Von Willebrand Factor and Factor VIII as potential biomarkers of chronic Graft-versus-Host Disease

Autor: Pulanić, Dražen, Grković, Lana, Serventi- Seiwerth, Ranka, Mravak Stipetić, Marinka, Bilić, Ervina, Čeović, Romana, Perić, Zinaida, Rajić, Ljubica, Duraković, Nadira, Matić, Nikolina, Klepac Pulanić, Tajana, Petriček, Igor, Vukić, Tamara, Bilić, Ernest, Dušek, Davorka, Prenc, Ema, Prah, Iva Ozana, Bojanić, Ines, Grce, Magdalena, Zadro, Renata, Batinić, Drago, Vrhovac, Radovan, Pavletic, Steven, Nemet, Damir
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Popis: Introduction: Predictive, diagnostic, and risk stratification biomarkers of chronic Graft- versus-Host disease (cGVHD) are critically needed to improve treatment of this serious late complication of allogeneic hematopoietic stem cell transplantation (HSCT). Since elevated von Willebrand’s factor (VWF) and factor VIII (FVIII) levels have been described as indicators of endothelial dysfunction and inflammation in different settings, the goal of this study was to assess possible role of VWF and FVIII as potential biomarkers of cGVHD. Materials (or patients) and methods: Multidisciplinary cGVHD clinical infrastructure was organized in 2013 at the Division of Hematology, University Hospital Center Zagreb, Croatia, using established cGVHD-related scales and measurements in collaboration with the National Cancer Institute, National Institutes of Health (NIH), USA. An extensive demography, history, physical and laboratory evaluations were obtained in this cross-sectional prospective study using standardized methods, including measurement of VWF:Ag, VWF:RCo, and FVIII. Descriptive statistic and non-parametric analyses were performed, results with p- valueso0.05 were considered as statistically significant, and variables with Spearman rank correlation coefficient 0.5o|r|o0.7 were considered as moderately correlated. Results: Twenty cGVHD patients were assessed (median age 38.5 years, 55% females). Median time from HSCT to study enrollment was 16.4 months. Median time from HSCT to cGVHD diagnosis was 9.5 months, and median time from cGVHD diagnosis to study enrollment was 5.5 months. Majority of patients (90%) were transplanted for hematologic malignancies. Myeloablative conditioning was used in 50%, 11 (55%) received peripheral blood stem cells, and 12 (60%) transplants were from matched related donors. Eight patients had de novo cGVHD, 5 quiescent, 7 progressive, and 16 (80%) classic cGVHD. Ten (50%) patients had moderate and 10 (50%) severe NIH global cGVHD score. Most involved organs were skin, lung, liver, and eyes. At the time of evaluation, clinician’s impression was in 50% that cGVHD was active. Elevated level of FVIII (median 191%, range 52-297%, reference range 50-149%) and VWF:Ag (median 208%, range 108-600%, reference range 50-160%) was found. Median level of VWF:Rco was 138% (range 75- 547%, reference range 50-150%). Patients after unrelated HSCT had higher FVIII, VWF:Ag and VWF:RCo. Shorter time from cGVHD diagnosis to study enrollment was associated with higher VWF:Ag (P¼0.015) and VWF:Rco (P¼0.018). NIH cGVHD liver score (P¼0.013), average NIH score (r¼0.535), AST (r¼0.668), ALT (r¼0.603), beta-2 microglobulin (r¼0.510), triglyceride (r¼0.596) and cGVHD activity by therapeutic intent (P¼0.019) were associated with higher FVIII. NIH cGVHD mouth score (P¼0.016), clinician impression of cGVHD activity (P¼0.023) and AST (r¼0.563) were associated with higher VWF:Ag. Ferritin (r¼0.506) was associated with higher VWF:RCo, while cGVHD activity by therapeutic intent, beta-2 microglobulin, D-dimers, and triglyceride were associated with both higher VWF:Ag and VWFR:Co. Other markers of inflammation (C-reactive protein, fibrinogen, erythrocyte sedimentation rate) did not correlate neither with VWF:Ag, VWF:RCo nor with FVIII. Conclusion: Results of this pilot study suggest that VWF and FVIII could represent interesting candidate biomarkers of cGVHD. However, these need to be further investigated in larger studies. Disclosure of Interest: None declared.
Databáze: OpenAIRE