Aspergillus RNA In The Blood Of Patients Is A Promising Alternative Biomarker For Invasive Aspergillosis

Ref ID: 18637

Author:

Y. Zhao, PhD – Research Associate1 P. Paderu, MS – Research Associate 1, R. Fox, BS – Assoc Early Clinical Scientist 2, C. Douglas, PhD – Target ID lead 2, R. Railkar, PhD – Associate Director 2, N. Shire, PhD – Director 2, D. Perlin, PhD – Executive

Author address:

1PHRI center, UMDNJ, Newark, NJ, 2Merck & Co., Inc., North Wales, PA.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Invasive Aspergillosis (IA) commonly develops in recipients of allogeneic stem cell transplantation and solid-organ transplantation. Despite recent advances in new antifungal treatments, the mortality rate for IA remains high at 30-50%. A significant challenge in the development of antifungal therapies for IA is the lack of reliable biomarkers to assess early treatment response.
Methods:To assess the kinetics of fungal RNA in the blood following administration of antifungal therapy, serial blood was drawn from 50 patients diagnosed as proven (7) or probable (43) IA according to EORTC/MSG diagnostic criteria, at 8 specified time points including baseline (8804; 24h prior to initiation of antifungal therapy), week 1 assessment 1&2, week 2 assessment 1&2, week 4, 6, and 12. Total nucleic acid was extracted from 2.5 ml blood aliquots in PAXgene® RNA tubes and tested by pan-Aspergillus real-time nucleic acid sequence-based amplification (NASBA) assay. Serum 1,3-β -D-glucan (BG) and galactomannan (GM) were measured by Fungitell and Platelia assays, respectively. Clinical outcome was evaluated at 6 and 12 weeks. Results:Thirty patients had at least one NASBA positive blood. The detection rate was 60% (30/50) for NASBA, compared to 30.6% (15/49) for GM and 75% (36/48) for BG. Of 23 patients classified as clinical failure at week 6, 69.6% (16/23) were NASBA positive, 40.9% (9/22) were GM positive, and 71.4% (15/21) were BG positive. The detection rate for other 24 patients with success outcome (complete or partial response) at week 6 was 58.3% (14/24) for NASBA, 20.8% (5/24) for GM, and 75% (18/24) for BG. A changing profile of blood fungal RNA burden following antifungal therapy was observed, as the most frequent positive NASBA detections were from baseline and week 4 with earlier time to positivity values compared to other time points.
Conclusions:The kinetic profile of NASBA indices reflects the changing pattern of blood fungal burden in patients with IA, and may be correlated with therapeutic response.

Abstract Number: M-1678

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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