Title | Circulating angiogenic factors associated with response and survival in patients with acute graft-versus-host disease: results from Blood and Marrow Transplant Clinical Trials Network 0302 and 0802. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Holtan, SG, Verneris, MR, Schultz, KR, Newell, LF, Meyers, G, He, F, DeFor, TE, Vercellotti, GM, Slungaard, A, MacMillan, ML, Cooley, SA, Blazar, BR, Panoskaltsis-Mortari, A, Weisdorf, DJ |
Journal | Biol Blood Marrow Transplant |
Volume | 21 |
Issue | 6 |
Pagination | 1029-36 |
Date Published | 2015 Jun |
ISSN | 1523-6536 |
Keywords | Acute Disease, Adolescent, Adult, Aged, Angiopoietin-2, Antigens, CD, Biomarkers, Bone Marrow Transplantation, Child, Endoglin, Epidermal Growth Factor, Female, Follistatin, Graft vs Host Disease, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Male, Membrane Proteins, Middle Aged, Receptors, Cell Surface, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Vascular Endothelial Growth Factor A |
Abstract | Circulating angiogenic factors (AF) reflect tissue healing capacity, although some AF can also contribute to inflammation and are indicative of endothelial dysfunction. The AF milieu in acute graft-versus-host disease (aGVHD) has not been broadly characterized. We hypothesized that patients with abundant AF involved in repair/regeneration versus those mediating damage/inflammation would have improved outcomes. Circulating AF known predominantly for repair/regeneration (epidermal growth factor [EGF], fibroblast growth factor-1 and -2, heparin binding-EGF-like growth factor, and vascular endothelial growth factor-A [VEGF-A], -C, and -D) and for damage/inflammation (angiopoietin-2, endothelin-1, soluble endoglin [sEng], follistatin [FS], leptin, and placental growth factor [PlGF]) were measured in a discovery set of hematopoietic cell recipients with grade III and IV aGVHD and compared with controls, then validated in 2 aGVHD cohorts enrolled in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials 0302 (n = 105, serum) and 0802 (n = 158, plasma) versus controls without aGVHD (n = 53, serum). Levels of EGF and VEGF-A were lower than in controls at the onset of aGVHD in both trials and higher with complete response to first-line aGVHD therapy in CTN 0802. FS and PlGF were elevated in aGVHD measured in either serum or plasma. At day 28 after initial aGVHD therapy, elevated FS was an independent negative prognostic factor for survival in both cohorts (hazard ratio, 9.3 in CTN 0302; 2.8 in CTN 0802). These data suggest that circulating AF are associated with clinical outcomes after aGVHD and, thus, may contribute to both pathogenesis and recovery. |
DOI | 10.1016/j.bbmt.2015.02.018 |
Alternate Journal | Biol Blood Marrow Transplant |
PubMed ID | 25759146 |
PubMed Central ID | PMC4426052 |
Grant List | U10 HL069294 / HL / NHLBI NIH HHS / United States U10 HL109526 / HL / NHLBI NIH HHS / United States P30 CA77598 / CA / NCI NIH HHS / United States UG1 HL069286 / HL / NHLBI NIH HHS / United States P01CA111412 / CA / NCI NIH HHS / United States P30 CA077598 / CA / NCI NIH HHS / United States U10 HL069290 / HL / NHLBI NIH HHS / United States P01 CA065493 / CA / NCI NIH HHS / United States U24 CA076518 / CA / NCI NIH HHS / United States U10 HL069286 / HL / NHLBI NIH HHS / United States U10 HL069330 / HL / NHLBI NIH HHS / United States UL1 TR000114 / TR / NCATS NIH HHS / United States U10 HL069310 / HL / NHLBI NIH HHS / United States U10 HL109137 / HL / NHLBI NIH HHS / United States U10HL069294 / HL / NHLBI NIH HHS / United States K12 HD043488 / HD / NICHD NIH HHS / United States 2K12HD043488 / HD / NICHD NIH HHS / United States |