title: Effect of stem cell source on long-term chimerism and event-free survival in children with primary immunodeficiency disorders after fludarabine and melphalan conditioning regimen.
abstract: Reduced-intensity conditioning (RIC) regimens are increasingly being used in the transplantation of patients with primary immunodeficiency disorders (PIDs), but there are no large studies looking at long-term lineage-specific chimerism.
  
  
  
  We sought to analyze long-term chimerism and event-free survival in children undergoing transplantation for PIDs using RIC with fludarabine and melphalan (Flu/Melph) and to study the effect of donor type and stem cell source.
  
  
  
  One hundred forty-two children underwent transplantation with RIC by using Flu/Melph and for PIDs by using bone marrow (n = 93) or peripheral blood stem cells (PBSCs; n = 49). Donors were matched unrelated donors (n = 72), mismatched unrelated donors (n = 37), matched sibling donors (n = 14), matched family donors (n = 12), and mismatched family donors (n = 7).
  
  
  
  Overall survival at a median follow-up of 7.5 years was 78%, irrespective of stem cell source or donor type. When bone marrow was used as the stem cell source, 26% of patients ended up with very low levels of donor chimerism (<10% donor), especially in the myeloid lineage. Event-free survival in this group was significantly lower compared with that in the rest of the group (25% vs 70%, P < .001). With the use of PBSCs, more than 90% of patients achieved complete donor chimerism or high-level mixed chimerism (>50% donor chimerism) in all lineages.
  
  
  
  On the basis of our experience, we would suggest that PBSCs should be the stem cell source of choice in children with PIDs undergoing transplantation with Flu/Melph RIC from a matched donor source. This is most likely to ensure sustained high-level donor chimerism.
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom. Electronic address: kanchan.rao@gosh.nhs.uk.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Adams
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom; Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Allwood
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom; Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Austen
authors.initials: A
authors.lastname: Worth
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Juliana
authors.initials: J
authors.lastname: Silva
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lucchini
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Chiesa
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom; Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Persis
authors.initials: P
authors.lastname: Amrolia
mesh_terms: D019070:Cell Lineage; D046528:Chimerism; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D007223:Infant; D007231:Infant, Newborn; D008558:Melphalan / Q000627:therapeutic use*; D033581:Stem Cell Transplantation / Q000592:standards*; D013234:Stem Cells / Q000166:cytology*; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan
keywords: Primary immunodeficiency disorder; chimerism; hematopoietic stem cell transplantation; lineage specific; reduced intensity