Pre-transplant cardiovascular risk and overall survival after allogeneic stem cell transplantation

Background

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for hematologic malignancies but is associated with substantial non-relapse morbidity and mortality. Cardiovascular disease and cardiovascular risk factors impact long-term outcomes in cancer patients, yet their prognostic relevance in allo-SCT patients remain incompletely defined. This study aimed to evaluate the impact of pre-transplant cardiovascular risk factors, cardiac function, and cardiac biomarkers on overall survival after allo-SCT.

Methods

We retrospectively analyzed 349 patients (≥18 years) who underwent allo-SCT between 2011 and 2020 at a single tertiary center. Pre-transplant cardiovascular risk factors included diabetes mellitus, hypertension, chronic kidney disease (CKD) and dyslipidemia. Cardiovascular risk was defined as the presence of at least one of these factors. Baseline assessment of cardiac function comprised transthoracic echocardiography (left ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), electrocardiography (sinus rhythm yes/no), heart rate (category 1: <60/min, n = 24; category 2: 60-79/min, n = 149; category 3: 80-99/min, n = 130; category 4: >99/min, n = 37), and cardiac biomarkers (high-sensitivity troponin, NT-proBNP). Cox proportional hazards regression analyses were performed to screen for variables associated with overall survival. Variables associated with overall survival in univariate Cox regression analyses were entered into multivariable Cox proportional hazards models adjusted for recipient age at transplantation, sex, and underlying hematological disease. Hazard ratios with 95% confidence intervals are reported.

Results

Diabetes and presence of sinus rhythm were associated with OS in univariate analysis but did not retain independent significance after multivariable adjustment. In multivariable Cox regression analyses, we saw that chronic kidney disease was independently associated with inferior overall survival (HR 2.11, 95% CI 1.44-3.09; p < 0.001). Higher heart rate categories were also independently associated with worse survival, with a stepwise increase in risk across categories (category 3: HR 2.21, 95% CI 1.04-4.66; p = 0.038; category 4: HR 3.40, 95% CI 1.51-7.64; p = 0.003). It was also shown that elevated troponin T was independently associated with inferior overall survival (HR 1.98 per log unit, 95% CI 1.19-3.29; p = 0.008), after adjustment for recipient age, sex, and underlying disease group. NT-proBNP was not independently associated with overall survival (HR 1.06 per log unit, p = 0.56) (Table 2).

Summary

Comorbidities prior to transplantation, such as CKD and elevated heart rate, as well as acute myocardial damage - as indicated by troponin T levels - should be taken into account before transplantation and optimized if necessary, as these are factors that may be associated with worse overall survival rates.