Endothelial Activation and Stress Index-Measured Pretransplantation Predicts Transplantation-Related Mortality in Patients with Thalassemia Major Undergoing Transplantation with Thiotepa, Treosulfan, and Fludarabine Conditioning

• Published in: Transplantation and cellular therapy 2022-07, Vol.28 (7), p.356.e1-356.e6
• Main Authors: Kulkarni, Uday P., Pai, Aswin Anand, Kavitha, ML, Selvarajan, Sushil, Lionel, Sharon, Devasia, Anup J., Korula, Anu, Fouzia, NA, Sindhuvi, Eunice, Abraham, Aby, Srivastava, Alok, Mathews, Vikram, George, Biju, Balasubramanian, Poonkuzhali
• Format: Article
• Language: English
• Subjects: Biomarkers; Endothelial Activation and Stress Index; Hemoglobinopathies
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2022.05.001

•Biomarkers to predict transplantation-related mortality (TRM) in patients with class III thalassemia undergoing hematopoietic stem cell transplantation (HCT) are needed.•A novel biomarker, the Endothelial Activation and Stress Index (EASIX), appears to be predictive of TRM in these patients.•Prospective validation of this biomarker is needed. The use of thiotepa-treosulfan-fludarabine conditioning regimen and peripheral blood stem cell grafts is associated with improved outcomes of hematopoietic stem cell transplantation (HCT) in patients with high-risk thalassemia major. However, there remains a need to identify predictors of poor outcomes in this cohort to further optimize outcomes. The Endothelial Activation and Stress Index (EASIX) is a biomarker shown to predict survival in various settings, including graft-versus-host disease, veno-occlusive disease, and nonrelapse mortality following allogeneic HCT. In this retrospective analysis, we evaluated the role of EASIX-PreTx (measured before conditioning therapy) as a biomarker in predicting day +100 transplantation-related mortality (TRM+100) in 281 patients with thalassemia major who underwent HCT with a uniform conditioning regimen using thiotepa-treosulfan-fludarabine at our center between January 2012 and December 2019. The median patient age was 9 years (range, 1 to 25 years), and 109 (38.8%) were females. According to the Pesaro classification (with Vellore modification), 3 patients (1.1%) were class I, 34 (12.1%) were class II, 134 (47.7%) were class III low risk, and 110 (39.1%) were class III high risk. Stem cell donors were matched sibling (n = 218; 77.6%), matched related nonsibling (n = 23; 8.2%), or matched unrelated (n = 40; 14.2%). Five patients (1.8%) received a bone marrow graft, and the others received a peripheral blood stem cell graft. Thirty-eight patients (13.5%) had TRM+100. EASIX-PreTx was available for 184 patients (65.5%). The median EASIX-PreTx was significantly higher in patients with TRM+100 compared with those without TRM+100 (1.09 versus .75; P = .008). An EASIX-PreTx cutoff of .85 had 70.4% sensitivity and 62% specificity for predicting TRM+100. The TRM+100 for patients with EASIX-PreTx >.85 was significantly higher than those with EASIX