Prognostic Impact of the CD34+/CD38- Cell Burden in Patients with Acute Myeloid Leukemia receiving Allogeneic Stem Cell Transplantation

Introduction: 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. Purpose: We evaluated clinical and biological associations and the prognostic impact of a high diagnostic CD34+/CD38- cell burden in AML patients receiving an allogeneic stem cell transplantation (HSCT) in complete remission. Here, the therapeutic approach is mainly based on immunological graft-versus-leukemia effects. Methods: Percentage of bone marrow CD34+/CD38- cell burden in 169 AML patients at diagnosis was measured using flow cytometry. The optimal cutoff of 6% was applied and used to evaluate the impact of a high CD34+/CD38- cell burden on outcome. Results: The CD34+/CD38- cell burden 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 HSCT. Conclusion: Evaluating the CD34+/CD38- cell burden at diagnosis may help to identify patients at high risk of relapse after allogeneic HSCT. Further studies to understand leukemia initiating cell biology and develop targeting therapies to improve outcomes of AML patients are needed.:Bibliographische Beschreibung / Bibliographic description 1 Einleitung / Introduction 2 Epidemiology and AML diagnosis 2 Therapeutic options in AML 3 Genetic risk classification for therapeutic decisions in AML 6 Immunophenotyping in AML 10 Leukemia Initiating Cells 11 Objectives of the here presented study 13 Publikation / Publication 14 Anlage / Supplemental Material 23 Zusammenfassung / Summary 48 Weiterführende Arbeiten / Future developments GPR56 as new LIC marker 52 Referenzen / References 55 Referenz der Publikation / Reference of the publication 60 Erklärung über die eigenständige Abfassung der Arbeit 61 Curriculum Vitae 62 Komplette Publikationsliste 65 Danksagung 7