Survey of serum Aspergillus antigen in patients undergoing chemotherapy for acute myeloid leukaemia or allogeneic haematopoietic stem cell transplantation: role in predicting invasive aspergillosis and in modifying the therapeutic strategy

Florence Persat, Van Hung Tran , Sophie Gardes, Jeremy Monfray, Sophie Ducastelle-Lepretre, Damien Dupont, Mohamad Sobh, Fiorenza Baracco, Hélène Labussière, Xavier Thomas, Franck Nicolini, Caroline Lejeune, Marie Balsat, René Ecochard, Mauricette Michallet


Background: Invasive aspergillosis (IA) remainsanimportant cause of mortalityin immunocompromised acute myeloid leukemia (AML) patients receiving induction chemotherapy and in patients undergoing allogeneic hematopoietic stem  cell transplantation (allo-HSCT) for hematological malignancies. In this study,  we evaluated the performance of different factors in predicting the occurrence of IA, including the Aspergillusantigen galactomannan (GM) detection in sera.

Material/methods: We included all AML patients  receiving induction chemotherapy and patientsundergoing allo-HSCT  for any hematological malignancy  at our center between April  2006 and April 2014. Serologic  detection of circulating GM fungal biomarker was  considered  during the 100 days following the first day of induction chemotherapy in AML patients or from the day of allo-HSCT. Only patients with at least three serum GM  results were considered. The GM tests have been performedroutinely using the ELISA kit (Platelia Aspergillusantigen ELISA, Biorad), giving the results in    index. IA cases were  classified as proven or probable according to the EORTC criteria. The  value of the first antigen test, the  delay to positivity, and the slope of the  progression of the index value between  the first two antigens concentrations were considered as predictors of IA. 

Results: A  total of 775 patients were  included:  292 AML and 483 allo-HSCT patients.  During the follow-up, we identified 121 episodes with at least one positive GM test with a   cumulative incidence at day 100 of 13.8%. We also diagnosed 48 IA (2 proven, 46 probable), with a   cumulative incidence at day 100 of 5.5% in total, 7.2% in    AML and 4.3% in    allo-HSCT, respectively. We then classified the GM positive episodes in    82 false-positive (68%) and 39 true-positive episodes (32%) for IA, respectively. A majority of IA events occurred  during the first  30 days of  follow  up,  GM positivity showing a   positive predictive value of 41% versus a negative predictive value of 99%. The three IA predictor factors had similar independent effects and their combinations were performed, allowing establishing an area under ROC of  0.79  (95%  CI:  0.70-0.89). Cut off values of the first positive GM serum  and slope were  equal or higher than 1.04 and 0.04, respectively, and delay to positivity equal or less than 15 days. A prognostic score defining the IA risk probability was defined as the number of predictors present (values from 0   to 3). This score was tested on positive follow-up and a score superior or equal to 2 was indicative of IA in  62% of the cases.

Conclusions: As  IA has a  significant impact on hematology patient’s survival,  this  GM predictive score combining three predictors (value of  the first antigen index, delay of positivity  and slope of the index values) may help clinicians to conclude about starting an early preemptive IA treatment.


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European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 26th (2016)