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Efficacy Of Clinical Outcomes In Umbilial Cord Blood Stem Cell Transplantation Between Humam Leucocyte Antigen Matched And Mismatched In The Treatment Of Children With Hematological Diseases

Posted on:2019-11-29Degree:MasterType:Thesis
Country:ChinaCandidate:Z ZhaiFull Text:PDF
GTID:2394330545971881Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an important way to cure refractory hematological malignancies and immunodeficiency disease.Since the success of Cord Blood Transplantation(CBT)in the world in 1988 and the establishment and improvement of umbilical cord blood banks all over the world,umbilical cord blood transplantation has been widely used in the treatment of diseases in many countries,especially in Europe and America and Japan.World multi-center cases reported that unrelated HLA 1 to 2 locus mismatched CBT and unrelated HLA matched bone marrow transplantation has the same long-term efficacy and it identifies the status of CBT in child and adult hematopoietic stem cell transplantation.In this study,we retrospectively analyzed the clinical data of 62 children with cord blood transplantation in our hospital.The aim of this study was to compare the clinical outcomes between humam leucocyte antigen(HLA)matched(HLA-M)and HLA mismatched(HLA-mis)cord blood stem cell transplantation in the treatment of children with hematological diseases on overall survival(OS),event free survival(EFS),neutrophil engraftment,platelet engraftment,acute graft versus host disease(a GVHD),cytomegalovirus infection and transplantation-related mortality(TRM),to provide technical indicators for the selection of cord blood transplantation donor in children.Objective:To analyze the curative effect and prognosis of children with hematological diseases treated by HLA matched and HLA mismatched cord blood stem cell transplantation,and to provide technical indicators for the selection of cord blood transplantation donor in children.Method:Sixty-two children with hematological diseases were treated with unrelated cord blood transplantation,42 males and 20 females were enrolled in the Children's Hospital of Suzhou University from April 2011 to November 2017,with all cases used single umbilical cord blood transplantation.There were 40 cases of malignant hematologic disease,including 23 cases of acute myeloid leukemia(AML),12 cases of acute lymphoblastic leukemia(ALL),2 case of chronic myeloid leukemia(CML),3 cases of myelodysplastic syndrome(MDS)and 22 cases of non-maligance hematology disease,including 14 cases of Wiskott-Aldrich syndrome(WAS),3 cases of severe aplastic anemia(SAA),1 cases of Fanconi anemia(FA),severe combined immun deficiency(SCID)1 case,1 case of congenital immunodeficiency disease,1 case of congenital granulocyte deficiency,1 case of high Ig M syndrome.Low resolution HLA-A,B and DRB1 were performed on cord blood and recipients.The number of total nucleated cells in single cord blood transplantation is(0.58-28.98)x107/kg,the median of 6.84x107/kg;the number of CD34 + cells is(0.47-15.8)x105/kg,the median of 3.68x105/kg.The conditioning regimens was mainly modified with Maryland/cyclophosphamide(BU/CY)or total body irradiation/cyclophosphamide(TBI/CY).All receptors received enhanced combined immunosuppression of cyclosporin A(or tacrolimus),mycophenolate mofetil and methotrexate(Cs A+MMF+MTX)to prevent graft versus host disease(GVHD).Active prevention and treatment of other complications after transplantation.The follow-up period was November 31,2017,and the median follow-up was 22.7 months(2 days to 79 months).The effects of 62 cases of cord blood transplantation were analyzed retrospectively.The number of umbilical cord blood was divided into low resolution group of HLA-M of 6/6,HLA-mis of 5/6 and HLA-mis of 4/6.Then divided them again into high resolution group of HLA-M of 10/10,HLA-mis of 8-9/10 and HLA-mis of less than 8/10.Comparing the overall survival(OS),event free survival(EFS),neutrophil engraftment,platelet engraftment,acute graft versus host disease(a GVHD),cytomegalovirus infection and transplantation-related mortality(TRM)between those groups.Result:At the end of the follow-up period,12 of the 62 children died and the overall survival rate was 80.6% and at that time the overall survival rate was the same to the event free survival rate.The overall survival rate of HLA-M of 6/6,HLA-mis of 5/6 and HLA-mis of 4/6 was 87.0%(20/23)?77.1%(27/35)?75%(3/4),There was no significant difference between the three groups(P = 0.587),The overall survival rate of high resolution group HLA-M of 10/10,HLA-mis of 8-9/10 and less than 8/10 was 100%(9/9)?87.5%(21/24)?61.1%(11/18),which was statistically significant difference(P=0.032).The neutrophil engraftment rate of HLA-M of 6/6 was 95.6%(22/23),as HLA-mis of 5/6 88.6%(31/35),HLA-mis of 4/6 100%(4/4),There was no significant difference between the three groups(P=0.744).Into the group of 6/6,it was divided into high resolution of HLA-M of 10/10,HLA-mis of 8-9/10 and less than 8/10,the rate was 100%(9/9),90%(9/10),100%(2/2),and the result showed there was no significant difference between the three groups(P=1).Into the group of 5/6,it was divided into high resolution of HLA-mis of 8-9/10 and less than 8/10,and the rate was 100%(14/14),76.9%(10/13),was no difference(P=0.0978).The platelet engraftment rate of HLA-M of 6/6 was 91.3%(21/23),as HLA-mis of 5/6 82.8%(29/35),HLA-mis of 4/6 100%(4/4),There was no significant difference between the three groups(P=0.693).Into the group of 6/6,it was divided into high resolution of HLA-M of 10/10,HLA-mis of 8-9/10 and less than 8/10 the rate was 100%(9/9),90%(9/10),100%(2/2),the result showed there was no significant difference between the three groups(P=1).Into the group of 5/6,it was divided into high resolution of HLA-mis of 8-9/10 and less than 8/10,and the rate was 92.9%(13/14),69.2%(9/13),was no difference(P=0.165).The neutrophil engraftment time of HLA-M of 6/6 was 15.5 days,as HLA-mis of 5/6 was 16 days,HLA-mis of 4/6 was 15 days,There was no significant difference between the three groups(P=0.696).Into the group of 6/6,it was divided into high resolution of HLA-M of 10/10,HLA-mis of 8-9/10 and less than 8/10,the time was 15 days,14 days and 16.5days,the result showed there was no significant difference between the three groups(P=0.817).Into the group of 5/6,it was divided into high resolution of HLA-mis of 8-9/10 and less than 8/10,and the time was 16.5 days,16 days,was no difference(P=0.678).The platelet engraftment time of HLA-M of 6/6 was 30 days,as HLA-mis of 5/6 24 days,HLA-mis of 20.5 days,There was no significant difference between the three groups(P=0.68).Into the group of 6/6,it was divided into high resolution of HLA-M of 10/10,HLA-mis of 8-9/10 and less than 8/10 the time was 32 days,34 days and 25.5 days,the result showed there was no significant difference between the three groups(P=0.813).Into the group of 5/6,it was divided into high resolution of HLA-mis of 8-9/10 and less than 8/10,and the time both was 20 days,was no difference(P=0.946).The incidence of acute GVHD was 61.9%(13/21),62.1%(18/29)and 75%(3/4)in the three group of low resolution respectively.There was no significant difference between the three groups(P=0.913).Into the high resolution group of 6/6,the results were 44.4%(4/9),66.7%(6/9),100%(2/2)of HLA-M of 10/10,HLA-mis of 8-9/10 and less than 8/10,and was no difference(P=0.54).Into the group of 5/6,it was divided into high resolution of HLA-mis of 8-9/10 and less than 8/10,the rate was 61.5%(8/13)vs 64.3%(8/11)(P=1.00).CMV infection rate was 60.9%(14/23)in HLA-M of 6/6,65.7%(23/35)in HLA-mis of 5/6,50%(2/4)in HLA-mis of 4/6,was no difference(P=0.77).In high resolution group of HLA-M of 10/10,HLA-mis of 8-9/10 and less than 8/10,there was no significant difference between three groups(77.8%(7/9)vs 75%(18/24)vs 55.6%(10/18),P=0.378)).62 cases of total transplant-related mortality(TRM)was 19.4%,of which 13.0%(3/23)in HLA-M of 6/6,22.9%(8/35)in HLA-mis of 5/6,25%(1/4)in HLA-mis of 4/6,there was no significant difference between three groups(P=0.587).Into the high resolution group of 6/6,the results were 0%(0/9),20%(2/10),0%(0/2)of HLA-M of 10/10,HLA-mis of 8-9/10 and less than 8/10,and was no difference(P=0.571).Into the group of 5/6,it was divided into high resolution of HLA-mis of 8-9/10 and less than 8/10,the rate was 7.1%(1/14)vs 46.2%(6/13)(P=1.00),which was statistically significant difference(P=0.0329).Conclusion:(1)There was no significant difference in the engraftment rate,the incidence and the severity of a GVHD,CMV infection,transplantation-related mortality,overall survival rate between transplantation of HLA mismatched of 4-5/6 and HLA matched.(2)By the mismatched locis of HLA increased,transplant-related mortality(TRM)increased too.The technology of high resolution can help us to choose a better UCB donor.
Keywords/Search Tags:humam leucocyte antigen(HLA), umbilial cord blood stem cell transplantation(UCBT), children, hematological diseases, transplant-related mortality(TRM)
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