title: Pretransplant NPM1 MRD levels predict outcome after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia.
abstract: The objective was to evaluate the prognostic impact of pre-transplant minimal residual disease (MRD) as determined by real-time quantitative polymerase chain reaction in 67 adult NPM1-mutated acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-eight of the 67 patients had a FLT3-ITD (42%). Median age at transplantation was 54.7 years, median follow-up for survival from time of allografting was 4.9 years. At transplantation, 31 patients were in first, 20 in second complete remission (CR) and 16 had refractory disease (RD). Pre-transplant NPM1 MRD levels were measured in 39 CR patients. Overall survival (OS) for patients transplanted in CR was significantly longer as compared to patients with RD (P=0.004), irrespective of whether the patients were transplanted in first or second CR (P=0.74). There was a highly significant difference in OS after allogeneic HSCT between pre-transplant MRD-positive and MRD-negative patients (estimated 5-year OS rates of 40 vs 89%; P=0.007). Multivariable analyses on time to relapse and OS revealed pre-transplant NPM1 MRD levels >1% as an independent prognostic factor for poor survival after allogeneic HSCT, whereas FLT3-ITD had no impact. Notably, outcome of patients with pre-transplant NPM1 MRD positivity >1% was as poor as that of patients transplanted with RD.
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.|Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kayser
authors.affiliation: Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Benner
authors.affiliation: Department of Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Cancer Center Heilbronn-Franken, Heilbronn, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Martens
authors.affiliation: Cancer Center Heilbronn-Franken, Heilbronn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Huber
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Stadtherr
authors.affiliation: Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
authors.forename: J W G
authors.initials: JW
authors.lastname: Janssen
authors.affiliation: Department of Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Röllig
authors.affiliation: Department of Oncology, Hospital of Ludwigshafen, Ludwigshafen, Germany.
authors.forename: M J
authors.initials: MJ
authors.lastname: Uppenkamp
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.|Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Bochtler
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Hegenbart
authors.affiliation: Department of Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: A D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dreger
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.|Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Krämer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D014408:Biomarkers, Tumor; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D020440:Gene Duplication; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011300:Preoperative Care; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012091:Repetitive Sequences, Nucleic Acid; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3