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Biol Blood Marrow Transplant. 2014 Sep;20(9):1335-40. doi: 10.1016/j.bbmt.2014.04.030. Epub 2014 May 2.

Predictive value of circulating angiopoietin-2 for endothelial damage-related complications in allogeneic hematopoietic stem cell transplantation.

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Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address:
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.


Endothelial cell damage has been reported to be associated with noninfectious transplant-related complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among these, noninfectious transplant-related complications with endothelial cell damage (TRC-EC) include sinusoidal occlusive syndrome, transplant-associated microangiopathy, intestinal transplant-associated microangiopathy, capillary leak syndrome, idiopathic pneumonia syndrome, and diffuse alveolar hemorrhage. Because angiopoietin-2 (ANG2) plays an essential role in the endothelial cell damage of various inflammatory disorders, we hypothesized that ANG2 may also play a critical role in TRC-EC. We retrospectively estimated the incidence of TRC-EC and evaluated the association with ANG2 level at transplant. We studied 153 consecutive adult patients who underwent allo-HSCT at our institution between 2000 and 2012. Median patient age was 49 years (range, 16 to 68 years). With a median follow-up of 55 months, 3-year overall survival for all patients was 55%. The incidence of TRC-EC at day 100 was significantly higher in the high-ANG2 group (≥2000 pg/mL; n = 36) than in the low-ANG2 group (<2000 pg/mL; n = 117) (70% [95% confidence interval {CI}, 55% to 84%] versus 16% [95% CI, 11% to 24%]; P < .001). Multivariate analysis revealed that high ANG2 level at transplant was independently associated with higher risk of TRC-EC (hazard ratio, 6.01; 95% CI, 3.16 to 11.43; P < .001) and shorter overall survival (hazard ratio, 2.23; 95% CI, 1.66 to 4.48; P = .002). These results suggest that ANG2 level at transplant may be a useful marker for predicting the risk of TRC-EC after allo-HSCT. Prospective studies are warranted to validate our results.


Allogeneic hematopoietic stem cell transplantation; Angiopoietin-2; Capillary leak syndrome; Endothelial cell damage; Sinusoidal occlusive syndrome; Transplant-associated microangiopathy

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