N-terminal pro-brain natriuretic peptide is a prognostic marker for response to intensive chemotherapy, early death, and overall survival in acute myeloid leukemia

Abstract

Patient-related factors are of prognostic importance in acute myeloid leukemia (AML). Likewise, cardiac disorders may limit the tolerance of intensive therapy. Little is known about the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP). We analyzed NT-proBNP levels at diagnosis in 312 AML patients (median age: 61 years; range 17-89 years) treated with 3 + 7-based induction-chemotherapy and consolidation with up to four cycles of intermediate or high-dose ARA-C. NT-proBNP levels were elevated in 199 patients (63.8%), normal (0-125 pg/ml) in 113 (36.2%), and highly elevated (>2000 pg/ml) in 20 patients (6.4%). Median NT-proBNP levels differed significantly among patients with complete remission (153.3 pg/ml), no remission (225.9 pg/ml), or early death (735.5 pg/ml) (p = .002). In multivariate analysis, NT-proBNP, age, and the 2009 European LeukemiaNet (ELN-2009) classification were independent predictors of outcome after induction chemotherapy. Overall survival (OS) differed significantly between patients with normal, moderately elevated, and highly elevated NT-proBNP (p < .001). These differences were observed in all patients and in patients <60 years but not in those ≥60 years. In multivariate analysis, NT-proBNP, age, and ELN-2009 remained independent prognostic variables for OS (p < .01). Together, NT-proBNP is an independent prognostic factor indicating the risk of induction failure, early death, and reduced OS in patients with AML.

FIGURE 1

Survival in AML patients according to NT‐proBNP levels. Overall survival (OS) in the total cohort differed significantly among patients with normal NT‐proBNP (<125 pg/ml), those with moderately elevated (125–200 pg/ml), and those with highly elevated levels of NT‐proBNP (>2000 pg/ml) (p < .001 by log rank test) (A). Similar differences were observed in patients aged <60 years (p = .012) (B) but not in patients aged ≥60 years (p = .209) (C). The relapse‐free survival (RFS) did not differ significantly according to NT‐proBNP in all patients (p = .261) (D). In the cohort aged <60 years, a significant difference in RFS between patients with moderately (125–200 pg/ml) and highly (>2000) elevated NT‐proBNP (p = .035) (E) was seen, and this difference was not seen in those aged ≥60 years (p = .924) (F)