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IMPACT OF PROCALCITONIN IN THE DIFFERENTIAL DIAGNOSIS OF FEBRILE COMPLICATIONS AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION.
Author(s): ,
Sara Butera
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Torino,Torino,Italy;Department of Oncology, SSD Trapianto Allogenico di Cellule Staminali,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
,
Andrea Evangelista
Affiliations:
Clinical Epidemiology,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
,
Luisa Giaccone
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Torino,Torino,Italy;Department of Oncology, SSD Trapianto Allogenico di Cellule Staminali,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
,
Chiara Dellacasa
Affiliations:
Department of Oncology, SSD Trapianto Allogenico di Cellule Staminali,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
,
Danilo Faraci
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Torino,Torino,Italy;Department of Oncology, SSD Trapianto Allogenico di Cellule Staminali,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
,
Lucia Brunello
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Torino,Torino,Italy;Department of Oncology, SSD Trapianto Allogenico di Cellule Staminali,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
,
Giovannino Ciccone
Affiliations:
Clinical Epidemiology,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
,
Giulio Mengozzi
Affiliations:
Department of Clinical Chemistry, SC Baldi Riberi,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
,
Alessandro Busca
Affiliations:
Department of Oncology, SSD Trapianto Allogenico di Cellule Staminali,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
Benedetto Bruno
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Torino,Torino,Italy;Department of Oncology, SSD Trapianto Allogenico di Cellule Staminali,A.O.U Città della Salute e della Scienza di Torino,Torino,Italy
(Abstract release date: 05/17/18) EHA Library. Bruno B. 06/14/18; 216062; PB2447
Benedetto Bruno
Benedetto Bruno
Contributions
Abstract

Abstract: PB2447

Type: Publication Only

Background

Serum procalcitonin (PCT) has been proposed as a promising diagnostic biomarker for severe bacterial infections in patients with febrile episodes following allogeneic haematopoietic stem cell transplantation (allo-HSCT). A reliable biomarker may be particularly helpful during neutropenic fever.

Aims

The purpose of this study was to determine the potential role of PCT in the differential diagnosis of febrile complications in allo-HSCT recipients.

Methods

Febrile episodes and PCT values were retrospectively reviewed in 553 consecutive allografts performed at our Centre, from January 2007 to December 2016. Biomarkers (PCT and C reactive protein) were assessed in correspondence of the febrile event. Fever work-up also included complete blood counts, haemocultures and chest X-ray. Other imaging studies and/or bronchoalveolar lavage were performed as clinically indicated. A total of 3430 determinations of PCT on 355 patients were analysed. Donors were HLA-identical siblings (no.101); haploidentical (no.58); or unrelated (no.209).

Association between PCT and clinical outcomes were evaluated by generalized linear model with Gamma distribution and link-log.

Results

Frequency of PCT determinations was higher in the first 36 days after transplantation, with a median at +16 days (IQR: 8-36). Overall 210 PCT determinations (6,1%) were performed at the onset and within the first 48 hours of a documented bacterial infection. PCT values were significantly higher in patients with documented gram negative bacteraemia (mean 8.85 ng/ml) compared to patients with no documented infections, with a mean difference of PCT levels of 6.93 ng/ml (95%CI: 1.62, 12.24; p<0.01). PCT showed a promising diagnostic accuracy for Gram negative infections, as compared with inflammatory fever or Gram positive proven bacteraemia. PCT showed a high negative predictive value for bacteraemia regardless of Gram stain, ranging from 97% at cut off value of 2 ng/ml to 96.9% at a cut off value of 0.5 ng/ml. PCT levels superior to 2 ng/ml can be considered specific of bacteraemia with a specificity of 89,5% for gram positive bacteraemia and of 89.7% for gram negative proven infection.

PCT elevations were not significant in patients with documented invasive fungal infections defined by EORTC/MSG criteria (p=0.618), and in patients developing cytokine release syndrome (CRS) after haplo-identical allografts (p=0.207). A mean difference of PCT levels of 6.37 ng/ml was found if anti-thymocyte globulin (ATG) treatment was included as graft-versus-host disease prophylaxis, compared to patients that did not receive ATG. (95%CI: 2.67-10.06; p<0.001).

Multi organ failure was significantly associated with an elevation of PCT values with a mean rise of 3.27 ng/ml in the last 96 hours before death. (95%CI: 1.35, 5.18; p<0.001).

Conclusion

Despite the limitations of the retrospective design of our study and of the low prevalence of proven bacteraemia in correspondence of a PCT determination in our population, PCT may be considered a helpful tool in the differential diagnosis of febrile complications after allo-HSCT. Our findings form the basis for the prospective assessment (in the contest of a clinical trial) of a diagnostic algorithm and scoring system that include PCT determination to evaluate risk of gram negative sepsis and of early mortality in febrile episodes after allografting.

Session topic: 23. Stem cell transplantation - Clinical

Keyword(s): Allogeneic hematopoietic stem cell transplant, Infection, inflammation

Abstract: PB2447

Type: Publication Only

Background

Serum procalcitonin (PCT) has been proposed as a promising diagnostic biomarker for severe bacterial infections in patients with febrile episodes following allogeneic haematopoietic stem cell transplantation (allo-HSCT). A reliable biomarker may be particularly helpful during neutropenic fever.

Aims

The purpose of this study was to determine the potential role of PCT in the differential diagnosis of febrile complications in allo-HSCT recipients.

Methods

Febrile episodes and PCT values were retrospectively reviewed in 553 consecutive allografts performed at our Centre, from January 2007 to December 2016. Biomarkers (PCT and C reactive protein) were assessed in correspondence of the febrile event. Fever work-up also included complete blood counts, haemocultures and chest X-ray. Other imaging studies and/or bronchoalveolar lavage were performed as clinically indicated. A total of 3430 determinations of PCT on 355 patients were analysed. Donors were HLA-identical siblings (no.101); haploidentical (no.58); or unrelated (no.209).

Association between PCT and clinical outcomes were evaluated by generalized linear model with Gamma distribution and link-log.

Results

Frequency of PCT determinations was higher in the first 36 days after transplantation, with a median at +16 days (IQR: 8-36). Overall 210 PCT determinations (6,1%) were performed at the onset and within the first 48 hours of a documented bacterial infection. PCT values were significantly higher in patients with documented gram negative bacteraemia (mean 8.85 ng/ml) compared to patients with no documented infections, with a mean difference of PCT levels of 6.93 ng/ml (95%CI: 1.62, 12.24; p<0.01). PCT showed a promising diagnostic accuracy for Gram negative infections, as compared with inflammatory fever or Gram positive proven bacteraemia. PCT showed a high negative predictive value for bacteraemia regardless of Gram stain, ranging from 97% at cut off value of 2 ng/ml to 96.9% at a cut off value of 0.5 ng/ml. PCT levels superior to 2 ng/ml can be considered specific of bacteraemia with a specificity of 89,5% for gram positive bacteraemia and of 89.7% for gram negative proven infection.

PCT elevations were not significant in patients with documented invasive fungal infections defined by EORTC/MSG criteria (p=0.618), and in patients developing cytokine release syndrome (CRS) after haplo-identical allografts (p=0.207). A mean difference of PCT levels of 6.37 ng/ml was found if anti-thymocyte globulin (ATG) treatment was included as graft-versus-host disease prophylaxis, compared to patients that did not receive ATG. (95%CI: 2.67-10.06; p<0.001).

Multi organ failure was significantly associated with an elevation of PCT values with a mean rise of 3.27 ng/ml in the last 96 hours before death. (95%CI: 1.35, 5.18; p<0.001).

Conclusion

Despite the limitations of the retrospective design of our study and of the low prevalence of proven bacteraemia in correspondence of a PCT determination in our population, PCT may be considered a helpful tool in the differential diagnosis of febrile complications after allo-HSCT. Our findings form the basis for the prospective assessment (in the contest of a clinical trial) of a diagnostic algorithm and scoring system that include PCT determination to evaluate risk of gram negative sepsis and of early mortality in febrile episodes after allografting.

Session topic: 23. Stem cell transplantation - Clinical

Keyword(s): Allogeneic hematopoietic stem cell transplant, Infection, inflammation

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