Annalisa Paviglianiti, Clinical Hematology Department, Institut Català d'Oncologia-Hospitalet, Barcelona, Spain, comments on the publication entitled “Prospective external validation of biomarkers to predict acute graft-versus-host disease severity” published in Blood Advances.
Prospective external validation of biomarkers to predict acute graft-versus-host disease severity
Robin M et al.
Blood Adv. 2022 Aug 23;6(16):4763-4772. doi.org/10.1182/bloodadvances.2022007477
Acute graft-versus-host disease (GVHD) is still one of the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. The incidence varies according to graft source, age and gender of the recipient and the donor, type of donor, conditioning regimen and GvHD prophylaxis used. We know that acute GvHD can occur in 30 to 50% of patients according to these factors. We also have enough published data about the association between acute GvHD and graft-versus-hematological disease effect allowing to reduce the relapse incidence. However, biomarkers helping to predict the response and/or the severity of GvHD are still lacking in the clinical practice. Up to 50% of recipients with acute GvHD would experience a steroid-refractory disease, which is associated with high mortality and morbidity. Therefore the use of specific tools and biomarkers able to predict the response to treatment is an important concern in this setting.
The authors reported 204 patients who experienced acute GvHD requiring systemic steroid treatment and included in a prospective non-interventional study. The aim of the study was to test the ability of different panels including 7 biomarkers (Elafin, HGF, IL2RA, IL8, REG3, ST2, and TNFRI), to predict complete response to steroid at day 28 and overall survival (OS) and non-relapse mortality (NRM) at 180 days. Multivariate analysis showed that age more than 50 years, liver involvement at onset of GvHD and grade 3 GvHD were associated with higher risk of no response at day 28. Initial grade 3 and liver involvement were both significantly associated with lower OS and NRM.
After adjustment on clinical variables, biomarkers were associated with OS and NRM and they slightly improved the prediction of both outcomes. The potential benefit of adding biomarkers panel to clinical parameters was also investigated by decision curve analyses. Biomarkers did not add predictive value to clinical parameters in MVA in an adjusted Cox regression model. This finding was confirmed also when comparing the discrimination models (C-index). This is in contrast with the results of the original panel 6 article by Levine et al., where none of the clinical parameters predicted response to treatment. Biomarkers previously published by the Ann Arbor/MAGIC consortium were also reported as objective tools being able to predict outcomes.
This single center prospective study provide insight into the field of acute GvHD, by testing biomarkers at the onset of the disease in a prospective trial. The study have some limitations, mostly the limited number of patients preventing the authors to provide a subgroup analysis. This article points out that biomarkers are complementary tools to clinical parameters that could eventually be used in the future to predict response to first-line therapy and allow for promptly adjustment of treatment to prevent steroid-refractory GVHD mortality.
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