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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.

Author information

1
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: ueda-ngy@umin.ac.jp.
2
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
3
Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.

Abstract

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.

KEYWORDS:

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

PMID:
24796281
DOI:
10.1016/j.bbmt.2014.04.030
[Indexed for MEDLINE]
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