title: Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group.
abstract: OBJECTIVE
  Minimal residual disease (MRD) before allogeneic stem-cell transplantation was shown to predict outcome in children with relapsed acute lymphoblastic leukemia (ALL) in retrospective analysis. To verify this, the Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster (ALL-REZ BFM) Study Group conducted a prospective trial.
  
  
  METHODS
  Between March 1999 and July 2005, 91 children with relapsed ALL treated according to the ALL-REZ BFM 96 or 2002 protocols and receiving stem-cell transplantation in >or= second remission were enrolled. MRD quantification was performed by real-time polymerase chain reaction using T-cell receptor and immunoglobulin gene rearrangements.
  
  
  RESULTS
  Probability of event-free survival (pEFS) and cumulative incidence of relapse (CIR) in 45 patients with MRD >or= 10(-4) leukemic cells was 0.27 and 0.57 compared with 0.60 and 0.13 in 46 patients with MRD less than 10(-4) leukemic cells (EFS, P = .004; CIR, P < .001). Intermediate-risk patients (strategic group S1) with MRD >or= 10(-4) leukemic cells (n = 14) had a pEFS of 0.20 and CIR of 0.73, whereas patients with MRD less than 10(-4) leukemic cells (n = 21) had a pEFS of 0.68 and CIR of 0.09 (EFS, P = .020; CIR, P < .001). High-risk patients (S3/4, third complete remission) who received transplantation with an MRD load of less than 10(-4) leukemic cells (n = 25) showed a pEFS and CRI of 0.53 and 0.18, respectively. In contrast, pEFS and CRI were 0.30 and 0.50 in patients who received transplantation with an MRD load of >or= 10(-4) leukemic cells. Multivariate Cox regression analysis revealed MRD as the only independent parameter predictive for EFS (P = .006).
  
  
  CONCLUSIONS
  MRD is an important predictor for post-transplantation outcome. As a result, new strategies with modified stem-cell transplantation procedures will be evaluated in ALL-BFM trials.
authors.affiliation: Children's Hospital of the JW Goethe University, Frankfurt, Main, Germany. peter.bader@kgu.de
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Hermann
authors.initials: H
authors.lastname: Kreyenberg
authors.forename: Günter H R
authors.initials: GH
authors.lastname: Henze
authors.forename: Cornelia
authors.initials: C
authors.lastname: Eckert
authors.forename: Miriam
authors.initials: M
authors.lastname: Reising
authors.forename: Andre
authors.initials: A
authors.lastname: Willasch
authors.forename: Andrea
authors.initials: A
authors.lastname: Barth
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Sykora
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Holter
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kabisch
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Arend
authors.initials: A
authors.lastname: von Stackelberg
mesh_terms: D000293:Adolescent; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D018365:Neoplasm, Residual / Q000401:mortality*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012008:Recurrence; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous