REVIEW ARTICLE Efficacy and Safety of Recombinant Thrombomodulin for the Prophylaxis of Veno-Occlusive Complication in Allogeneiccit Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Background: Hepatic veno-occlusive disease (VOD), also termed as sinusoidal obstruction syndrome (SOS), is a lethal complication after hematopoietic stem cell transplantation (HSCT). Various factors put patients undergoing allogeneic HSCT at an increased risk for VOD. Thrombomodulin (TM) is an important factor which has a wide range of effects, including anticoagulant, anti-inflammatory, angiogenic, and protective effect, on endothelial cells. It plays a role in preventing excessive coagulation and thrombosis by binding with thrombin and inhibiting the coagulation cascade. There are a limited number of options for the prevention of this fatal complication. Recombinant thrombomodulin (rTM), an endothelial anticoagulant co-factor, as prophylactic therapy might be able to prevent veno-occlusive complications after stem cell transplantation. Methods: A literature search was performed on PubMed, Embase, and Web of Science. We used the following Mesh terms and Emtree terms, “Hepatic Veno-Occlusive Diseases” OR “Sinusoidal Obstruction” OR “Stem Cell Transplantations” AND “Thrombomodulin” from the inception of data up to April 1, 2021. The PICO (Patient/Population, Intervention, Comparison and Outcomes) framework was used for the literature search. Results: For the VOD incidence after HSCTstem cell transplantation, the result was in favor of rTM with a risk ratio (RR) of 0.53 (I² ¼ 0%, 95% confidence interval [CI] ¼ 0.32e0.89). The incidence of transplant-associated thrombotic microangiopathy (TA-TMA) after HSCT was reduced in rTM group. The RR for incidence of TA-TMA was 0.48 (I² ¼ 62%, 95% CI ¼ 0.20e1.17) favoring rTM. The RR for incidence of graft-versus-host disease (GvHD) was also lower in rTM group, 0.48 (I² ¼ 64%, 95% CI ¼ 0.32e0.72). Conclusion: In our meta-analysis, we evaluate the efficacy and safety of rTM in the prevention of SOS after HSCT. According to our results, rTM use led to a significant reduction in SOS episodes, TA-TMA, and GvHD after HSCT.