Incidence, outcome and risk factors for invasive aspergillosis. A case control study in 663 allogeneic stem cell transplantation patients

Cornelie Visser, Galai Chong, Jurjen Versluis, Jan Cornelissen, Annoek Broers, Bart Rijnders


Allogeneic hematopoietic stem cell transplantation (HSCT) patients are at high risk for invasive
aspergillosis (IA), an invasive mold infection that is associated with significant morbidity and mortality.
We conducted a retrospective study at a tertiary care hematology center to determine the incidence,
outcome and risk factors for IA in allogeneic HSCT patients.
Medical records of all adult patients who underwent their first allogeneic HSCT at the Erasmus
University Medical Center (Rotterdam, the Netherlands) from 2004-2014, were reviewed.
IA episodes that occurred after HSCT were identified and classified according to the EORTC/MSG
criteria. In addition, patients with a pulmonary infiltrate but without the specific EORTC/MSG
radiological criteria that had a positive serum or bronchoalveolar lavage galactomannan ≥0.5 were
defined as non-classifiable IA. The 12-month mortality after HSCT and the IA-related mortality (6-
weeks mortality after IA) diagnosis was determined.
Within the total cohort, a nested-case control study was performed to determine risk factors for IA.
Patients with proven/probable/non-classifiable IA after allogeneic HSCT were selected as cases, and
patients without IA as controls. Possible IA cases were excluded. Cases were matched to controls 1:2
using age at transplant, year of transplant and duration of follow-up as matching variables. Potential
risk factors were assessed during the month before IA diagnosis in cases and in the same one-month
timeframe in the matched controls. Univariate and multivariate analyses were performed.
In total 663 patients underwent an allogeneic HSCT. At 12-months after HSCT, 109 patients (16.4%)
developed IA of which 1.8% proven, 7.4% probable, 3.8% non-classifiable and 3.5% possible IA.
During the entire follow-up period after HSCT, 137 patients (20.7%) developed IA (2.0% proven, 8.7%
probable, 4.8% non-classifiable and 5.1% possible IA). The median time to IA diagnosis was 149 days
(range 9-2093 days). The IA-related mortality was 29%. The overall mortality 12 months after HSCT
was 40% in patients that developed IA and 26% in those without IA (p-value<0.01).
For the nested case-control study, 99 patients with proven/probable/non-classifiable IA could be
matched with 198 controls. The following independent risk factors were found: reactivation of CMV
(OR 5.47; p-value=0.01), leucopenia (OR 5.33; p-value=0.04) and prednisolone per milligram (OR
1.0014; p-value<0.01). Figure 1 shows the OR of the cumulative dose of prednisolone. A better
glomerular filtration rate was found to be protective (OR 0.97; p-value=0.01).
One year after allogeneic HSCT, 13.0% of the patients had developed a proven/probable/nonclassifiable
IA. One year after HSCT, the overall mortality was 14% higher in patients with than without
IA. Independent risk factors for post-transplantation IA were reactivation of CMV, leukopenia and most
importantly, with every milligram increase of prednisolone dose, the risk for IA increased. In contrast, a
better renal function was found to be protective.




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abstract No: 


Full conference title: 

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