title: Allogeneic Stem Cell Transplantation Improves Survival in Patients with Acute Myeloid Leukemia Characterized by a High Allelic Ratio of Mutant FLT3-ITD.
abstract: Allogeneic hematopoietic cell transplantation (alloHCT) as a postremission therapy in patients with FLT3-ITD-positive intermediate-risk acute myeloid leukemia (AML) remains controversial. FLT3-ITD mutations are heterogeneous with respect to allelic ratio, location, and length of the insertion, with a high mutant-to-wild-type ratio consistently associated with inferior prognosis. We retrospectively analyzed the role of alloHCT in first remission in relationship to the allelic ratio and presence or absence of nucleophosmin 1 mutations (NPM1) in the Study Alliance Leukemia AML2003 trial. FLT3-ITD mutations were detected in 209 patients and concomitant NPM1 mutations in 148 patients. Applying a predefined cutoff ratio of .8, AML was grouped into high- and low-ratio FLT3-ITD AML (HR(FLT3-ITD) and LR(FLT3-ITD)). Sixty-one patients (29%) were transplanted in first remission. Overall survival (OS) (HR, .3; 95% CI, .16 to .7; P = .004) and event-free survival (EFS) (HR, .4; 95% CI, .16 to .9; P = .02) were significantly increased in patients with HR(FLT3-ITD) AML who received alloHCT as consolidation treatment compared with patients who received consolidation chemotherapy. Patients with LR(FLT3-ITD) AML and wild-type NPM1 who received alloHCT in first remission had increased OS (HR, .3; 95% CI, .1 to .8; P = .02) and EFS (HR, .2; 95% CI, .1 to .8; P = .02), whereas alloHCT in first remission did not have a significant impact on OS and EFS in patients with LR(FLT3-ITD) AML and concomitant NPM1 mutation. In conclusion, our results provide additional evidence that alloHCT in first remission improves EFS and OS in patients with HR(FLT3-ITD) AML and in patients with LR(FLT3-ITD) AML and wild-type NPM1.
authors.affiliation: Medizinische Klinik und Poliklinik, Abteilung Innere Medizin V, Hämatologie, Onkologie und Rheumatologie, Universität Heidelberg, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Medizinische Klinik und Poliklinik I, TU Dresden, Dresden, Germany. Electronic address: johannes.schetelig@uniklinikum-dresden.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.affiliation: Medizinische Klinik und Poliklinik, Abteilung Innere Medizin V, Hämatologie, Onkologie und Rheumatologie, Universität Heidelberg, Heidelberg, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Bochtler
authors.affiliation: Medizinische Klinik und Poliklinik I, TU Dresden, Dresden, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schaich
authors.affiliation: Klinik für Innere Medizin 5, Schwerpunkt Onkologie/Hämatologie, Klinikum Nürnberg Nord, Universitätsklinik der Paracelsus Medizinischen Privatuniversität, Nürnberg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schäfer-Eckart
authors.affiliation: Klinik für Innere Medizin III, Klinikum Chemnitz gGmbH, Chemnitz, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hänel
authors.affiliation: Medizinische Klinik 5 - Hämatologie und Internistische Onkologie, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Wolf
authors.initials: W
authors.lastname: Rösler
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Abteilung für Hämatologie, Onkologie und Palliativmedizin, Robert-Bosch-Krankenhaus, Stuttgart, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kaufmann
authors.affiliation: Medizinische Klinik II, Universitätsklinikum Frankfurt Goethe-Universität, Frankfurt, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
authors.affiliation: Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.affiliation: Department of Hemato-Oncology, University Hospital Brno, CEITEC Masaryk University, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
authors.affiliation: Klinik und Poliklinik für Innere Medizin III, Universitätsklinikum Regensburg, Regensburg, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Reichle
authors.affiliation: Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Baldus
authors.affiliation: Abteilung für Hämatologie, Onkologie und Stammzelltransplantation, Asklepios Klinik St. Georg, Hamburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.affiliation: Medizinische Klinik und Poliklinik I, TU Dresden, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kramer
authors.affiliation: Medizinische Klinik und Poliklinik I, TU Dresden, Dresden, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röllig
authors.affiliation: Medizinische Klinik und Poliklinik I, TU Dresden, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Medizinische Klinik und Poliklinik I, TU Dresden, Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Medizinische Klinik und Poliklinik I, TU Dresden, Dresden, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D064591:Allografts; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D033581:Stem Cell Transplantation; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myeloid leukemia; Allogeneic transplantation; FLT3-ITD; NPM1 mutation