Co-Transplantation Haploidentical Mesenchymal Stem Cells and Hematoietic Stem Cells with Nonmyeloablative Condition for Treatment of Relapsed or Refractory Acute Leukaemia.

Background The major problems of haploidentical stem cell transplantation is severe graft versus host disease (GVHD) and graft rejection because of MHC barrier. Recently, some studies shown that mesenchymal stem cells (MSCs) which can be differentiat into various cells of MSCs origin has some good ability of immunosuppressive activity which may be used for enhance hematopoietic engraftment and lessen GVHD after transplant. So we desinged the protocole of co-transplantation haploiddentical MSCs and perpheral blood stem cell with nonmyeloablative conditions based on our past clinical trails of NST with HLA-march donor and haploid transplant experiment of Rhesus and want to improve the effective of haploidentical transplant in relapsed or refractory acute leukaemia

Methods Eleven parients(year range 8–33) with HLA-mismarch donor(3/6=6, 4/6=3,5/6=1) in relapsed or refractory acute leukaemia were received reduced toxicity condition(cyclophosphamide, fludarabine, anti-thymocyte gloubin, and low dose totol body irradiation(2.0GY) following a MSCs injection of bone marrow and perpheral blood stem cells with apheresis CS-3000 machine later 30 minutes. GVHD prophylaxis consisted of cyclosporine A, Mycophenolate mofetil(MMF) and CD25 antibodies.

Results All eleven patients passed smoothly the hematopoietic suppression stage and white blood cells and plate count was recovery normal in 11–15 days and 15–21 days after transplant. Eight patients get full donor chimerism(FDC) and three patients get mixed chimerism (MC) in which two patients converted to FDC in 28 days and 1 patient still remained of the MC after three months. In two patients the bone marrow derived MSCs cotained 5% donor MSCs in MSCs cultrued by STR-PCR on day +30, +60 and +90d after MSC infusion. Among the all of eleven patients, the incidence of aGVHD(grade I-II=4, and grade III=1) was 45.5%(n=5), the incidence of cGVHD was 27.3%(n=3) and leukaemia relapsed rate is 9.1%(n=1). Follow-up 3 to 18 months, survive rate of patients is 72.7%(n=8) and the following is continous.

Conclusions We conclude that co-transplantation haploiddentical MSCs and PBSCT with reduced toxicity condition is safe and effective. MSCs may play an very important rules in improving the donor engraftment and reduce the GVHD in haploidentical transplant.