Michael A. Smith, Zachary Hutchinson, Elizabeth Colglazier, Claire Parker, Christine S. Higham, Jeffrey R. Fineman, Matt S. Zinter, Christopher C. Dvorak, Hythem M. Nawaytou
University of California, San Francisco.
Transplantation and Cellular Therapy
Transplant Cell Ther 2025;
DOI: 10.1016/j.jtct.2025.11.024
Abstract
Background: Many life-threatening complications of hematopoietic stem cell transplantation (HSCT) develop secondary to endothelial injury and dysfunction, including transplant-associated thrombotic microangiopathy (TA-TMA), sinusoidal obstruction syndrome, idiopathic pneumonia syndrome, and engraftment syndrome. These endotheliopathies are often accompanied by cardiovascular compromise. Echocardiographic abnormalities including pericardial effusions and elevated right ventricular pressure have previously been identified as early indicators of TA-TMA. Additional echo-derived parameters and serologic metrics of ventricular function are yet to be evaluated as predictors of post-HSCT endotheliopathies and mortality among children.
Objective: We sought to assess the utility of early post-HSCT echo and B-type natriuretic peptide (BNP) screening in predicting the development of TA-TMA, additional endotheliopathies, and death.
Study design: A single center, prospective cohort study was performed after the implementation of a uniform screening protocol at our pediatric hospital. Patients who received a HSCT from 10/2021-8/2023 were screened with echocardiography and serum BNP levels pre-HSCT, day +7 and day +30 from transplant. Changes from baseline in echocardiographic metrics of right and left ventricular function, pericardial effusions, and BNP levels were evaluated as predictors of post-HSCT TA-TMA, additional endotheliopathies, and death.
Results: Fifty-two patients underwent a first HSCT during the study period. The 1-year cumulative incidence of TA-TMA was 13.8 ± 9.6%, of any endotheliopathy was 39.2 ± 13.7% and of death was 13.5 ± 9.4%. Several echocardiographic predictors were found to be associated with the later development of TA-TMA, including pericardial effusions (HR 7.59, 95% CI 1.80-32.00, p=0.006) and measures of increased right and left ventricular function, such as a 10% increase in longitudinal tricuspid annular systolic velocity (tricuspid s’, HR 1.61, 95% CI 1.08-2.38, p=0.018), and a 10% increase in mitral s’ (HR 1.70, 95% CI 1.05-2.75, p=0.031) evaluated at day +30. Similarly, several echocardiographic metrics were associated with the later development of any endotheliopathy, including measures of increased ventricular function such as a 10% increase in tricuspid annular plane systolic excursion (HR 1.43, 95% CI 1.08-1.90, p=0.013) and a 10% increase in mitral s’ (HR 1.28, 95% CI 1.05-1.57, p=0.016) at day +30, as well as a BNP increase of 50pg/ml from baseline at day +7 (HR 2.86, 95% CI 1.15-7.08, p=0.024). Mortality was significantly increased for patients with at least a 10% increase in left ventricular ejection fraction at day +7 (p = 0.035) and pericardial effusions (p = 0.002).
Conclusion: Among pediatric HSCT recipients, acute cardiovascular injury associated with HSCT-related endotheliopathy develops at a subclinical level in the early post-transplant period. Subtle increases in right and left ventricular function, increases in BNP level, and pericardial effusions likely reflect an early response to endothelial injury and are associated with the later development of TA-TMA, other endotheliopathies, and death. Screening protocols and prophylactic and therapeutic interventions for pediatric HSCT recipients should consider these novel cardiovascular biomarkers.
Category
Class V. Pulmonary Hypertension Associated with Hematological, Systemic, Metabolic, Nutritional and Other Disorders
Diagnostic Testing for Pulmonary Vascular Disease. Non-invasive Testing
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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