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DIAGNOSTIC VALUE OF SERUM STREM-1, PROCALCITONIN AND CRP IN PATIENTS WITH FEBRILE NEUTROPENIA
Author(s): ,
Christian Michel
Affiliations:
Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University,Mainz,Germany
,
Daniel Teschner
Affiliations:
Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University,Mainz,Germany
,
Pamela Stein
Affiliations:
Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University,Mainz,Germany
,
Matthias Theobald
Affiliations:
Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University,Mainz,Germany
,
Eva Wagner
Affiliations:
Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University,Mainz,Germany
Markus Radsak
Affiliations:
Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University,Mainz,Germany
(Abstract release date: 05/19/16) EHA Library. Michel C. 06/09/16; 135055; PB2155
Dr. Christian Michel
Dr. Christian Michel
Contributions
Abstract
Abstract: PB2155

Type: Publication Only

Background
The triggering receptor expressed on myeloid cells (TREM)-1 is a transmembrane glycoprotein predominantly expressed on neutrophils and monocytes/macrophages and an important regulator of inflammatory responses. Under inflammatory conditions, TREM-1 is released in a soluble form (sTREM-1) which is of diagnostic value in patients with pneumonia or sepsis in the absence of neutropenia. Severe sepsis in patients with autologous stem cell transplantation is the most abundant cause of death in the first 30 days after transplantation. Early diagnosis of sepsis and adjustment of medical treatment might improve outcome of these patients. Up to date, the potential and diagnostic value of sTREM-1 to predict sepsis and outcome in neutropenic patients undergoing stem cell transplantation has not been explored.

Aims
The aim of our work is to elucidate the diagnostic value of soluble TREM-1 and the correlation with procalcitonin and CRP in patients with febrile neutropenia.

Methods
Blood serum was obtained from 12 male and 5 female inpatients (n=17; median age 62 –IQR 58 to 63y) with a hematological malignancy (8 multiple myeloma, 9 lymphoma) undergoing high dose chemotherapy, followed by autologous stem cell transplantation and presenting for the first time with fever (axillary temp. >38.3°) and neutropenia (PMN <500/μl). sTREM-1 was measured with our self made sTREM-1 ELISA. Procalcitonin and CRP were measured by immunoassays under routine laboratory conditions.All human studies were performed in accordance with the declaration of Helsinki and were approved by the Landesaerztekammer Rhineland-Palatine Ethics Committee according to the institutional guidelines.

Results
At the first episode of febrile neutropenia, the patients had increased levels of CRP of 91 (IQR 42.5 to 161.5) mg/l and PCT of 0.29 (IQR 0.16 to 1.5) ng/ml. Despite severe neutropenia (leukocyte count median 30 (IQR 20 to 60) /nl, median sTREM-1 levels were increased with 33.7 (IQR 14.7 to 98.5) pg/ml. In 12 of 17 patients a bacterial blood infection was documented by positive blood cultures. Patients undergoing a bacterial sepsis showed significantly upregulated levels of sTREM-1 in serum (p=0.001). Additionally elevated sTREM-1 levels significantly correlated with elevated PCT level (r²=0.30; P=0.02). No significant correlation was found between sTREM-1 and CRP (r²=0.04; p= 0.42) or CRP and PCT (r²=0.18; p=0.08).The response to initial empiric antibiotic treatment as well as the subsequent development of serious complications were independent of sTREM-1 levels during first episode of fever. All patients survived 30 days after autologous stem cell transplantation.

Conclusion
We detect elevated levels of sTREM-1 in patients with febrile neutropenia after high dose chemotherapy and autologous stem cell transplantation in the absence of measurable amount of neutrophils and monocytes. Increased level of sTREM-1 significantly correlates with PCT and sepsis. Our results suggest that sTREM-1 might be a useful marker for the early detection of sepsis also in neutropenic patients. However, it is currently unclear whether the malignant hematological disease itself, chemotherapy or autologous stem cell transplantation have an influence on the serum level of sTREM-1. Therefore further prospective studies are on the way to evaluate of sTREM-1 as a clinically relevant or alternative sepsis disease marker in neutropenic patients compared to other well-known markers like PCT or IL-6.

Session topic: E-poster

Keyword(s): Fever, Neutropenia, Sepsis, Stem cell transplant
Abstract: PB2155

Type: Publication Only

Background
The triggering receptor expressed on myeloid cells (TREM)-1 is a transmembrane glycoprotein predominantly expressed on neutrophils and monocytes/macrophages and an important regulator of inflammatory responses. Under inflammatory conditions, TREM-1 is released in a soluble form (sTREM-1) which is of diagnostic value in patients with pneumonia or sepsis in the absence of neutropenia. Severe sepsis in patients with autologous stem cell transplantation is the most abundant cause of death in the first 30 days after transplantation. Early diagnosis of sepsis and adjustment of medical treatment might improve outcome of these patients. Up to date, the potential and diagnostic value of sTREM-1 to predict sepsis and outcome in neutropenic patients undergoing stem cell transplantation has not been explored.

Aims
The aim of our work is to elucidate the diagnostic value of soluble TREM-1 and the correlation with procalcitonin and CRP in patients with febrile neutropenia.

Methods
Blood serum was obtained from 12 male and 5 female inpatients (n=17; median age 62 –IQR 58 to 63y) with a hematological malignancy (8 multiple myeloma, 9 lymphoma) undergoing high dose chemotherapy, followed by autologous stem cell transplantation and presenting for the first time with fever (axillary temp. >38.3°) and neutropenia (PMN <500/μl). sTREM-1 was measured with our self made sTREM-1 ELISA. Procalcitonin and CRP were measured by immunoassays under routine laboratory conditions.All human studies were performed in accordance with the declaration of Helsinki and were approved by the Landesaerztekammer Rhineland-Palatine Ethics Committee according to the institutional guidelines.

Results
At the first episode of febrile neutropenia, the patients had increased levels of CRP of 91 (IQR 42.5 to 161.5) mg/l and PCT of 0.29 (IQR 0.16 to 1.5) ng/ml. Despite severe neutropenia (leukocyte count median 30 (IQR 20 to 60) /nl, median sTREM-1 levels were increased with 33.7 (IQR 14.7 to 98.5) pg/ml. In 12 of 17 patients a bacterial blood infection was documented by positive blood cultures. Patients undergoing a bacterial sepsis showed significantly upregulated levels of sTREM-1 in serum (p=0.001). Additionally elevated sTREM-1 levels significantly correlated with elevated PCT level (r²=0.30; P=0.02). No significant correlation was found between sTREM-1 and CRP (r²=0.04; p= 0.42) or CRP and PCT (r²=0.18; p=0.08).The response to initial empiric antibiotic treatment as well as the subsequent development of serious complications were independent of sTREM-1 levels during first episode of fever. All patients survived 30 days after autologous stem cell transplantation.

Conclusion
We detect elevated levels of sTREM-1 in patients with febrile neutropenia after high dose chemotherapy and autologous stem cell transplantation in the absence of measurable amount of neutrophils and monocytes. Increased level of sTREM-1 significantly correlates with PCT and sepsis. Our results suggest that sTREM-1 might be a useful marker for the early detection of sepsis also in neutropenic patients. However, it is currently unclear whether the malignant hematological disease itself, chemotherapy or autologous stem cell transplantation have an influence on the serum level of sTREM-1. Therefore further prospective studies are on the way to evaluate of sTREM-1 as a clinically relevant or alternative sepsis disease marker in neutropenic patients compared to other well-known markers like PCT or IL-6.

Session topic: E-poster

Keyword(s): Fever, Neutropenia, Sepsis, Stem cell transplant

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