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3573 Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) and Growth Differentiation Factor-15 (GDF-15) Leves Are Significantly Associated with Edothelial Injury Indices in Adult Allogenic Hematopoietic Cell Transplantation Recipients

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster II
Hematology Disease Topics & Pathways:
Research, adult, Clinical Research, Diseases, Study Population, Human
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Eleni Gavriilaki, MD, PhD1, Zoi Bousiou, MD, MSc2*, Ioannis Batsis3*, Anna Vardi4*, Despina Mallouri3*, Evdoxia Koravou5*, Georgia Konstantinidou6*, Nikolaos Spyridis, MD3*, Georgios Karavalakis6*, Vasileios Patriarcheas7*, Marianna Masmanidou6*, Tasoula Touloumenidou8*, Apostolia Papalexandri, MD9*, Christos Poziopoulos, MD10*, Evangelia Yannaki, MD6*, Ioanna Sakellari6*, Marianna Politou11* and Ioannis Papassotiriou, PhD12

12nd Propedeutic Department of Internal Medicine, George Papanicolaou General Hospital, Thessaloniki, Greece
2Hematology Dept.-BMT Unit, George Papanicolaou General Hospital, Thessaloniki, GRC
3Hematology Department – BMT Unit, G Papanikolaou Hospital, Thessaloniki, Greece
4G Papanicolaou Hospital, Thessaloniki, Greece
5Hematology Department & HCT Unit, G. Papanicolaou Hospital, Thessaloniki, GRC
6Hematology Dept. - BMT Unit, George Papanicolaou General Hospital, Thessaloniki, Greece
7Hematology Dept. - BMT Unit, George Papanicolaou General Hospital, THESSALONIKI, Greece
8Hematology Dept. - BMT Unit, Georgios Papanicolaou General Hospital, Thessaloniki, Greece
9George Papanicolaou General Hospital, Thessaloniki, Greece
10Department of Hematology, Metropolitan Hospital, Neo Faliro, Greece
11National and Kapodistrian University of Athens, Medical School, Athens, GRC
12First Department of Pediatrics, National and Kapodistrian University of Athens, School of Medicine, Athens, Attica, Greece

Introduction: Endothelial dysfunction is a common denominator of graft-versus-host disease (GVHD) and transplant-associated thrombotic microangiopathy (TA-TMA). Among endothelial injury indices, the Endothelial Activation and Stress Index (EASIX) has been studied in allogeneic hematopoietic cell transplantation recipients (allo-HCT) recipients, while others including suPAR and GDF-15 have been determined only in other patient populations with hematologic diseases, such as in patients with Multiple Myeloma, AL- amyloidosis and Sickle Cell Disease. We hypothesized that suPAR and GDF-15 would reflect endothelial injury in allo-HCT recipients.

Methods: We enrolled consecutive adult TA-TMA (classified according to current standardized criteria), acute and/or chronic graft-versus-host-disease (GVHD), control allogeneic hematopoietic cell transplantation (alloHCT) recipients and apparently healthy individuals of similar age and gender in a 1:1:1:1 ratio. Plasma was collected and stored immediately at -80oC at the first day of confirmed TA-TMA or GVHD diagnosis and at a similar post-transplant period in control recipients. EASIX [lactate dehydrogenase (U/L) × creatinine (mg/dL)/thrombocytes (10⁹ cells per L)] was calculated at day 0, 30, 100 and at last follow-up. Soluble C5b-9/membrane attack complex, suPAR and GDF-15 levels were measured using immunoenzymatic techniques.

Results: We studied 20 TA-TMA, 20 GVHD, 20 control alloHCT patients, and 20 healthy controls. We found significantly higher suPAR and GDF-15 levels in TA-TMA and GVHD patients compared to alloHCT and healthy controls (p<0.001, Bonferroni’s correction). Then, we further analyzed characteristics of the alloHCT population.

TA-TMA developed at a median of 125 post-transplant day (range 9-2931); whereas the first day of confirmed GVHD diagnosis was at a median of 78 post-transplant day (range 16-145). Both GDF-15 and suPAR concentrations were associated with EASIX at day 100 (r=0.351, p=0.012 and r=0.338, p=0.015, respectively) and last follow-up (r=0.473, p<0.001 and r=0.410, p=0.020, respectively). Among the laboratory values used to calculate EASIX (LDH, creatinine, platelets), suPAR was associated with creatinine and platelets at day 100 and last follow-up; while GDF-15 only with platelets at both time points, suggesting that the association with EASIX is not driven by laboratory values per se. Interestingly, only suPAR and not GDF-15 levels was associated with soluble C5b-9 levels (p=0.013), a marker reflecting high risk in TA-TMA.

Conclusion: Our study shows for the first time that suPAR and GDF-15 reflect endothelial injury in allo-HCT recipients. In accordance with other patient populations, suPAR emerges as a marker of renal dysfunction, characterizing high-risk in endothelial injury syndromes and in particular, TA-TMA. However, prior to their clinical usefulness, these biomarkers must undergo through rigorous validation in multiple cohorts.

Disclosures: Gavriilaki: Alexion, AstraZeneca, Omeros, Sanofi, Sobi: Honoraria; Pfizer and Jazz Pharmaceuticals: Research Funding.

*signifies non-member of ASH