title: Risk assessment of relapse by lineage-specific monitoring of chimerism in children undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia.
abstract: Allogeneic hematopoietic stem cell transplantation is required as rescue therapy in about 20% of pediatric patients with acute lymphoblastic leukemia. However, the relapse rates are considerable, and relapse confers a poor outcome. Early assessment of the risk of relapse is therefore of paramount importance for the development of appropriate measures. We used the EuroChimerism approach to investigate the potential impact of lineage-specific chimerism testing for relapse-risk analysis in 162 pediatric patients with acute lymphoblastic leukemia after allogeneic stem cell transplantation in a multicenter study based on standardized transplantation protocols. Within a median observation time of 4.5 years, relapses have occurred in 41/162 patients at a median of 0.6 years after transplantation (range, 0.13-5.7 years). Prospective screening at defined consecutive time points revealed that reappearance of recipient-derived cells within the CD34(+) and CD8(+) cell subsets display the most significant association with the occurrence of relapses with hazard ratios of 5.2 (P=0.003) and 2.8 (P=0.008), respectively. The appearance of recipient cells after a period of pure donor chimerism in the CD34(+) and CD8(+) leukocyte subsets revealed dynamics indicative of a significantly elevated risk of relapse or imminent disease recurrence. Assessment of chimerism within these lineages can therefore provide complementary information for further diagnostic and, potentially, therapeutic purposes aiming at the prevention of overt relapse. This study was registered at clinical.
  
  
  
  gov with the number NC01423747.
authors: Children's Cancer Research Institute, Vienna, Austria.
authors: Sandra
authors: S
authors: Preuner
authors: St. Anna Children's Hospital, Vienna, Austria.
authors: Christina
authors: C
authors: Peters
authors: Children's Cancer Research Institute, Vienna, Austria.
authors: Ulrike
authors: U
authors: Pötschger
authors: Children's Cancer Research Institute, Vienna, Austria.
authors: Helga
authors: H
authors: Daxberger
authors: Children's Cancer Research Institute, Vienna, Austria.
authors: Gerhard
authors: G
authors: Fritsch
authors: Children's Cancer Research Institute, Vienna, Austria.
authors: Rene
authors: R
authors: Geyeregger
authors: University Medical Center Schleswig-Holstein and Christian-Albrechts-University Kiel, Department of Pediatrics, Kiel, Germany.
authors: André
authors: A
authors: Schrauder
authors: Charité, University Medicine Berlin, Germany.
authors: Arend
authors: A
authors: von Stackelberg
authors: University Medical Center Schleswig-Holstein and Christian-Albrechts-University Kiel, Department of Pediatrics, Kiel, Germany.
authors: Martin
authors: M
authors: Schrappe
authors: Johann Wolfgang Goethe University, Frankfurt, Germany.
authors: Peter
authors: P
authors: Bader
authors: Charité, University Medicine Berlin, Germany.
authors: Wolfram
authors: W
authors: Ebell
authors: Charité, University Medicine Berlin, Germany.
authors: Cornelia
authors: C
authors: Eckert
authors: University Hospital Tübingen, Germany.
authors: Peter
authors: P
authors: Lang
authors: Hannover Medical School, Hannover, Germany.
authors: Karl-Walter
authors: KW
authors: Sykora
authors: University Hospital UKE, Hamburg, Germany.
authors: Johanna
authors: J
authors: Schrum
authors: University Hospital Essen, Germany.
authors: Bernhard
authors: B
authors: Kremens
authors: University Children's Hospital Münster, Germany (current address: Medical University Greifswald, Germany).
authors: Karoline
authors: K
authors: Ehlert
authors: Dr. von Hauner University Children's Hospital, München, Germany.
authors: Michael H
authors: MH
authors: Albert
authors: University Hospital Düsseldorf, Germany.
authors: Roland
authors: R
authors: Meisel
authors: St. Anna Children's Hospital, Vienna, Austria.
authors: Anita
authors: A
authors: Lawitschka
authors: St. Anna Children's Hospital, Vienna, Austria.
authors: Georg
authors: G
authors: Mann
authors: Children's Cancer Research Institute, Vienna, Austria.
authors: Renate
authors: R
authors: Panzer-Grümayer
authors: University Children's Hospital Zürich, Division of Stem Cell Transplantation, Switzerland.
authors: Tayfun
authors: T
authors: Güngör
authors: Children's University Hospital Erlangen, Germany St. Anna Children's Hospital, Vienna, Austria Department of Pediatrics, Medical University Vienna, Austria.
authors: Wolfgang
authors: W
authors: Holter
authors: Pediatric Hematology and Oncology, University Medical Center Freiburg, Germany.
authors: Brigitte
authors: B
authors: Strahm
authors: University Hospital Jena, Germany.
authors: Bernd
authors: B
authors: Gruhn
authors: University Hospital Ulm, Germany.
authors: Ansgar
authors: A
authors: Schulz
authors: University Children's Hospital Giessen, Germany.
authors: Wilhelm
authors: W
authors: Woessmann
authors: Children's Cancer Research Institute, Vienna, Austria Department of Pediatrics, Medical University Vienna, Austria thomas.lion@ccri.at.
authors: Thomas
authors: T
authors: Lion
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000628:therapy*; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers