title: Hematopoietic cell transplantation in patients with intermediate and high-risk AML: results from the randomized Study Alliance Leukemia (SAL) AML 2003 trial.
abstract: The optimal timing of allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in first remission was offered also to patients with an FLT3-ITD (FMS-like tyrosine kinase 3-internal tandem duplication) allelic ratio >0.8, poor day +15 marrow blast clearance and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy. In the intent-to-treat (ITT) analysis, superiority of the experimental transplant strategy could not be shown with respect to overall survival (OS) or event-free survival. As-treated analyses suggest a profound effect of allogeneic HCT on OS (HR 0.73; P=0.002) and event-free survival (HR 0.67; P<0.001). In high-risk patients, OS was significantly improved after allogeneic HCT in aplasia (HR 0.64; P=0.046) and after HCT in remission (HR 0.74; P=0.03). Although superiority of one study arm could not be demonstrated in the ITT analysis, secondary analyses suggest that early allogeneic HCT is a promising strategy for patients with high-risk AML.
authors.affiliation: 1] Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany [2] DKMS, German Bone Marrow Donor Center, Dresden, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schetelig
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schaich
authors.affiliation: Städtisches Klinikum Nord, Medizinische Klinik 5, Nürnberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schäfer-Eckart
authors.affiliation: Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III, Chemnitz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hänel
authors.affiliation: Robert-Bosch-Krankenhaus, Abteilung für Hämatologie, Onkologie und Palliativmedizin, Stuttgart, Germany.
authors.forename: W E
authors.initials: WE
authors.lastname: Aulitzky
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Asklepios Klinik St Georg, Abteilung für Hämatologie, Onkologie und Stammzelltransplantation, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Schmitz
authors.affiliation: Universitätsklinikum Erlangen, Medizinische Klinik 5, Erlangen, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Rösler
authors.affiliation: Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster, Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stelljes
authors.affiliation: Charité Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: C D
authors.initials: CD
authors.lastname: Baldus
authors.affiliation: Medizinische Klinik und Poliklinik, Abteilung Innere Medizin V, Hämatologie, Onkologie und Rheumatologie, Universität Heidelberg, Heidelberg, Germany.
authors.forename: A D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Kliniken für Innere Medizin, Hämatologie/Onkologie und Immunologie, Universitätsklinikum Marburg, Marburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Neubauer
authors.affiliation: Medizinische Klinik II, Klinikum der J.W. Goethe Universität, Frankfurt, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Serve
authors.affiliation: Department of Hemato-Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Mayer
authors.affiliation: Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster, Münster, Germany.
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Mohr
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Oelschlägel
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Parmentier
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Röllig
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kramer
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Illmer
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3