title: [Molecular diagnosis and hematopoietic stem cell transplantation in 17 children with inherited bone marrow failure syndrome].
abstract: OBJECTIVE
  To enrich our national database with data of rare diseases by analyzing molecular diagnosis and hematopoietic stem cell transplantation (HSCT) in children with inherited bone marrow failure syndromes (IBMFS).
  
  
  METHODS
  Next-generation sequencing (NGS)-based genetic diagnosis panel was applied for the clinical diagnosis and management of IBMFS. Retrospective analysis was performed on clinical and genetic data of 17 consecutive children who received HSCT over a long time interval (November. 2005-June 2015).
  
  
  RESULTS
  Three patients were diagnosed only by clinical manifestation before 2012. After that NGS-based genetic diagnosis panel was used to identify IBMFS-related genes in 12/14.IBMFS patients (except two Diamond-Blackfan anemia (DBA) patients). Two Fanconi anemia (FA) patients were confirmed to be new variations through family-genotype-analysis and 3 families accepted prenatal diagnosis to avoid birth of affected fetuses. Seventeen IBMFS patients (10 FA,5 DBA and 2 dyskeratosis congenital (DKC)) were treated with HSCT from matched sibling donors (n=2), matched unrelated donors (n=8) or mismatched unrelated donors (n=7). The source of stem cells for transplantation included peripheral blood (n=12) and cord blood (n=5). With regard to the conditioning regimens, FA and DKC patients received fludarabine-based reduced intensity conditioning, while DBA patients received classical busulfan-based myeloablative conditioning. Median age at the time of HSCT was 36 months (7-156 months). The number of infused mononuclear cells and CD34⁺ cells was (10.6 ± 6.7) × 10⁸ and (5.9 ± 7.0) × 10⁶ per kilogram of recipient body weight, respectively. The median number of days to neutrophil recovery was 13 days after HSCT (range: 10-19 days). Platelet recovery was faster in the PBSCT group than in the CBT group ((16.3 ± 6.0) days vs. (30.0 ± 17.1) days,t=-2.487,P=0.026). During a median follow-up of 17 months (range: 2-114 months), except one FA patient who was transplanted with HLA-matched unrelated cord blood (CB) died from pneumonia and heart failure because of engraftment failure, other 16 children are alive after the successful HSCT. The failure-free survival rate of the patients three years after HSCT was 94%.
  
  
  CONCLUSIONS
  NGS-based molecular diagnosis technology and effective HSCT have significantly facilitated the treatment of children with IBMFS in our country, and our national database about this rare disease is to be further exploited.
authors.affiliation: Department of Hematology and Oncology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors.forename: Benshang
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors.forename: Changying
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Hematology and Oncology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology and Oncology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors.forename: Chengjuan
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Hematology and Oncology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Hematology and Oncology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Email: chenjing@scmc.com.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D000741:Anemia, Aplastic; D029503:Anemia, Diamond-Blackfan / Q000628:therapy; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D002648:Child; D019871:Dyskeratosis Congenita / Q000628:therapy; D005199:Fanconi Anemia / Q000628:therapy; D005312:Fetal Blood; D018380:Hematopoietic Stem Cell Transplantation; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D006801:Humans; D012189:Retrospective Studies; D035781:Siblings; D015996:Survival Rate; D019172:Transplantation Conditioning; D061349:Unrelated Donors; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D014740:Vidarabine; C024352:fludarabine