title: Angiopoietin-2 predicts disease-free survival after allogeneic stem cell transplantation in patients with high-risk myeloid malignancies.
abstract: Emerging data suggest a critical role for bone marrow angiogenesis in hematologic malignancies. The angiopoietin/Tie ligand-receptor system is an essential regulator of this process. We evaluated whether circulating angiopoietin-2 (Ang-2) is a predictor for the probability of disease-free survival (DFS) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia or myelodysplastic syndrome. Ang-2 was measured by enzyme-linked immunosorbent assay in serum from 20 healthy controls and 90 patients with acute myeloid leukemia or myelodysplastic syndrome before conditioning for HSCT. Circulating Ang-2 was elevated in patients (median, 2.21 ng/mL; range, 0.18-48.84 ng/mL) compared with controls (median, 0.87 ng/mL; range, 0.27-4.51 ng/mL; P < .001). Multivariate analyses confirmed the independent prognostic impact of Ang-2 (hazard ratio [HR] = 2.46; 95% confidence interval [CI], 1.27-4.76, P = .005), percentage of bone marrow infiltration (HR = 1.14; 95% CI, 1.01-1.29, P = .033), and chemotherapy cycles before HSCT (HR = 1.38; 95% CI, 1.01-1.08, P = .048). Regression tree analysis detected optimal cutoff values for Ang-2 and recursively identified bone marrow blasts and Ang-2 as the best predictors for DFS. Because few predictors for DFS exist in the setting of allo-HSCT, Ang-2 may be used as a readily available powerful biomarker to pre-estimate DFS and may open new perspectives for risk-adapted treatment of high-risk myeloid malignancies.
authors.affiliation: Center for Internal Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kümpers
authors.forename: Christian
authors.initials: C
authors.lastname: Koenecke
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hecker
authors.forename: Julian
authors.initials: J
authors.lastname: Hellpap
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Horn
authors.forename: Willem
authors.initials: W
authors.lastname: Verhagen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Buchholz
authors.forename: Bernd
authors.initials: B
authors.lastname: Hertenstein
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Sascha
authors.initials: S
authors.lastname: David
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
mesh_terms: D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000235:genetics / Q000628:therapy*; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012044:Regression Analysis; D012307:Risk Factors; D014184:Transplantation, Homologous
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers