title: Prognostic impact of the CD34+/CD38- cell burden in patients with acute myeloid leukemia receiving allogeneic stem cell transplantation.
abstract: In acute myeloid leukemia (AML), leukemia-initiating cells exist within the CD34+/CD38- cell compartment. They are assumed to be more resistant to chemotherapy, enriched in minimal residual disease cell populations, and responsible for relapse. Here we evaluated clinical and biological associations and the prognostic impact of a high diagnostic CD34+/CD38- cell burden in 169 AML patients receiving an allogeneic stem cell transplantation in complete remission. Here, the therapeutic approach is mainly based on immunological graft-versus-leukemia effects. Percentage of bone marrow CD34+/CD38- cell burden at diagnosis was measured using flow cytometry and was highly variable (median 0.5%, range 0%-89% of all mononuclear cells). A high CD34+/CD38- cell burden at diagnosis associated with worse genetic risk and secondary AML. Patients with a high CD34+/CD38- cell burden had shorter relapse-free and overall survival which may be mediated by residual leukemia-initiating cells in the CD34+/CD38- cell population, escaping the graft-versus-leukemia effect after allogeneic transplantation. Evaluating the CD34+/CD38- cell burden at diagnosis may help to identify patients at high risk of relapse after allogeneic transplantation. Further studies to understand leukemia-initiating cell biology and develop targeting therapies to improve outcomes of AML patients are needed.
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Madlen
authors.initials: M
authors.lastname: Jentzsch
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Bill
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
authors.forename: Deedra
authors.initials: D
authors.lastname: Nicolet
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Leiblein
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Karoline
authors.initials: K
authors.lastname: Schubert
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Pless
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bergmann
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Wildenberger
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Luba
authors.initials: L
authors.lastname: Schuhmann
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Cross
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Pönisch
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Georg-Nikolaus
authors.initials: GN
authors.lastname: Franke
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Vladan
authors.initials: V
authors.lastname: Vucinic
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Thoralf
authors.initials: T
authors.lastname: Lange
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Behre
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.affiliation: Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Sebastian
authors.identifier: http://orcid.org/0000-0002-1315-2332
authors.initials: S
authors.lastname: Schwind
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis*; D000328:Adult; D000368:Aged; D064591:Allografts; D018952:Antigens, CD34 / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011379:Prognosis; D012008:Recurrence; D015996:Survival Rate; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D051997:ADP-ribosyl Cyclase 1