title: Pre-transplant Quantitative Determination of NPM1 Mutation Significantly Predicts Outcome of AIlogeneic Hematopoietic Stem Cell Transplantation in Patients with Normal Karyotype AML in Complete Remission.
abstract: Minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) before allogeneic hematopoietic stem cell transplantation (alloHSCT) can influence the results of therapy. With the aim of evaluating the potential role of pre-transplant MRD, we studied the impact of pre-transplant MRD level on the outcome of alloHSCT in patients with AML in complete remission (CR).
  
  
  
  From 2/2005 to 9/2014, 60 patients with a median age of 54 years (range=30-66 years) with normal karyotype-AML harboring nucleophosmin 1 (NPM1) mutation [53% Fms-related tyrosine kinase receptor 3 internal tandem duplication (FLT3/ITD)-positive] in first (n=45) or second (n=15) CR underwent myeloablative (n=16) or reduced-intensity (n=44) alloHSCT (27% related, 73% unrelated). The MRD level was determined from bone marrow samples using real-time polymerase chain reaction for detection of NPM1 mutations before starting the conditioning regimen.
  
  
  
  The estimated probabilities of 3-year relapse, event-free survival (EFS) and overall survival (OS) for the whole cohort were 28%, 54%, and 59%, respectively. Statistical analysis showed that only age over 63 years and high MRD level affected alloHSCT outcome. Pre-transplant MRD level of 10 mutant copies of NPM1 per 10,000 Abelson murine leukemia viral oncogene homolog 1 (ABL) copies had the strongest statistical significance, and detection of higher MRD level (>10 NPM1-mutant copies) before alloHSCT was associated with increased overall mortality (hazard ratio=3.71; 95% confidence interval=1.55-9.06; p=0.004). The estimated probabilities of 3-year relapse, EFS, and OS were 6%, 72%, and 75% for patients with a low level of MRD and 48%, 35%, and 40% for patients with a higher level.
  
  
  
  Our data showed that the pre-transplant level of MRD in patients with normal karyotype AML harboring NPM1 mutation in CR provides important prognostic information, which as an independent prognostic factor predicts transplant results.
authors: Department of Haematology and Oncology, Faculty Hospital Plzen, Plzen, Czech Republic karas@fnplzen.cz.
authors: Michal
authors: M
authors: Karas
authors: Department of Haematology and Oncology, Faculty Hospital Plzen, Plzen, Czech Republic.
authors: Katerina
authors: K
authors: Steinerova
authors: Department of Haematology and Oncology, Faculty Hospital Plzen, Plzen, Czech Republic.
authors: Daniel
authors: D
authors: Lysak
authors: Department of Haematology and Oncology, Faculty Hospital Plzen, Plzen, Czech Republic.
authors: Marcela
authors: M
authors: Hrabetova
authors: Department of Haematology and Oncology, Faculty Hospital Plzen, Plzen, Czech Republic.
authors: Alexandra
authors: A
authors: Jungova
authors: Department of Haematology and Oncology, Faculty Hospital Plzen, Plzen, Czech Republic.
authors: Jiri
authors: J
authors: Sramek
authors: Department of Haematology and Oncology, Faculty Hospital Plzen, Plzen, Czech Republic.
authors: Pavel
authors: P
authors: Jindra
authors: Biomedical Center, Faculty of Medicine in Plzen, Charles University Prague, Plzen, Czech Republic.|Department of Histology and Embryology, Faculty of Medicine in Plzen, Charles University Prague, Plzen, Czech Republic.
authors: Jiri
authors: J
authors: Polivka
authors: Biomedical Center, Faculty of Medicine in Plzen, Charles University Prague, Plzen, Czech Republic.
authors: Lubos
authors: L
authors: Holubec
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D057234:Preoperative Period; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin
keywords: Acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation; minimal residual disease; nucleophosmin 1 mutation