Longitudinal trajectory patterns of plasma albumin and C-reactive protein levels around diagnosis, relapse, bacteraemia, and death of acute myeloid leukaemia patients

Abstract

Background: No study has evaluated C-reactive protein (CRP) and plasma albumin (PA) levels longitudinally in patients with acute myeloid leukaemia (AML).

Methods: We studied defined events in 818 adult patients with AML in relation to 60,209 CRP and PA measures. We investigated correlations between CRP and PA levels and daily CRP and PA levels in relation to AML diagnosis, AML relapse, or bacteraemia (all ±30 days), and death (─30-0 days).

Results: On the AML diagnosis date (D0), CRP levels increased with higher WHO performance score (PS), e.g. patients with PS 3/4 had 68.1 mg/L higher CRP compared to patients with PS 0, adjusted for relevant covariates. On D0, the PA level declined with increasing PS, e.g. PS 3/4 had 7.54 g/L lower adjusted PA compared to PS 0. CRP and PA levels were inversely correlated for the PA interval 25-55 g/L (R = - 0.51, p < 10-5), but not for ≤24 g/L (R = 0.01, p = 0.57). CRP increases and PA decreases were seen prior to bacteraemia and death, whereas no changes occurred up to AML diagnosis or relapse. CRP increases and PA decreases were also found frequently in individuals, unrelated to a pre-specified event.

Conclusions: PA decrease is an important biomarker for imminent bacteraemia in adult patients with AML.

Keywords: Acute myeloid leukaemia; C-reactive protein; Infection; Inflammation; Plasma albumin.

Fig. 1

Smoothed scatterplot of C-reactive protein and plasma albumin levels. A smoothed scatter plot of C-reactive protein levels (mg/L) in relation to plasma albumin levels (ranging from 11 to 55 g/L, but 11–15 g/L merged with 16 g/L and 51–55 g/L merged with 50 g/L), based on 818 patients with 60,209 specimens in which both CRP and PA were measured. The smoothed colour displays the density of overplotted points (red - > orange - > dark blue - > light blue represent decreasing density). The medians and 95% ranges of values are shown for each value of PA. 602 (1%) points from areas of lowest regional densities are plotted as small points

Fig. 2

Trajectories of C-reactive protein and plasma albumin levels for three patients. Trajectories of levels of C-reactive protein (CRP) in left column and plasma albumin (PA) in right column for three individual patients (designated patient 101, 127, and 170, using encrypted identification numbers). Date of diagnosis of acute myeloid leukaemia (AML) is designated day 0 (D0) on the x-axis (with a solid vertical blue line) and all other days on the x-axis are depicted in relation to D0. The right-most solid vertical black line shows day of death. In between D0 and date of death, solid vertical green lines show day of diagnosis of a bacteraemic episode and the dashed blue line shows day of relapse of AML. All trajectories exclude specimens retrieved > 365 days before D0. For PA, the horizontal line of 35 g/L shows the threshold between normoalbuminemia (≥35 g/L) and hypoalbuminemia (< 35 g/L)

Fig. 3

Daily mean levels of C-reactive protein and plasma albumin, aggregated data. Daily mean levels (95% confidence intervals) of C-reactive protein (CRP) in left column and plasma albumin (PA) in right column, in relation to an event (vertical solid line). Events are, from top to bottom: diagnosis of acute myeloid leukaemia (AML), relapse of AML, first bacteraemic episode, and death. Time spans covers from 30 days before to 30 days after the event, except for death that shows 30 days before death. Events occurring earlier than 30 days in relation to another event were excluded