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INVASIVE ASPEGILLOSIS IN PATIENTS WITH ACUTE LEUKEMIAS: PROGNOSTIC VALUE OF LABORATORY BIOMARKERS DEFINING HIGH RISK PATIENTS
Author(s): ,
Ana Vidovic
Affiliations:
Clinical Center of Serbia, Medical Faculty of Belgrade,Clinic of Hematology,Belgrade,Serbia
,
Valentina Arsic Arsenijevic
Affiliations:
Medical Faculty, University of Belgrade,Medical Mycology Reference Laboratory, Institute of Microbiology and Immunology,Belgrade,Serbia
,
Marijana Virijevic
Affiliations:
Clinical Center of Serbia,Clinic of Hematology,Belgrade,Serbia
,
Dragica Tomin
Affiliations:
Clinical Center of Serbia, Medical Faculty of Belgrade,Clinic of Hematology,Belgrade,Serbia
,
Nada Suvajdzic Vukovic
Affiliations:
Clinical Center of Serbia, Medical Faculty of Belgrade,Clinic of Hematology,Belgrade,Serbia
,
Irena Djunic
Affiliations:
Clinical Center of Serbia, Medical Faculty of Belgrade,Clinic of Hematology,Belgrade,Serbia
,
Mirjana Mitrovic
Affiliations:
Clinical Center of Serbia, Medical Faculty of Belgrade,Clinic of Hematology,Belgrade,Serbia
,
Petar Tojic
Affiliations:
University of Belgrade,Medical Faculty,Belgrade,Serbia
,
Darko Marinkovic
Affiliations:
University of Belgrade,Medical Faculty,Belgrade,Serbia
Biljana Mihaljevic
Affiliations:
Clinical Center of Serbia, Medical Faculty of Belgrade,Clinic of Hematology,Belgrade,Serbia
(Abstract release date: 05/19/16) EHA Library. VIDOVIC A. 06/09/16; 132728; E1179
Prof. Ana VIDOVIC
Prof. Ana VIDOVIC
Contributions
Abstract
Abstract: E1179

Type: Eposter Presentation

Background
Invasive fungal diseases, especially invasive aspergillosis (IA) are the major cause of morbidity and mortality in patients with acute leukemias. Detection of early laboratory biomarkers: galactomannan (GM) and anti-Aspergillus antibodies IgM and IgG (Anti-A IgM, IgG) contributes to early recognition, as well as to the monitoring during aspergillosis treatment.

Aims
The aim of study was to evaluate clinical utility and prognostic value of 'non- culture' methods: GM assay and anti-A (IgM and IgG) antibodies for early diagnosis of aspergillosis in patients with acute leukemias.

Methods
The study included 102 patients, 80 pts with AML and 22 pts with ALL (52 male/50 female, median age 51 years, range 19-73 years) hospitalized in the Clinic of Hematology during period of time from January 2012 until December 2015. All pts were treated with intensive chemotherapy according to the regimens recommended for the treatment AML and ALL, consequently developing febrile neutropenia, with median duration of 12 days (7-23days). Serum GM level were measured twice a weekly using the Platelia Aspergillus enzime immunoassay (EIA) kit (Biorad, France), applying the cutoff value of 0,5 as positivity. Anti-A IgM/anti-A IgG were measured using commercial tests (Serion ELISA classis, Virion/Serion, Germany). The concentration of antibodies above 12U/ml was considered as positive finding. In all patients routine radiological (high resolution CT scaning) was performed, as well as the biological monitoring consisted of hematological, biochemical and cytopathological tests. Median time of follow-up was 294 days (range 15-1300 days) and treatment outcome was assesed on the 100. day of follow-up. Statistical analysis was performed using IBM SPSS Statistics version 21.0.

Results
In analyzed group of 102 patients, there were 20 possible, 54 probable and 4 proven cases of IA, while in the last 24 pts were detected only positive GM or anti-A IgM/anti-A IgG. During 100 days of follow-up, 39 patients died while 63 patients had survival longer than 100 days. GM index, as well as the anti-A (IgM and IgG) antibodies, was defined as ratio of  total number of positive findings and total number of performed tests. Predictive value of GM index was maintained after Cox regression adjustment. In multivariate analysis, GM index was  an independent survival predictor (p = 0.012). Anti-A  IgM  and anti –A IgG were  not  statisticaly significant  predictor  of survival (p=0,224 and  p=0,987).

Conclusion
The GM assay is a useful tool for monitoring IA in patients with acute leukemias. Persistent GM positivity is associated with death and treatment failure, whereas a successful outcome is associated with GM negativity. Diagnostic and prognostic value of level of anti-Aspergillus antibodies is not documented and more studies, with more patients, are needed to define better the role of these biomarkers.

Session topic: E-poster

Keyword(s): Acute leukemia, Aspergillus, Prognostic factor
Abstract: E1179

Type: Eposter Presentation

Background
Invasive fungal diseases, especially invasive aspergillosis (IA) are the major cause of morbidity and mortality in patients with acute leukemias. Detection of early laboratory biomarkers: galactomannan (GM) and anti-Aspergillus antibodies IgM and IgG (Anti-A IgM, IgG) contributes to early recognition, as well as to the monitoring during aspergillosis treatment.

Aims
The aim of study was to evaluate clinical utility and prognostic value of 'non- culture' methods: GM assay and anti-A (IgM and IgG) antibodies for early diagnosis of aspergillosis in patients with acute leukemias.

Methods
The study included 102 patients, 80 pts with AML and 22 pts with ALL (52 male/50 female, median age 51 years, range 19-73 years) hospitalized in the Clinic of Hematology during period of time from January 2012 until December 2015. All pts were treated with intensive chemotherapy according to the regimens recommended for the treatment AML and ALL, consequently developing febrile neutropenia, with median duration of 12 days (7-23days). Serum GM level were measured twice a weekly using the Platelia Aspergillus enzime immunoassay (EIA) kit (Biorad, France), applying the cutoff value of 0,5 as positivity. Anti-A IgM/anti-A IgG were measured using commercial tests (Serion ELISA classis, Virion/Serion, Germany). The concentration of antibodies above 12U/ml was considered as positive finding. In all patients routine radiological (high resolution CT scaning) was performed, as well as the biological monitoring consisted of hematological, biochemical and cytopathological tests. Median time of follow-up was 294 days (range 15-1300 days) and treatment outcome was assesed on the 100. day of follow-up. Statistical analysis was performed using IBM SPSS Statistics version 21.0.

Results
In analyzed group of 102 patients, there were 20 possible, 54 probable and 4 proven cases of IA, while in the last 24 pts were detected only positive GM or anti-A IgM/anti-A IgG. During 100 days of follow-up, 39 patients died while 63 patients had survival longer than 100 days. GM index, as well as the anti-A (IgM and IgG) antibodies, was defined as ratio of  total number of positive findings and total number of performed tests. Predictive value of GM index was maintained after Cox regression adjustment. In multivariate analysis, GM index was  an independent survival predictor (p = 0.012). Anti-A  IgM  and anti –A IgG were  not  statisticaly significant  predictor  of survival (p=0,224 and  p=0,987).

Conclusion
The GM assay is a useful tool for monitoring IA in patients with acute leukemias. Persistent GM positivity is associated with death and treatment failure, whereas a successful outcome is associated with GM negativity. Diagnostic and prognostic value of level of anti-Aspergillus antibodies is not documented and more studies, with more patients, are needed to define better the role of these biomarkers.

Session topic: E-poster

Keyword(s): Acute leukemia, Aspergillus, Prognostic factor

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