Early molecular diagnosis of aspergillosis in a patient with acute myeloid leukaemia

Abstract

Diagnosis of invasive fungal infection remains challenging. Here we report a case of early diagnosis of invasive aspergillosis in a neutropenic patient affected by acute myeloid leukaemia, achieved through the detection of Aspergillus fumigatus species-specific ribonucleic acid sequences by a sensitive multiplex real-time polymerase chain reaction-based molecular assay. Thanks to the early diagnosis, targeted therapy was promptly established and the severe fungal infection controlled, allowing the patient to subsequently receive allogeneic hematopoietic stem cell transplantation from a haploidentical donor, her only curative option. Also in this instance, targeted secondary antifungal prophylaxis with voriconazole avoided any other fungal infection afterwards. This report suggests how the implementation of molecular assays in combination with routine diagnostic procedures, can improve microbiological diagnosis in sepsis, particularly in case of fungal infection, difficult to detect with standard microbiological culture methods.

Keywords: allogeneic transplant; aspergillus fumigatus; molecular diagnosis; sepsis; voriconazole..

Figure 1

Temporal sequence of patient’s sepsis, from hospital admission to haploidentical HSCT, with detailed clinical and laboratory steps.HSCT = hematopoietic stem cell transplantation; CT = computerized tomography; BAL = bronchoalveolar lavage; GM = galactomannan.

Figure 2

Chest CT scan of the patient shows a large consolidation area and peripheral ground-glass opacities in left lower lobe. CT = computerized tomography.

Figure 3

Cytology on bronchoalveolar lavage: septate hyphae, suggestive for Aspergillus, and foamy macrophages.

Figure 4

Chest CT scan of the patient, performed 10 days after starting of the targeted antifungal therapy, showed a marked reduction of the lobar pneumonia and particularly of the ground-glass opacities. CT = computerized tomography.

Figure 5

Immune reconstitution after allogeneic HSCT: absolute counts of lymphocyte subpopulations of CD3+, CD4+ and CD8+ T cells, assessed by whole blood immunophenotypic staining with specific monoclonal antibodies (all from Biolegend) and Flow-Count Fluorospheres (Beckman Coulter), acquired using a Gallios cytometer and analyzed with Kaluza software (all from Beckman Coulter). HSCT = hematopoietic stem cell transplantation; GvHD = graft versus host disease.