CD25 monoclonal antibody and mycophenolate mofetil. All 24 patients achieved hematopoietic reconstitution. Median time to absolute neutrophil count >2 × 10(9)/L and platelet count >20 × 10(9)/L were 11 and 13 days, respectively. An incidence of 25 % on grade I-II acute GVHD was found while an incidence of 25 % of grade III-IV acute GVHD was seen. Blood type (r = 0.152, P = 0.043) and patient/donor pair (r = 0.541, P = 0.022) were significantly correlated with incidence of cGVHD. Transplantation related mortality was observed in 20.8 % of the cases. Co-transplantation of haploidentical HSCs and hUC-MSCs on SAA was an effective and safe approach in reducing GVHD and transplantation related mortality. The adequate conditioning regimen and early treatment for infection also played a critical role in the success of HSCT.