title: Predictive value of circulating angiopoietin-2 for endothelial damage-related complications in allogeneic hematopoietic stem cell transplantation.
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.
authors.affiliation: 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.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ueda
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Chihara
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kohno
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Tatekawa
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ozeki
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Watamoto
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Morishita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000378:metabolism*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D042702:Angiopoietin-2
keywords: Allogeneic hematopoietic stem cell transplantation; Angiopoietin-2; Capillary leak syndrome; Endothelial cell damage; Sinusoidal occlusive syndrome; Transplant-associated microangiopathy