title: Detection of relapse after hematopoietic stem cell transplantation in childhood by monitoring of WT1 expression and chimerism.
abstract: OBJECTIVE
  The measurement of minimal residual disease after hematopoietic stem cell transplantation is crucial for the prevention of hematological relapses. But many methods are limited to certain groups of patients. We present a comparison of two markers which are universally applicable: WT1 expression and chimerism status.
  
  
  METHODS
  We analyzed 1,848 peripheral blood and bone marrow samples of 148 children, adolescents and young adults with malignant hematological diseases. Median follow-up time was 739 days after transplantation.
  
  
  RESULTS
  All patients suffering from hematological relapse showed high WT1 levels. Approximately half (51%) of the 37 relapses could have been detected early through an increase in WT1 expression. WT1 kinetics revealed to be more specific than single elevated WT1 levels (p < 0.05) and chimerism analysis (p < 0.05). Combined with chimerism analysis, 74% of relapses were detectable in advance. Elevated WT1 expression levels after transplantation reached the highest sensitivity (64.9%) as a single marker, although differences were not significant. When the dynamics of both markers as well as any elevated WT1 expression were taken into account, a sensitivity of 81.5% and a specificity of 83.7% were obtained.
  
  
  CONCLUSIONS
  Hence, we conclude that WT1 is a useful marker for monitoring of minimal residual disease after transplantation, if specific targets are not available. WT1 expression and chimerism status should be mutually evaluated to decide about immunotherapeutic interventions aimed at preventing morphological relapse.
authors.affiliation: Department of Pediatrics, Jena University Hospital, Kochstr. 2, 07745, Jena, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Woehlecke
authors.forename: Susan
authors.initials: S
authors.lastname: Wittig
authors.forename: Juliane
authors.initials: J
authors.lastname: Sanft
authors.forename: Hermann
authors.initials: H
authors.lastname: Kreyenberg
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016162:Genes, Wilms Tumor; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018365:Neoplasm, Residual; D012008:Recurrence; D055815:Young Adult