| BackgroundAllogeneic hematopoietic stem cell transplantation(allo-HSCT)is an important or even the only potentially curative treatment for many hematological diseases.Severe acute graft-versus-host disease(a GVHD)is an extremely serious post-transplant complication with a very high mortality and a very poor prognosis.The first-line therapy for a GVHD is glucocorticoid such as methylprednisolone combined with immunosuppressive medicines such as cyclosporine,tacrolimus and so on,however,more than 50%of patients may still face first-line treatment failure.Besides,steroids and immunosuppressive medicines can also significantly increase the risk of infection and recurrence-related death in patients.Therefore,it is urgent to explore new treatment options for therapy refractory a GVHD(TR-a GVHD).Many studies have successively suggested that mesenchymal stem cells(MSC)has a unique negative immunomodulatory function and promoting hematopoietic reconstitution.The mechanism of how MSC treat a GVHD may be related to the above 2 effects especially the first one.However,the results of exiting studies are highly heterogeneous,and the actual efficacy in the real world is unknown.ObjectiveTo explore the efficacy and safety of human umbilical cord blood-derived mesenchymal stem cells(h UCB-MSCs)in the treatment of TR-a GVHD and the related factors for the efficacy.Methods1.We retrospectively analyzed the clinical data of 24 therapy-refractory a GVHD patients who accepted h UCB-MSCs infusions after allo-HSCT at Hematopoietic Stem Cell Transplantation Center,5th Ward,Department of Hematology,The First Affiliated Hospital of Zhengzhou University between January1,2017 and September 30,2020.2.Observation index:The overall response rate(ORR)and complete remission(CR)rate at day 28 after the first infusion of h UCB-MSCs and at the last follow-up(LFU)date,infusion-related adverse affects,primary disease recurrence and the2-year overall survival(OS).3.Statistical analysis:SPSS 25.0 software was used for data analysis.Fisher’s exact test was used to compare nominal variables.The Kaplan-Meier method was used to estimate survival rate and draw survival curves,and the Log-rank test was used to compare the group survival.The level of statistical significance was defined as P<0.05.Results1.The median dose of total infused h UCB-MSCs was 2.7×10~6/kg(range,(2.02-6)×10~6/kg)with a median of 2.5 infusions(range,2-6).The median time from the onset of a GVHD to first h UCB-MSCs infusion was 12.5 days(range,8-36).The ORR at day 28 after infusion was 83%(20/24).Of these,14patients had CR,4patients had partial remission(PR)and 2 patients had transient partial remission(t PR).The ORR at LFU date was 75%(18/24).Of these,14 patients had CR,4patients had PR.2.The probability of 2-year OS was 33.3%.The 2-year OS for patients achieving CR and PR/NR were 57%and 0%,respectively(P<0.0001).There was significant difference between these two groups.3.During the infusion of h UCB-MSCs and in the short term after infusion,there was no acute allergic reactions such as fever,rash and acute laryngeal edema,or infusion-related liver and kidney function injury occurred.At the end of the follow-up,the median follow-up time was 6.0 months(range,0.7-36.1 months),and there was no recurrence of primary disease or tumor associated with h UCB-MSCs occurred.4.Analysis of influencing factors related to curative effect:(1)From the analysis of age,there was no significant difference in the ORR at the LFU date between children and adults:100%vs.63%(P=0.066).(2)From the analysis of the TR-a GVHD scale,the ORR at the LFU date of grade II and grade III-IV TR-a GVHD were 100%and 57%,respectively(P=0.024).There were remarkable difference between them.(3)From the analysis of primary diseases,there was no significant difference in the ORR at the LFU date between malignant and non-malignant hematologic diseases:70%vs.100%(P=0.539).(4)From the analysis of involved organs,there was no significant difference in the ORR at the LFU date between a single involved organ group and 2 involved organs group:75%vs.75%(P=1.000).A total of 16 cases only involved a single organ,and the ORR at the LFU date of skin,gastrointestinal tract and liver were 100%,67%and 67%,respectively(P=0.467).There were no significant difference among them.(5)From the analysis of the number of infusions of h UCB-MSCs,there was no significant difference in the ORR at the LFU date between the number of infusions<4 times group and≥4 times group:67%vs.100%(P=0.27).ConclusionsIn conclusion,treatment with h UCB-MSCs is a safe and effective option for patients with TR-a GVHD. |
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