Elevation of cardiac biomarkers after allogeneic transplantation: the impact of hematopoietic stem cell cryopreservation

Vladimíra Lábska, Beáta Mladosievičová, Michaela Martišová, Barbora Žiaková, Eva Bojtárová, Ladislav Sopko, Jozef Lukáš,  Ľubica Harvanová

Abstract:

Hematopoietic stem cell transplantation (HSCT) represents a curative treatment modality for numerous hematologic malignancies. Advances in treatment protocols and supportive care have markedly enhanced post-transplant survival rates. Consequently, the number of long-term survivors has increased. However, HSCT may induce organ and tissue injury of varying severity, ranging from subclinical alterations to severe, potentially fatal complications. The aim of this study was to quantify plasma levels of the cardiac biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive cardiac troponin T (hs-cTnT), and to evaluate cardiovascular (CV) complications in patients undergoing HSCT with and without cryopreservation of stem cells. During the COVID-19 pandemic, the use of cryopreserved allografts increased. Dimethyl sulfoxide (DMSO) is a cryoprotectant added to cell media to prevent ice formation and subsequent cell death during the freezing process of cryopreserved grafts. This study included 106 consecutive hematologic patients who underwent allogeneic HSCT. Serial measurements of plasma NT-proBNP and hs-cTnT concentrations were performed the day before conditioning regimen (baseline), on the day after HSCT (D+1), and subsequently on days D+2, D+7, D+14, and D+30, or at the onset of clinical symptoms. Newly diagnosed cardiac events post-HSCT were evaluated. NT-proBNP concentrations increased in all patients on D+1 after HSCT, reaching their peak at that time. Thereafter, NT-proBNP levels showed a gradual decline, but they did not return to baseline. A statistically significant increase in NT-proBNP values was observed in the group of patients who received cryopreserved grafts compared to those who received non-cryopreserved grafts. Hs-cTnT values during the early post-transplant period were comparable to pre-transplant levels in both groups - in patients who received cryopreserved grafts and also in patients who received non-cryopreserved grafts. After transplantation, we observed persistent hs-cTnT levels above the cut-off value in 28 % of patients. Clinically significant CV complications were identified in 10 (9.4 %) patients. Patients with manifest CV complications had significantly higher concentrations of both cardiomarkers compared with those without CV complications. In conclusion, persistent elevation in cardiac biomarkers may indicate a reduced functional myocardial reserve or diminished cardiac tolerance to cardiac stressors. Potential cardiac toxicity related to DMSO exposure in cryopreserved grafts should be considered in the differential diagnosis of cardiac events following HSCT involving cryopreserved stem cells.