Disease risk and GVHD biomarkers can stratify patients for risk of relapse and nonrelapse mortality post hematopoietic cell transplant

Abstract

The graft-versus-leukemia (GVL) effect after allogeneic hematopoietic cell transplant (HCT) can prevent relapse but the risk of severe graft-vs-host disease (GVHD) leads to prolonged intensive immunosuppression and possible blunting of the GVL effect. Strategies to reduce immunosuppression in order to prevent relapse have been offset by increases in severe GVHD and non-relapse mortality (NRM). We recently validated the MAGIC algorithm probability (MAP) that predicts the risk for severe GVHD and NRM in asymptomatic patients using serum biomarkers. In this study we tested whether the MAP could identify patients whose risk for relapse is higher than their risk for severe GVHD and NRM. The multicenter study population (n=1604) was divided into two cohorts: historical (2006–2015, n=702) and current (2015–2017, n=902) with similar non-relapse mortality, relapse, and survival. On day 28 post-HCT, patients who had not developed GVHD (75% of the population) and who possessed a low MAP were at much higher risk for relapse (24%) than severe GVHD and NRM (16% and 9%); this difference was even more pronounced in patients with a high disease risk index (relapse 33%, NRM 9%). Such patients are good candidates to test relapse prevention strategies that might enhance GVL.

Early vascular endothelial complications after hematopoietic cell transplantation: Role of the endotheliopathy in biomarkers and target therapies development

“…Identifying different soluble biomarkers has also permitted the design of different panels for diagnosis or prognostic stratification. Paczesny et al developed a model composed by four biomarkers (Il-2, TNFR1, IL-8, and HGF) for the laboratory confirmation of GvHD and its prognostic stratification In the same line, and using proteomics approaches, the Mount Sinai Acute GVHD International Consortium (MAGIC) went a step further and validated an algorithm for the prediction of the risk of severe GvHD, non-relapse mortality (NRM) (141) and longterm outcomes in patients with steroid-refractory GVHD (142). Although the model was composed of two parameters meant as gastrointestinal-damage biomarkers (ST2 and REG3 a), ST2 is also produced by endothelial cells, supporting the need for assessing endothelial biomarkers in other prognostic scores.…”

Association between P2X7 Polymorphisms and Post-Transplant Outcomes in Allogeneic Haematopoietic Stem Cell Transplantation

“…Studies to identify markers of patient outcomes in alloSCT have often focused on the biology of donor cells. Conversely, recipient immunology has been infrequently studied as a determinant of transplant outcome, although more recently, circulating biomarkers linked to recipient tissue damage have been used to prognostically determine survival in aGVHD [29]. Factors such as P2X7 activation might alter the clearance of tissue antigens and limit the speed and activation status of donor T cells.…”

Combined C-Reactive Protein and Novel Inflammatory Parameters as a Predictor in Cancer—What Can We Learn from the Hematological Experience?

“…These studies showed that the initial response reflected in this algorithm after one week of steroid treatment correlated with the treatment response after 28 days as well the one-year nonrelapse mortality and one-year survival. Recently they also showed that the day 28 score in patients without signs of acute GVHD could be used to discriminate between patients with a low risk of later GVHD (9% with later acute GVHD) and a higher risk of later relapse (24% general risk but 33% risk in patients with high risk disease) [ 92 ]. For such patient it will then be reasonable to rapidly decrease the immunosuppressive GVHD prophylaxis and, thereby, increase antileukemic immune reactivity and decrease the risk of later relapse.…”