Plasma Brain Natriuretic Peptide Is Associated with Hepatic Veno-Occlusive Disease and Early Mortality After Allogeneic Hematopoietic Stem Cell Transplantation.

Fluid retention is usually the first sign and characteristic feature of hepatic veno-occlusive disease (VOD), a life-threatening complication after hematopoietic stem cell transplantation (HSCT). Because brain natriuretic peptide (BNP) is a 32-amino-acid neurohormone synthesized in ventricular myocardium and secreted in response to volume expansion, we hypothesized that plasma BNP concentrations indicate onset and/or severity of VOD and serve as a prognostic marker after HSCT.

We performed a retrospective analysis to see if plasma BNP is associated with VOD and early mortality after allogeneic HSCT. This analysis included 33 consecutive adult patients who underwent allogeneic HSCT at our institution between February 2008 and February 2009. Plasma BNP concentrations (normal range < 18.4 pg/mL) were measured once before transplantation for routine workup and weekly after transplantation, using fluorescence enzyme immunoassay. The diagnosis of VOD was based on modified Seattle criteria and the severity of VOD was defined according to the established criteria.

A total of 7 (21.2%) patients died before day 100, and 12 (36.3%) patients developed VOD (mild to moderate in 6 and severe in 6) between 1 and 15 days (median, 9.5 days) after transplantation. Plasma BNP concentrations were similar before and on day 0 between patients with and without VOD, but significantly increased on day 7 and later in those with VOD. Peak plasma BNP concentrations before engraftment in patients with VOD were significantly elevated compared with those without VOD (median values, 1686.9 pg/mL (range, 459.5 – 10390.9 pg/mL) vs. 87.6 pg/mL (14.3 – 378.8 pg/mL); P = 0.01). Comparison across the severity of VOD revealed that peak plasma BNP concentrations before engraftment were significantly higher in patients with severe VOD than in those with mild to moderate VOD (3678.0 pg/mL (2486.2 – 10390.9 pg/mL) vs. 525.1 pg/mL (459.5 – 887.5 pg/mL); P = 0.02). As most patients presented VOD before day 14, we investigated the impact of plasma BNP on early mortality using peak plasma BNP concentrations before day 14. Receiver operating characteristic curve analysis showed a BNP cutoff value of ≥ 380 pg/mL could effectively differentiate nonsurvivors from survivors at day 100, with a sensitivity of 85.7% and a specificity of 84.6%. Actually, survival at day 100 in patients with peak plasma BNP concentrations of ≥ 380 pg/mL was significantly worse than that in patients with peak plasma BNP concentrations of < 380 pg/mL (40.0% vs. 95.7%; P < 0.01). Because plasma BNP concentrations can be increased in various diseases including heart failure and sepsis, we investigated the associations between plasma BNP concentrations and these conditions. There was no significant difference in peak plasma BNP concentrations before engraftment between patients with and without documented infection (P = 0.72). With respect to cardiac function, pretransplant left ventricular ejection fraction (LVEF) showed no correlation with peak plasma BNP concentrations before engraftment (r = -0.09; P = 0.63). In 6 patients whose peak BNP concentrations were ≥ 1000 pg/mL, cardiac performance was normal or slightly reduced (LVEF ≥ 50%) in 4 patients and moderately deteriorated (LVEF 30 - 50%) in 2 patients when they had peak plasma BNP concentrations.

We found plasma BNP concentrations are elevated in patients with VOD and associated with the severity of VOD and mortality at day 100, irrespective of pretransplant cardiac function and coexistence of documented infection. These findings suggest that plasma BNP may represent a prognostic marker of VOD and could offer a valuable tool toward therapeutic interventions.

No relevant conflicts of interest to declare.