title: A Novel Diagnostic and Prognostic Biomarker Panel for Endothelial Cell Damage-Related Complications in Allogeneic Transplantation.
abstract: Noninfectious transplantation-related complications (TRCs), such as graft-versus-host disease or TRC with endothelial cell damage (TRC-EC), remain as the major obstacle for successful allogeneic hematopoietic cell transplantation (allo-HCT). However, the diagnosis and prognosis for the emergence of these complications are difficult to define during the early post allo-HCT period. Here, we tried to generate a novel diagnostic system for TRC-EC by analyzing 188 adult patients who received allo-HCT. Our study found that the peripheral blood levels of angiopoietin 2 (ANG2), C-reactive protein (CRP), D-dimer, and thrombomodulin (TM) at the onset of TRCs were significantly associated with the development of TRC-EC. We next developed a composite biomarker panel incorporating the risk values of ANG2, CRP, D-dimer, and TM at the onset of TRCs, which classified these patients into 3 risk groups: low, intermediate, and high risk. As a result, the panel was useful not only for the diagnosis of TRC-EC with high specificity and sensitivity, but also for the prediction of the patients' long-term outcome. The 5-year overall survival (OS) rates of patients in the low-, intermediate-, and high-risk groups since the occurrence from TRCs were 76.2%, 54.9%, and 26.9%, respectively, and the high-risk score was significantly associated with both poor OS (hazard ratio [HR], 5.60; 95% confidence interval [CI], 2.81 to 11.20; P < .01) and frequent nonrelapse mortality (HR, 19.75; 95% CI, 5.59 to 69.77; P < .01). Thus, the composite panel proposed in this study provides a powerful tool for the diagnosis of TRC-EC and for the prediction of survival for patients with TRC-EC after allo-HCT.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Aichi, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Tatekawa
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Aichi, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kohno
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Aichi, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ozeki
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Aichi, Japan; Department of Hematology, Komaki City Hospital, Aichi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Watamoto
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Aichi, Japan; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ueda
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Aichi, Japan; Department of Hematology and Oncology, Japanese Red Cross Nagoya Daini Hospital, Aichi, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Yokota
authors.affiliation: Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Teramukai
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: junkuro@koto.kpu-m.ac.jp.
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.affiliation: Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Aichi, Japan; Department of Internal Medicine, Seirei Hospital, Nagoya, Aichi, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Morishita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D042783:Endothelial Cells / Q000473:pathology*; D004730:Endothelium, Vascular / Q000293:injuries / Q000473:pathology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D018180:Thrombomodulin / Q000097:blood; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D018180:Thrombomodulin; C036309:fibrin fragment D; D002097:C-Reactive Protein
keywords: Allogeneic hematopoietic stem cell transplantation; Angiopoietin 2; Biomarkers; Endothelial cell damage; Sinusoidal occlusive syndrome; Transplantation-associated microangiopathy; Transplantation-related complications