Prognostic Factors Of Hematopoietic Stem Cell Transplantation For Pediatric Aplastic Anemia Patients

PART 1: Impact of anti-HLA antibodies on outcome of hematopoietic stem cell transplantation for pediatric aplastic anemia patientsObjective: Investigate the impact of anti-HLA antibodies on the outcome of hematopoietic stem cell transplantation for pediatric aplastic anemia patients,in order to promote the establishment of anti-HLA antibodies clinical system containing pre-transplantation antibody screening,donor selection,prognosis evaluation,intervention treatment and follow-up inspection,to improve the outcome of HSCT for pediatric aplastic anemia patients.Methods: This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic-HSCT at a single institution between Aug 2006 and May 2012 investigated the influence of anti-HLA antibodies on the outcome of HSCT.Serum samples collected before HSCT were tested for the presence of anti-HLA antibodies by luminex.Statistical analysis was perform to evaluate the correlation between HLA-antibodies and outcome of HSCT.Results: Pre-existing anti-HLA antibodies were detected in 54.9%(28/51)of patients,among whom 5.9%(3/51)had donor specific anti-HLA antibodies(DSHA).Anti-HLA antibodies were associated with worse 5-year survival(78.6% vs 100%,P=0.021)and higher treatment-related mortality(21.4% vs.0%,p=0.028)compared with antibody-negative patients.Presence of anti-HLA class I antibodies(P=0.024,RR 12.853,95% CI 1.397–118.234)and older age(P=0.027,RR 31.046,95% CI1.482–650.187)significantly increased the risk of post-HSCT mortality.No significant difference on graft failure rate was found between antibody positive and negative group(11.1% vs 4.3%,P=0.614).Conclusion: Pre-existing anti-HLA antibodies negatively affect the outcome of HSCT in pediatric aplastic anemia patients.Routine testing for anti-HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT to improve the outcome of HSCT.PART 2 Comparison of irradiation and non-irradiation conditioning regimen on the outcome of alternative donor hematopoietic stem cell transplantation for severe aplastic anemia: Meta-analysisObjective: Compare the impact of irradiation conditioning regimen and non-irradiation conditioning regimen on the outcome of alternative donor-hematopoietic stem cell transplantation(AD-HSCT)for severe aplastic anemia,in order to offer quantitative data for optimization of conditioning regime to improve the outcome of AD-HSCT.Methods: Medline,Embase,Cochrane library and CBM databases were searched(2000-2014)for relevant research articles,which were selected according to the study inclusion criteria.Quality assessment and data extraction were performed on the included studies.STATA 12.0 software was applied for META analysis.Results: Thirty-four clinical observational studies were included in the meta-analysis,containing 326 patients in the irradiation group and 345 patients in the non-irradiation group.Graft failure rate and overall survival of irradiation group were significantly lower than those of non-irradiation group(P<0.001,I~2=97.1%;P<0.001,I~2=63.9%).Graft failure rate and overall survival of low dose-irradiation group(200-400 c Gy)were significantly lower than those of non-irradiation group(P<0.001,I~2=97.2%;P=0.009,I~2=47.9%).In children,no significant difference was found between irradiation group and non-irradiation group on graft failure and overall survival(P=0.585,I~2=0.0%;P=0.147,I~2=35.5%).Conclusion: Irradiation conditioning regimen(low dose irradiation included)may reduce the risk of graft failure in AD-HSCT for severe aplastic anemia whereas without remarkable improvement of overall survival.Physicians should weigh the pros and cons with reference to the other risk factors of graft failure to make the individualized conditioning regimen.Non-irradiation conditioning regimen achieved comparable outcome to irradiation in children,which is recommended for AD-HSCT of pediatric aplastic anemia patients.Low dose irradiation conditioning regimen is recommended for HLA-mismatched transplantation and umbilical cord blood stem cell transplantation,which were associated with high risk of graft failure.