title: Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group.
abstract: OBJECTIVE
  In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT).
  
  
  METHODS
  In the Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10(-3) (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10(-3) (n = 109) continued to receive chemotherapy. MRD was quantified by real-time polymerase chain reaction for clone-specific T-cell receptor/immunoglobulin gene rearrangements.
  
  
  RESULTS
  The probability of event-free survival for patients with MRD ≥ 10(-3) was 64% ± 5% in ALL-REZ BFM 2002 compared with 18% ± 7% in the predecessor study ALL-REZ BFM P95/96 (P < .001). This was mainly achieved by reducing the cumulative incidence of subsequent relapse (CIR) at 8 years from 59% ± 9% to 27% ± 5% (P < .001). The favorable prognosis of patients with MRD less than 10(-3) could be confirmed in those with a late combined or isolated bone marrow B-cell precursor (BCP) -ALL relapse (CIR, 20% ± 5%), whereas patients with an early combined BCP-ALL relapse had an unfavorable outcome (CIR, 63% ± 13%; P < .001).
  
  
  CONCLUSIONS
  Allogeneic HSCT markedly improved the prognosis of patients with intermediate risk of relapse of ALL and unsatisfactory MRD response. As a result, outcomes in this group approximated those of patients with favorable MRD response. Patients with early combined relapse require treatment intensification even in case of favorable MRD response, demonstrating the prognostic impact of time to relapse.
authors.affiliation: Charité Universitätsmedizin Berlin, Department of Pediatric Oncology/Hematology, Augustenburger Platz 1, 13353 Berlin, Germany. cornelia.eckert@charite.de
authors.forename: Cornelia
authors.initials: C
authors.lastname: Eckert
authors.forename: Günter
authors.initials: G
authors.lastname: Henze
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Seeger
authors.forename: Nikola
authors.initials: N
authors.lastname: Hagedorn
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Renate
authors.initials: R
authors.lastname: Panzer-Grümayer
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: André
authors.initials: A
authors.lastname: Schrauder
authors.forename: Gabriele
authors.initials: G
authors.lastname: Escherich
authors.forename: Lucie
authors.initials: L
authors.lastname: Sramkova
authors.forename: Felix
authors.initials: F
authors.lastname: Niggli
authors.forename: Johann
authors.initials: J
authors.lastname: Hitzler
authors.forename: Arend
authors.initials: A
authors.lastname: von Stackelberg
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D012008:Recurrence; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome