Plasma presepsin level is an early diagnostic marker of severe febrile neutropenia in hematologic malignancy patients

Abstract

Background: Febrile neutropenia (FN) is a common infectious complication in chemotherapy. The mortality of FN is higher in hematologic malignancy patients, and early diagnostic marker is needed. Presepsin is a prompt and specific marker for bacterial sepsis, but its efficacy in severe febrile neutropenia (FN) is not well confirmed. We tried to clarify whether it is a useful maker for early diagnosis of FN in patients during massive chemotherapy.

Methods: We measured plasma presepsin levels every 2-3 day in FN cases and evaluated its change during the course of massive chemotherapy. The patients had hematologic malignancy or bone marrow failure, and in all cases, neutropenia was severe during the episode. The baseline levels, onset levels, increase rate at FN onset, and onset / baseline ratio were evaluated for their efficacy of early FN diagnosis.

Results: Eleven episodes of bacteremia (six gram negatives and five gram positives) in severe neutropenia were analyzed in detail. While plasma presepsin level was strongly associated to the CRP level (r = 0.61, p < 0.01), it was not associated with the absolute WBC count (r = -0.19, p = 0.19), absolute neutrophil count (r = -0.11, p = 0.41) or absolute monocyte count (r = -0.12, p = 0.40). The average of onset presepsin level was 638 ± 437 pg/mL and the cutoff value (314 pg/mL) has detected FN onset in 9 of 11 cases. The two cases undetected by presepsin were both Bacillus species bacteremia.

Conclusions: Plasma presepsin level is a reliable marker of FN even in massive chemotherapy with very low white blood cell counts. Closer monitoring of this molecule could be a help for early diagnosis in FN. But bacteremia caused by Bacillus species was an exception in our study.

Keywords: Bacteremia; CD14; Chemotherapy; Febrile neutropenia; Presepsin(soluble CD14-ST).

Fig. 1

Plasma presepsin level change over time and comorbidities. Changes in plasma presepsin level over time in lymphoid malignancy cases (a) and myeloid malignancy cases (b) are shown. Horizontal axis shows the day of chemotherapy. The average of plasma presepsin level was lower in myeloid malignancies. Note that most of the presepsin values are above 100 pg/mL, suggesting that it maintains certain levels even in severe neutropenic state

Fig. 2

Plasma presepsin levels and other parameters measured at the same time point. a Plasma presepsin levels white blood cell count. White blood cell count and plasma presepsin levels were plotted. Plasma presepsin levels were not significantly associated to the absolute white blood cell count(r = −0.19, p = 0.19). Plasma presepsin level was not associated with neutrophil count, or monocyte count, either (data not shown). b Plasma presepsin levels and C-reactive protein (CRP) levels. CRP levels and plasma presepsin levels were plotted. Plasma presepsin levels were strongly associated to the CRP levels. (r = 0.61, p < 0.01)

Fig. 3

Plasma presepsin levels in representative cases. a Case 3; 48 year old male with B-ALL, undergoing “JALSG Ph(−) B-ALL 213 consolidation” chemotherapy. He experienced K.pneumoniae bacteremia on day 10. WBC count was 200/mL and plasma presepsin level was already elevated one day prior FN onset. CRP was not elevated at this time. b Case 4; 68 year old female with MDS and Sweet disease, undergoing induction chemotherapy (MEC-GO). Plasma presepsin level was not elevated in spite of marked leukocytosis (day1) or non-infectious fever caused by erythema nodosa (day24). It was elevated at the onset of S.hominis bacteremia (day8), and at K.pneumoniae bacteremia (day15)