title: Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio.
abstract: Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1 and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148). Favorable overall survival (OS) was found for patients with mutated NPM1 without FLT3-ITD (71±4%). Outcome in patients with a high FLT3-ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23±8% and 12±6%, respectively. Patients with wild-type NPM1 without FLT3-ITD or with a low allelic burden of FLT3-ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P=0.022 and HR 0.50, P=0.004, respectively) or autoHSCT (HR 0.60, P=0.046 and HR 0.60, P=0.043, respectively). The lowest cumulative incidence of relapse (23±4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Versluis
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Laboratory medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: F E M
authors.initials: FE
authors.lastname: In 't Hout
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Devillier
authors.affiliation: HOVON Data Center, Erasmus University Medical Center Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands.
authors.forename: W L J
authors.initials: WL
authors.lastname: van Putten
authors.affiliation: Division of Hematology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: M G
authors.initials: MG
authors.lastname: Manz
authors.affiliation: Department of Hematology, Hôpital St Luc, Brussels, Belgium.
authors.forename: M-C
authors.initials: MC
authors.lastname: Vekemans
authors.affiliation: Department of Hematology, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: M-C
authors.initials: MC
authors.lastname: Legdeur
authors.affiliation: Stem Cell Transplant Team, University Hospital Basel, Basel, Switzerland.
authors.forename: J R
authors.initials: JR
authors.lastname: Passweg
authors.affiliation: Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Maertens
authors.affiliation: Department of Immunology and Hematology, University Medical Center, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kuball
authors.affiliation: Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: Biemond
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: P J M
authors.initials: PJ
authors.lastname: Valk
authors.affiliation: Department of Laboratory medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: B A
authors.initials: BA
authors.lastname: van der Reijden
authors.affiliation: Department of Cellular Biotechnologies and Hematology, 'Sapienza' University, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Meloni
authors.affiliation: Department of Hematology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: H C
authors.initials: HC
authors.lastname: Schouten
authors.affiliation: Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Vellenga
authors.affiliation: Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Pabst
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Willemze
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Ossenkoppele
authors.affiliation: Department of Hematology, University of Liège, Liège, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Baron
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Huls
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D057285:Precision Medicine / Q000379:methods; D012074:Remission Induction; D018570:Risk Assessment; D015996:Survival Rate; D020080:Tandem Repeat Sequences; D019172:Transplantation Conditioning / Q000379:methods; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3