Analysis Of Causes Of Complications And Death After Hematopoietic Stem Cell Transplantation In Childhood

Hematopoietic stem cell transplantation(HSCT)is an effective curable treatment for quite a lot of diseases,such as refractory/recurrent acute leukemia,severe aplastic anemia,congenital anemia,immunodeficiency disease,genetic metabolic disease,and solid tumor in children.However,many factors results in the failure of HSCT which restrict the success of HSCT.This study analyzed the factors related to the death of HSCT in order to improve the outcome of HSCT.This study was divided into two parts,one part discussed the causes of death after HSCT in childhood,and another part explored the risk factors related to bronchiolitis obliterans syndrome in pediatric HSCT.Part I:Analysis of causes of death after hematopoietic stem cell transplantation in childhoodObjective:To analyze the factors related to the failure and death in pediatric HSCT.Methods:This study retrospectively analyzed the data of children who received HSCT in our hospital from October 2010 to December 2018,including 1 11 cases for acute lymphoblastic leukemia(ALL),111cases for acute myeloid leukemia(AML),68cases for aplastic anemia(AA),33cases for Wiskott-Aldrich syndrome(WAS),45cases for other malignant diseases and 29cases for other non-malignant diseases.The overall survival rate(OS),recurrence-realted mortality,transplant-related mortality(TRM),and the constituent ratio of causes of death in children with different diseases were calculated,factors related to failure and death were figured out.Results:The OS,recurrent mortality,and TRM were(79.9±2.1)%,(5.1 ± 1.3)%,and(15.8±1.9)%,respectively.In AML group,OS,recurrent mortality and TRM were(80.0±3.9)%,(5.6±2.4)%,and(15.2±4.6)%,respectively.21 patients died of HSCT,of which recurrent deaths accounted for 23.8%,transplant-related deaths accounted for 76.2%,graft-versus-host disease 50%,infection 37.6%,thrombotic microvascular disease 6.2%,and cardiotoxicity 6.2%.The OS,recurrent mortality,and TRM in ALL group were(72.7±4.7)%,(6.2±2.5)%,and(21.8±4.4)%,respectively,which were not significantly different from those in AML(P>0.05).A total of 27 patients died,of which recurrent deaths accounted for 22.2%,and transplant-related causes accounted for 77.8%,including 33.3%of graft-versus-host disease(GVHD),52.4%of infection,4.8%of hepatic veno-occlusive disease,and 9.5%of leakage syndrome.The OS of children with AA was(91.9 ± 3.5)%,and the TRM was(8.1 ± 3.5)%,including 60%of GVHD,20%of infection,and 20%of leakage syndrome.In WAS group,OS was(87.9±5.7)%,TRM was(12.1±5.7)%,and 4 cases died.Among the causes of transplant related death,infection accounted for 75%and renal failure accounted for 25%.In other malignant disease groups,OS,recurrent mortality and TRM were(68.8±7.4)%,(13.2±6.5)%,and(20.4±6.1)%,respectively,13 cases died,recurrent deaths accounted for 30.8%,transplant-related deaths accounted for 69.2%,GVHD,infection and leakage syndrome accounted for 66.7%,22.2%,and 11.1%.In other non-malignant disease groups,OS and TRM were(86.2±6.4)%and(10.7±5.8)%.respectively.4 cases died,recurrent deaths accounted for 25%,and transplant-related deaths accounted for 75%which included 33.3%of GVHD,33.3%of infection,and 33.3%of leakage syndrome.Univariate analysis identified that disease type,stem cell source,donor source,HLA matching,acute GVHD and chronic GVHD were the factors affecting survival.Multivariate analysis showed that disease type,stem cell source,acute GVHD and chronic GVHD were the risk factors of death.Conclusion:The mortality of HSCT in children with aplastic anemia was the lowest.Infection and GVHD were the main causes related to TRM in HSCT.Besides,relapse was also one main factor causing death in leukemia patients.The disease type,source of donor,acute GVHD and chronic GVHD were the risk factors of death of HSCT.Part II:Factors related to bronchiolitis obliterans syndrome in pediatric hematopoietic stem cell transplantationBackground and Objective:Chronic graft versus host disease(cGVHD)is the main complication in the late stage of transplantation.The long-term pulmonary non-infections' complication in cGVHD is bronchiolitis obliterans.This study retrospectively explored the risk factors of BOS children after undergoing hematopoietic stem cell transplantation(HSCT)in our hospital to improve the survival.Methods:This study retrospectively analyzed the data of children who received hematopoietic stem cell transplantation in our hospital from October 2010 to December 2018.The enrollment criteria of the study subj ects are:1.Non-autologous transplantation;2.The survival time after HSCT at least 100 days.The diagnosis of BOS was based on the revised standard of NIH in 2014.This study analyzed the overall survival,cumulative incidence of BOS and the pulmonary function.The risk factors of children with BOS were explored by statistics software.Results:By the end of follow-up time,29 patients(8.26%)developed BOS,including 11 males and 18 females,with a median age of 92 months(67-132 months).The median time of BOS was 10 months(8.5-20 months)after HSCT.The 1-year,2-year,and 3-year cumulative incidence of BOS was(6.0±1.3)%,(10.0±1.8)%,and(10.7±2.0)%,respectively.Among the 29 patients with BOS,28 cases were complicated with other parts of cGVHD before the onset of BOS.Patients with cGVHD,the 1-year,2-year,and 3-year cumulative incidence of BOS were(12.8±2.9)%,(23.0±4.0)%,and(24.4±4.2)%,respectively.Multivariate analysis showed that female patients,preceding cGVHD involved in other organs,and pulmonary infection within 100 years after transplantation were independent risk factors for BOS.The pulmonary function test of 21 cases showed that the percentage of FEV1 and FEV1/FVC were(51.0±22.3)%and(77.4±22.1)%,respectively.The OS of BOS group and non-BOS group were(72.5±9.9)%and(87.2±2.2)%,respectively.24 cases relapsed after transplantation,all of them were acute leukemia.The cumulative relapse rate in BOS group and non-BOS group was(6.9±4.7)%and(8.5±1.8)%,respectively.There was no significant difference between the two groups(P>0.05).Conclusion:BOS is a serious complication after HSCT,which affected the survival rate.At the time of diagnosis of BOS,most of the patients' pulmonary function had reached moderate to severe ventilatory dysfunction.Female patients,preceding cGVHD with other organs,and pulmonary infection within 100 years after transplantation were independent risk factors for BOS.