| Objective:To investigate the incidence,risk factors and prognosis of acute graft-versus-host disease(aGvHD)after single umbilical cord blood transplantation(UCBT),and to find potential serum biomarkers with predictive value through prospective study.Methods:This study consists of two sections.1.Clinical data of 234 patients with hematologic malignancies who received a single UCBT for the first time in Anhui Provincial Hospital from March 2018 to October 2019were retrospectively analyzed.All patients were treated with a myeloablative conditioning without antithymocyte globulin(ATG).The day of umbilical cord blood transfusion was defined as day 0 after transplantation.By observing the engraftment,occurrence of complications such as aGvHD and infection,we analyzed and compared the differences in demographics,grafts and engraftment characteristics between patients with gradeⅡ-ⅣaGvHD-and aGvHD+,aimed to find potential high-risk factors.In addition,the impact of the occurrence of aGvHD on overall survival(OS)and transplant related mortality(TRM)was studied.2.The onset of early complications was prospectively observed in 31 hematologic patients after receiving UCBT with myeloablative conditioning,and peripheral venous blood serum specimens were collected at day 0,7,14,21,and 28 after transplantation to determine changes in serum concentrations of sST2,REG3α,IL-6,IL-8,and TNFR1 by enzyme-linked immunosorbent assay,as well as the relationship with early complications after transplantation,mainly aGvHD.Results:1.Analysis of the incidence,high risk factors and prognosis of aGvHD after UCBT with myeloablative conditioning:Among the 234 patients receiving UCBT for hematological malignancies,134 males and 100 females,and the median age was 16(IQR,8-32)years old.The primary disease was predominantly acute leukemia(88.04%).A total of 106patients developed aGvHD,with a median onset of 21(IQR,16-29)days after transplantation.The cumulative incidence of skin and gastrointestinal aGvHD was23.1%(95%CI,17.9-28.7%)and 31.6%(95%CI,25.8-37.6%),respectively.The cumulative incidence of gradeⅡ-ⅣandⅢ-ⅣaGvHD were 32.5%(95%CI,26.6-38.5%)and 24.8%(95%CI,19.4-30.5%),respectively.Univariate analysis showed that patients with less than 7/8 human leukocyte antigen(HLA)matched(HR=2.348,P=0.012),higher infused total nucleated cells(HR=1.055,P=0.036)and CD34~+cells dose(HR=1.157,P=0.003)and PES(HR=2.052,P=0.011)had a higher incidence of gradeⅡ-ⅣaGvHD.Multivariate analysis showed that less than 7/8 HLA matched(HR=2.924,95%CI,1.389-6.154,P=0.005),higher CD34~+cell dose(>1.77×10~5/kg,HR=1.183,95%CI 1.045-1.338,P=0.008)and PES occurrence(HR=1.790,95%CI1.022-3.137,P=0.042)were independent risk factors for gradeⅡ-ⅣaGvHD.GradeⅢ-ⅣaGvHD was significantly associated with increased transplant-related mortality(P<0.001)and decreased overall survival(P<0.001)in patients.2.There was no significant difference in serum biomarker levels between PES-and PES+patients at each time point after UCBT(P>0.05).The serum sST2 and TNFR1levels in aGvHD+patients were higher than those in aGvHD-patients,and there was a statistically significant difference in D28 sST2(P=0.036).Serum sST2 and TNFR1concentrations were positively correlated at D0,D21 and D28,showing low correlation(r=0.458,P=0.019),moderate correlation(r=0.633,P=0.005)and high correlation(r=0.821,P=0.023),respectively.Conclusions:1.aGvHD is a common complication after UCBT without ATG myeloablative pretreatment,the skin and gastrointestinal tract are most involved.2.Less than 7/8 HLA matched,higher CD34~+cell dose(>1.77×10~5/kg)and PES occurrence were independent risk factors for gradeⅡ-ⅣaGvHD.3.GradeⅢ-ⅣaGvHD was significantly related to the increase in transplant-related mortality and the decrease in overall survival.4.At the early stage of myeloablative cord blood transplantation,the serum sST2 and TNFR1 levels in peripheral blood of patients were positively correlated.5.The increase of D28 sST2 level after transplantation is closely related to the occurrence of aGvHD. |
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