Bone Mesenchymal Stromal Cells For The Treatment Of Steroid-resistant Extensive Skin Chronic Graft-versus-host Disease

Objective:To evaluated the efficacy and safety of MSCs for the treatment of Steroid-resistant Extensive Skin Chronic Graft-versus-host Disease in prospective randomized study. To explore the factors associated with outcome and to provide the evidence for further therapy.Methods:24steroid-resistant extensive skin cGVHD patients, who had no improvement after conventional immunosuppressive therapy, were devided into2groups.16cases of the test group received both the initial immunosuppressive drug and the MSCs therapy, while the other8patients in control followed up until death or December31,2014. The response to the treatment and improvement of the cGVHD symptom were compare between two groups. The therapeutic results were evaluated according to the clinical standards.Results:In test group, the data of KPS calculated in1month,2months,3months,6 months,12months after the MSCs infusion were higher than the record before MSCs therapy,60.00±13.66.63.13±11.38.65.63±12.09,66.92±11.82.68.18±14.71vs58.75±12.58(P>0.05), and there was statistically significant difference in the KPS between3months after the MSCs infusion and before MSCs therapy. The data of BSA%calculated in1month,2months,3months,6months,12months after the MSCs infusion were smaller than the record before MSCs therapy,66.19±28.77、64.94±30.65.63.81±31.60,60.92±30.70.58.64±29.03vs68.88±30.03(P>0.05). and there was statistically significant difference among the BSA%in3months,6months,12months after the MSCs infusion against the the record before MSCs therapy. The data of MRS S calculated in1month,2months,3months,6months,12months after the MSCs infusion were lower than the record before MSCs therapy,20.00±11.25.18.62±10.72.18.06±9.25、16.38±8.69.15.82±9.78vs22.63±11.65, and there was statistically significant difference among the MRSS in6months,12months after the MSCs infusion against the the record before MSCs therapy. The total efficiency of the control group was25%(2/8); the total efficiency of experimental group was87.5%(14/16) and37.5%(6/16) of the patient reach partial remission. The results between test group and control group have statistically significant difference (P=0.04). Besides, no notable effect was found on overall survival (P=0.837), transplant-related mortality (P=0.837), relapse-free survival (P=0.837) between two groups. During the infusion of MSCs,1patient experience pulmonary infection,1patient experience varicella-zoster virus infection, one experience dental ulcer and one experience congestive rash, all of them were cured after symptomatic treatment. Till2014.12.31, there were3patient died due to transplant-related complications,2case in the test group while1case in the control group. There were no recurrence of the primary disease, diagnosis of malignant and non-malignant diseases, significant toxicity and allergic reactions. Conclusions:These results suggest that Mesenchymal stem cells to treat a wide range of skin refractory chronic graft-versus-host disease is an effective and safe therapy, but how long the MSCs can effect the body and appropriate infusion time, dose, route, etc. still need to explore further. MSCs may bring an application prospects for the clinic treatment of cGVHD.