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 Blood, 1 September 2008, Vol. 112, No. 5, pp. 2139-2148.
Prepublished online as a Blood First Edition Paper on May 15, 2008; DOI 10.1182/blood-2007-12-130021.

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TRANSPLANTATION

Angiopoietin-2 predicts disease-free survival after allogeneic stem cell transplantation in patients with high-risk myeloid malignancies

Philipp Kümpers*,1, Christian Koenecke*,1,2, Hartmut Hecker3, Julian Hellpap1, Rüdiger Horn1, Willem Verhagen4, Stefanie Buchholz1, Bernd Hertenstein1, Jürgen Krauter1, Matthias Eder1, Sascha David1, Gudrun Göhring5, Hermann Haller1, and Arnold Ganser1

1 Center for Internal Medicine, 2 Institute of Immunology, 3 Institute of Biometrics, 4 Institute of Virology, and 5 Institute of Cellular and Molecular Pathology, Hannover Medical School, Hannover, Germany

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.


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