title: Early MRD response as a prognostic factor in adult patients with acute lymphoblastic leukemia.
abstract: OBJECTIVE
  To evaluate the prognostic power of minimal residual disease (MRD) monitored by polymerase chain reaction at defined time points during early treatment in adult patients with acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  Seventy-one patients were treated according to the GMALL 07/2003 protocol and evaluated for MRD in bone marrow by specific clonal rearrangements of Ig/TCR in BCR-ABL negative ALL or fusion gene transcript in BCR-ABL positive ALL.
  
  
  RESULTS
  Three-year overall survival (OS) was 94% in patients with BCR-ABL negative ALL reaching complete molecular response (CMR) after the first course of chemotherapy (vs. 32% if MRD >10(-4) ; P = 0.001). Patients with CMR prior to the start of consolidation chemotherapy at week 11 had 3-yr OS 82% (vs. 18% if MRD >10(-4) ; P = 0.001). Patients with BCR-ABL positive ALL showed slower MRD dynamics. There was a trend to better OS in patients with ≥ 4 log reduction of BCR-ABL transcript prior to HSCT (92% vs. 50%; P = 0.065). None of the patients with detectable MRD (both BCR-ABL positive and negative) after HSCT survived 3 yr.
  
  
  CONCLUSIONS
  Early MRD kinetics is an important tool for new prognostication models with direct clinical impact irrespective of standard prognostic factors in patients with BCR-ABL negative ALL.
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Cyril
authors.initials: C
authors.lastname: Šálek
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: František
authors.initials: F
authors.lastname: Folber
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Froňková
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Bohumír
authors.initials: B
authors.lastname: Procházka
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Iuri
authors.initials: I
authors.lastname: Marinov
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Cetkovský
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Mayer
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015321:Gene Rearrangement; D019672:Genes, T-Cell Receptor; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007136:Immunoglobulins; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL; acute lymphoblastic leukemia; early response; immunoglobulin and T-cell receptor gene rearrangements; minimal residual disease; prognostic factors