Abstract
Even with high-dose post-transplant cyclophosphamide (PT-Cy) which was initially introduced for graft-versus-host disease (GvHD) prevention in the setting of HLA-haploidentical transplantation, both acute and chronic GvHDs remain a major clinical challenge. Despite improvements in the understanding of the pathogenesis of both acute and chronic GvHDs, reliable biomarkers that predict their onset have yet to be identified. We recently studied the potential correlation between extracellular vesicles (EVs) and the onset of acute (a)GvHD in transplant recipients from related and unrelated donors. In the present study, we further investigated the role of the expression profile of membrane proteins and their microRNA (miRNA) cargo (miRNA100, miRNA155, and miRNA194) in predicting the onset of aGvHD in haploidentical transplant recipients with PT-Cy. Thirty-two consecutive patients were included. We evaluated the expression profile of EVs, by flow cytometry, and their miRNA cargo, by real-time PCR, at baseline, prior, and at different time points following transplant. Using logistic regression and Cox proportional hazard models, a significant association between expression profiles of antigens such as CD146, CD31, CD140a, CD120a, CD26, CD144, and CD30 on EVs, and their miRNA cargo with the onset of aGvHD was observed. Moreover, we also investigated a potential correlation between EV expression profile and cargo with plasma biomarkers (e.g., ST2, sTNFR1, and REG3a) that had been associated with aGVHD previously. This analysis showed that the combination of CD146, sTNFR1, and miR100 or miR194 strongly correlated with the onset of aGvHD (AUROC >0.975). A large prospective multicenter study is currently in progress to validate our findings.
Highlights
Hematopoietic cell transplantation (HCT) represents a potentially curative strategy for several hematological malignancies
Our findings showed that these changes were detectable several weeks before the onset of acute GvHD (aGvHD) (Figure 2)
CD146 is a marker of activated endothelial cells, expressed by CCR5+ T helper 17 (Th17) cells which expand during gastrointestinal aGVHD [29, 30]
Summary
Hematopoietic cell transplantation (HCT) represents a potentially curative strategy for several hematological malignancies. The use of post-transplant cyclophosphamide (PT-Cy) as graft-vs.-host disease (GvHD) prophylaxis led to a considerable expansion of haploidentical transplants (Haplo-HCT) with remarkable clinical outcomes [1]. Both acute and chronic GvHDs remain life-threatening complications [2, 3]. To predict their onset and develop preemptive interventions, the identification of reliable biomarkers still represents an unmet need. To date, none of these biomarkers have been able to universally predict either risk or severity of developing GvHD
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