Interleukin-6 as Biomarker for Acute GvHD and Survival After Allogeneic Transplant With Post-transplant Cyclophosphamide

• Published in: Frontiers in immunology Vol. 10; p. 2319
• Main Authors: Greco, Raffaella, Lorentino, Francesca, Nitti, Rosamaria, Lupo Stanghellini, Maria Teresa, Giglio, Fabio, Clerici, Daniela, Xue, Elisabetta, Lazzari, Lorenzo, Piemontese, Simona, Mastaglio, Sara, Assanelli, Andrea, Marktel, Sarah, Corti, Consuelo, Bernardi, Massimo, Ciceri, Fabio, Peccatori, Jacopo
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01.10.2019
• Subjects: allogeneic hematopoietic stem cell transplantation; graft-vs.-host disease; Immunology; interleukin-6; overall survival; transplant-related mortality; transplant-related mortality; overall survival; graft-vs.-host disease; interleukin-6; allogeneic hematopoietic stem cell transplantation
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.02319

Although the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) has dramatically improved in the past decade, it is still compromised by transplant-related mortality (TRM), mainly caused by Graft-vs. -Host Disease (GvHD). We conducted a prospective observational study to ascertain the potential of serum interleukin-6 (IL6) levels, measured before conditioning and 7 days after allo-HSCT, in predicting acute GvHD, TRM and survival after allo-HSCT with Post-Transplant Cyclophosphamide (PT-Cy) based GvHD prophylaxis. Between April 2014 and June 2017, we collected samples from 166 consecutive allo-HSCT patients. By ROC analysis, we identified a threshold of 2.5 pg/ml for pre-transplant IL6 and 16.5 pg/ml for post-transplant IL6. Both univariate and multivariate analyses confirmed the ability of high baseline IL6 levels to predict worse OS (HR 4.3; < 0.01) and grade II-IV acute GvHD (HR 1.8; = 0.04), and of high post-transplant IL6 to identify patients with worse OS (HR 3.3; < 0.01) and higher risk of grade II-IV (HR 5; < 0.01) and grade III-IV acute GvHD (HR 10.2; < 0.01). In multivariate analysis, both baseline (HR 6.7; < 0.01) and post-transplant high IL6 levels (HR 3.5; = 0.02) predicted higher TRM. IL6 may contribute to the risk stratification of patients at major risk for aGvHD and TRM, potentially providing a window for additional prophylactic or preemptive strategies to improve the quality of life in the early post-transplant phase and the outcome of allo-HSCT.