Decoding Graft-versus-Host Disease: Can We Predict Patient Outcomes?
"New research sheds light on biomarkers that could predict survival rates in acute graft-versus-host disease (GVHD) patients after reduced-intensity conditioning."
For over a decade, the study and analysis of biomarkers to diagnose and predict disease outcomes have seen a surge. These biomarkers, which can be any clinical parameter or protein linked to an individual's health status, are assessed using both new and established platforms to visualize protein and peptide expression in tissues and body fluids. Much of the research focuses on discovering new protein or peptide biomarkers, clusters, or patterns in body fluids like blood and urine.
Allogeneic hematopoietic stem-cell transplantation (HSCT) serves as a curative treatment for patients battling hematological malignancies or hematopoietic failure syndromes. However, its use is often hindered by severe complications, notably acute and chronic graft-versus-host disease (GVHD). Consequently, numerous research teams have been dedicated to identifying biomarkers capable of predicting the onset of acute GVHD, offering prognostic insights for detecting steroid resistance, and ultimately, forecasting mortality post-GVHD. A notable advancement in this area is the use of urine proteomics, employing capillary electrophoresis coupled online with mass spectrometry, which currently stands as the sole model for predicting acute GVHD development.
The Endothelial Activation and Stress Index (EASIX), which combines routinely monitored clinical biomarkers post-HSCT, offers a practical approach. Based on lactate dehydrogenase, creatinine, and platelet count, EASIX predicts mortality in acute GVHD patients after reduced-intensity conditioning. Its straightforward formula—lactate dehydrogenase (U/L) × creatinine (mg/dL)/thrombocytes (10⁹ cells per L)—makes identifying patients unlikely to respond to steroid therapy remarkably simple.
EASIX-GVHD: A Promising Tool with Limitations
The ability to predict mortality in acute GVHD patients has garnered significant attention in recent years. Protein biomarkers, assessed at the onset of acute GVHD using ELISA, have been extensively published. While initial studies suggested the necessity of measuring six biomarkers for accurate prediction, advancements have refined this to two key markers: suppression of tumorigenicity 2 (ST2) and serum or plasma Reg3alpha. While these biomarkers effectively predict mortality post-acute GVHD onset and overall HSCT outcomes, the costs associated with the platform used to acquire this information can be substantial. In contrast, EASIX-GVHD, as described by Thomas Luft and colleagues, utilizes routinely measured parameters in allogeneic HSCT patients.
- Variations in Conditioning Intensities: Reduced-intensity conditioning varies considerably, which can lead to substantial variations in platelet counts, potentially affecting the accuracy of survival predictions.
- Limited Scope of Parameters: The hazard ratio of overall survival is only 1.2 in both univariable and multivariable analyses, suggesting that the parameters building up the EASIX-GVHD score cannot account for all of the pathophysiological changes occurring during acute GVHD.
Future Directions: Refining Prediction Models for GVHD Outcomes
Luft and colleagues' work adds to the existing scientific literature on biomarker development for prediction of death after GVHD with a simple tool that can be easily applied to any patient cohort.
Expansion of the present cohorts might lead to improved insights into the importance of conditioning regimens, and whether EASIX-GVHD retains its predictive value in patients receiving different reduced-intensity conditioning protocols remains to be shown in future studies.
Further studies with larger cohorts, especially comparing the biomarkers described for prediction of acute GVHD and outcome with the biomarkers for prediction of outcome after acute GVHD, preferably done in the centres that first published the analyses of the biomarkers, would be interesting and are well overdue. EASIX-GVHD could be included in these analyses and the predictive value of the markers could be analysed in a large multicentre trial.