| BackgroundAt present,allo-genetic hematopoietic stem cell transplantation is still the only way to cure thalassemia major(TM)patients.But in fact,less than half of the patients can find matched sibling or unrelated donors.Umbilical cord blood stem cell is a potential source of stem cells because of their weak antigenic activity,low HLA matching requirements and low GVHD rate.However,the number of stem cells in umbilical cord blood is fewer,especially many TM children with iron overload before transplantation,which makes the transplantation of umbilical cord blood stem cells in thalassemia faces great challenges with low implantation rate and high transplant-related mortality(TMR).AimsIn order to increase the dose of stem cells,peripheral blood stem cells from same newborns and haploid peripheral blood stem cells(PB SC)from relatives were co-transplanted in sibling cord blood transplantation(CBT)and unrelated CBT respectively in TM.What are the effects of this strategy on promoting the implantation of sibling and unrelated umbilical cord blood stem cells in patients with thalassemia?And what are the differences of transplant-related complications between that two group?This paper was to compare the efficacy between sibling CBT and unrelated CBT and to analyze the factors affecting stem cells implantation and hematopoietic reconstruction.MethodsFrom Jan.2012 to Oct.2019,the clinical data of 76 children with TM who were first underwent cord blood stem cell transplantation was analyzed retrospectively.To Dec.31,2019,the median follow-up time was 53.5 months.The NF-08-TM protocol with CY+Bu+Flu+TT in conditioning was used for sibling CBT.Haploid PBSC combined unrelated CBT was carried out with NF-14-TM protocol added CY in day+3,day+4,followed infusion of unrelated cord blood in+6 day.The average infusion of cord blood mononuclear cells was 8.50×10^7(2.73-20.30×10^7),of which CD34+cells were 2.42×10^5(0.26-8.06×10^5).Unrelated cord blood mononuclear cells were 5.90×10^7(0.77-11.35×10^7),of which CD34+cells were 1.78×10^5(0.17-4.44×10^5).The number of haploid mononuclear cells was 27.70×10^8(8.80-63.18×10^8),and the number of CD34+cells was 16.77×10^6(0.29-73.56×10^6).Before transplantation,serum ferritin,liver and heart MRI-T2*were used to evaluate the level of iron overload.SPSS 20.0 software was used to analyze the subjects’ clinical characteristics,long-term survival rate,factors affecting umbilical cord blood implantation and related complications.ResultsTotal of 45 cases of sibling CBT and 31 cases of unrelated CBT combined with haploid PBSC and umbilical cord blood implantation were enrolled.Two of the 76 thalassemia children died,with an OS of 96.3±2.6%,TFS 93.8±3.1%;TMR was 3.7%.The OS of the sibling CBT group and the unrelated CBT group were 97.8±2.2%and 90.0±9.9%,P=0.586;Meanwhile TFS were 93.3±3.7%and 92.9±6.9%,P=0.589.There was no significant correlation between serum ferritin levels and stem cell implantation time and hematopoietic reconstruction time.Liver iron concentration(MRI-T2*)in the unrelated CBT group was significantly correlated with delayed implantation of stem cells and delayed reconstruction of platelets(P=0.013 and P=0.034).There was no significant correlation between the number of umbilical cord blood cells and stem cells implantation and hematopoietic reconstruction.There was no significant difference in the rate of delayed implantation of stem cells and granulocyte reconstruction between the unrelated CBT group and the sibling CBT group,but the rate of delayed platelet reconstruction in the unrelated CBT group was significantly higher than that in the sibling CBT group(P=0.002).The time of umbilical cord blood implantation in the unrelated CBT group was shorter than that in the sibling CBT group(24.32 days vs 37.67 days,P=0.058),but the platelet reconstruction in this group was slower than that in the sibling CBT group,with no statistically significant difference(59.87 days vs 41.17days,P=0.061).In the ferritin level,the platelet reconstruction time in the unrelated CBT group was significantly higher than that in the sibling CBT group(P=0.031).Logistic regression analysis showed that ferrimin,umbilical cord blood sources,dose of umbilical cord blood mononuclear cells and acute GVHD were not risk factors for delayed implantation of stem cells(over 30 days).The incidence of acute and chronic GVHD in the unrelated CBT group was significantly higher than that in the sibling CBT group(P<0.001 and P=0.034).There was no significant difference in the incidence of VOD between that two groups.The virus infection rate of the unrelated CBT group was significantly higher than that of the sibling CBT group(P=0.008).The infection of herpes simplex virus type I was common in sibling CBT,while cytomegalovirus was the main infectious virus in unrelated CBT.ConclusionBy increasing the dose of stem cells,the prognosis of TM after transplantation was favorable both in sibling and unrelated CBT group.Unrelated CBT combined with haploid PBSC can potentially reduce implantation time compared with sibling CBT.The strategies of prophylaxis and treatment of GVHD and cytomegalovirus infection should be strengthened.Iron overload may affect umbilical cord blood stem cell implantation and hematopoietic recovery. |
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