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

Abstract: 

Background:
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.
Material/methods:
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.
Results:
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).
Conclusions:
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.

Tables: 

2016

Poster: 

AttachmentSize
Image icon P0347.png1.57 MB

abstract No: 

#5461

Full conference title: 

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