Autonomic Nervous System Pretransplant Malfunction Is a Powerful Predictor of Survival After Allogeneic Hematopoietic Cell Transplantation.

Abstract

Autonomic nervous system function indexed by heart rate variability (HRV) has shown prognostic value for mortality in various cardiovascular and noncardiovascular diseases including cancer. The purpose of this study was to evaluate an association between HRV and outcomes of allogeneic hematopoietic cell transplantation (allo-HCT). We prospectively measured HRV as a surrogate pretransplant marker of autonomic nervous system activity in consecutive allo-HCTs with hematological diseases. We analyzed 112 allo-HCTs performed between July 2011 and July 2013 in our center. Univariate analysis showed that increased values of HRV components (low-frequency [LF] and high-frequency [HF] spectral component), SD of normal-to-normal RR interval (SDNN), and squares of the differences between adjacent normal-to-normal RR intervals (r-MSSD) were significantly associated with decreased probability of overall mortality (hazard ratio = 0.3 for LF, P < 0.001; hazard ratio = 0.3 for HF, P = 0.001; hazard ratio = 0.6 for SDNN, P = 0.004; and hazard ratio = 0.5 for r-MSSD, P = 0.014). Among these 4 indicators, the LF-added pretransplantation assessment of mortality, hematopoietic cell transplantation-comorbidity index, and disease risk index models showed the highest values of ΔAkaike information criterion (16.5, 22.2, and 11.4, respectively). When stratified into quartiles of LF groups, 2-year overall survival was 92.9, 84.5, 59.7, and 33.2%, respectively (P < 0.001). LF alone represented a better discriminating variable for the prediction of mortality when compared with pretransplantation assessment of mortality, hematopoietic cell transplantation-comorbidity index, and disease risk index. In addition, from bivariate analyses, decreased LF was an independent and significant factor for higher overall mortality in all models. Indicators reflective of autonomic nervous system function might be a powerful predictor of survival after allo-HCT.