Diagnosis And Hematopoietic Stem Cell Transplantation In Children With Inherited Bone Marrow Failure Syndromes

Objectives:The aim of this study was to analyze the clinical diagnosis and outcomes of hematolpoietic stem cell transplantation(HSCT)in children with inherited bone marrow failure syndromes(IBMFS).Methods:1.Clinical features,conditioning regimens and outcomes of HSCT in patients with IBMFS from Shanghai Children’s Medical Center were retrospectively reviewed.2.Four cases of dyskeratosis congenita(DKC)among 25 patients with IBMFS were discussed and analyzed in this part.3.All the literatures about HSCT on patients with DKC were searched through Pubmed,Embase,Web of Science,Wanfang,China Knowledge Network and Weibu database.The data was screened according to the standard of inclusion criteria.Meta analysis was conducted on HSCT of DKC from sibling and unrelated donors using Stata 12.0 software.Results:1.We report HSCT in 25 children with Fanconi anemia(FA,n=12),Diamond–Blackfan anemia(DBA,n=7)and dyskeratosis congenita(DKC,n=5)and Shwachman-Diamond syndrome(n=1)from Shanghai Children’s Medical Center.The graft source was peripheral blood stem cells(n=20)or cord blood stem cells(n=5).FA,DC and SDS patients received reduced-intensity conditioning,while DBA patients had myeloablative conditioning.The median numbers of infused mononuclear cells and CD34~+cells were 14.4×10~8/kg and 5.3×10~6/kg,respectively.The median time for neutrophil and platelet recovery was 12 and 17 days,respectively.There was one primary graft failure.During a median follow-up of 27 months(range,2–133 months),the overall survival in all patients was 95.8%.The incidence of gradeⅡ–Ⅲacute and chronic graft versus host disease(GVHD)was 29.2%and 16.7%,respectively.2.We report our experience in 4 children with DKC who underwent HSCT after a fludarabine-based reduced intensity conditioning.The graft source was unrelated peripheral blood stem cells.Two patients experienced gradeⅡ–Ⅲacute GVHD,and chronic GVHD was only observed in one patient.All four patients remained alive and transfusion-independent at the median follow-up of 23.5 months.Correction of previously existing physical defects was observed in one patients.3.Were included 6 reports(ours included),63 cases of HSCT in DKC in total.Meta-analysis showed that there was no significant difference in the incidence of acute and chronic GVHD,the rate of donor engraftment and the 3-year event-free survival rate between sibling and unrelated donors,but the former may have advantages over the latter on 5-year event-free survival rate.Conclusions:Choosing appropriate conditioning regimens based on the characteristics of disease is the key to successful allogeneic HSCT in children with IBMFS.The unrelated donor is an effective source of stem cells for DKC transplantation.