title: Outcome of allogeneic stem cell transplantation in children with non-malignant diseases.
abstract: OBJECTIVE
  After allogeneic stem cell transplantation treatment failures are mostly caused by graft rejection or graft-versus-host disease (GVHD). T-cell depletion is an appropriate tool to prevent GvHD. However, it might be associated with an increased risk of graft rejection, which can be recognized by serial and quantitative characterization of chimerism. Thus, pre-emptive immunotherapy might be helpful to avoid graft rejection.
  
  
  METHODS
  We present the outcome of 56 transplants performed in 53 children with non-malignant diseases. T-cell depletion was conducted in 27/56 grafts. When increasing mixed chimerism over 30% autologous cells occurred low dose donor lymphocyte transfusions (DLT) were performed.
  
  
  RESULTS
  During the course of the follow-up 29 out of 53 patients achieved complete chimerism or low mixed chimerism (0-1%) and 28/29 remained in continuous complete remission. Donor engraftment failed in 2/53 patients who died of serious infection. Increasing mixed chimerism was found in 19 out of 56 transplantations. Fifteen of these 19 patients received additional immunotherapy with DLT. Eleven out of the 15 remained in complete remission. One of the 15 patients developed GvHD grade III that turned out to extensive chronic GvHD. The 3-year overall survival was 100% for patients transplanted from matched related or unrelated donors and 75% for patients transplanted from mismatched donors.
  
  
  CONCLUSIONS
  We demonstrated that children transplanted for non-malignant diseases have an excellent overall survival. T-cell depletion is associated with an increased risk of graft rejection. Pre-emptive immunotherapy with DLT, administered on the basis of increasing mixed chimerism, is feasible and might prevent graft rejection.
authors.affiliation: University Children's Hospital, Frankfurt, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Willasch
authors.forename: Walter
authors.initials: W
authors.lastname: Hoelle
authors.forename: Hermann
authors.initials: H
authors.lastname: Kreyenberg
authors.forename: Dietrich
authors.initials: D
authors.lastname: Niethammer
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: James F
authors.initials: JF
authors.lastname: Beck
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
mesh_terms: D002648:Child; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D008212:Lymphocyte Depletion; D011336:Probability; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology* / Q000379:methods; D016896:Treatment Outcome