PB1267 - Endothelial damage biomarkers panel to predict response to extracorporeal photopheresis in steroid refractory acute GVHD patients

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Julia Martinez-Sanchez, MS

PhD student
Josep Carreras Leukaemia Research Institute, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain

Co-Author(s)

MP

Marta Palomo

PhD
Josep Carreras Leukaemia Research Institute, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
OP

Olaf Penack

Medical Doctor
Hematology, Oncology and Tumorimmunology Department, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Berlin, Berlin, Germany
Ana Belén Moreno-Castaño, MD

Medical Doctor
Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
ST

Sergi Torramade-Moix

PhD
Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
AR

Alex Ramos

Predoctoral Student
Josep Carreras Leukaemia Research Institute (Campus Clinic). Barcelona
Barcelona, Catalonia, Spain
HV

Helena Ventosa-Capell

MD, PhD Student
Hematopathology, Department of Pathology, Centre de Diagnostic Biomedic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
Barcelona, Catalonia, Spain
MR

Montserrat Rovira

Medical Doctor
Hematology Department, Bone Marrow Transplantation Unit, Institut Clínic de Malalties Hemato-Oncològiques (ICMHO), Hospital Clínic, Barcelona, Spain.
Barcelona, Catalonia, Spain
GE

Gines Escolar

MD PhD Senior Consultant
Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
EC

Enric Carreras

Medical Doctor
Josep Carreras Leukaemia Research Institute, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
JC

Joan Cid

Medical Doctor
Apheresis & Cellular Therapy Unit, Department of Hemotherapy and Hemostasis, ICMHO, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Maribel Diaz-Ricart, PhD

Senior Researcher
Hospital Clinic, IDIBAPS, University of Barcelona, Spain
Barcelona, Catalonia, Spain

Background: Extracorporeal photopheresis (ECP) is an effective and safe procedure in treating patients with symptomatic graft-versus-host disease (GVHD). ECP is used as a second line treatment for those patients with acute GVHD (aGVHD) who are steroid-refractory (SR-aGVHD). Clinical and experimental evidence demonstrates that endothelial damage is involved in aGVHD. Therefore, sustained endothelial dysfunction may be a pathophysiological substrate for SR-aGVHD.

Aims: To measure circulating endothelial damage biomarkers to: i) analyze the degree of endothelial damage in SR-aGVHD patients before initiating ECP; ii) investigate the effect of ECP on the endothelial activation state, and iii) explore differences depending on the response to ECP.

Methods: SR-aGVHD patients treated with ECP (n=35) were classified into good (GR) and bad (BR) responders depending on their clinical improvement after ECP. Plasma samples were collected at initiation (PRE) and at the end (POST) of ECP treatment. We analyzed endothelial activation biomarkers, such as soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), von Willebrand Factor (VWF), thrombomodulin (TM), soluble TNF receptor 1 (sTNFR1), and angiopoietin 2 (ANG2); GVHD markers, such as suppression of tumorigenicity 2 (ST2), regenerating islet-derived 3-alpha (REG3alpha), and T-cell immunoglobulinmucin-3 (TIM3); soluble C5b9 (sC5b9) for complement activation; and circulating dsDNA for neutrophil extracellular traps (NETs). Results were compared in each group and between both groups.

Results: Decreased levels of sTNFR1, TIM3, sC5b9, sVCAM-1, TM, ST2 and ANG2 were observed in PRE samples of GR vs. BR (Table 1). Levels of these markers did not change substantially in the GR POST samples, whereas most of them kept increasing in the BR group. Association of those biomarkers with AUC>0.60 (ROC curves) resulted in PPV of 94.44% and NPV of 54.55% to negatively respond to EPC (p < 0.009).

Conclusion(s): We propose a panel of endothelial damage biomarkers in patients with SR-aGVHD that could predict the clinical response to ECP.