title: Relapsed and secondary disease drive the risk profile for invasive aspergillosis prior to stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndrome.
abstract: Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) are at risk for invasive aspergillosis (IA) even prior to the introduction of stem cell transplantation (SCT). In times of increasing triazole resistance and changing use of antifungal prophylaxis, insight into the risk factors for IA is needed to improve strategies for preventing IA in this population. Consecutive patients who received remission-induction therapy for AML or MDS at the Leiden Academic Medical Centre were included. Instead of standard antifungal prophylaxis, an assertive protocol for diagnosis of suspected fungal infection was in place. IA was classified according to the revised European Organization for Research and Treatment of Cancer criteria. Potential predisposing characteristics for IA were compared by uni- and multivariate analyses. In 45 (25%) of 184 included episodes (167 patients), IA was diagnosed prior to SCT. A multivariate Cox regression model demonstrated that relapsed AML (hazard ratio [HR] 2.4; 95% confidence interval [CI], 1.1-5.1; P = 0.02), secondary AML (HR, 5.2; 95% CI, 2.3-11.8; P < 0.001), and prolonged duration of neutropenia (HR, 2.2; 95% CI, 1.2-4.0; P = 0.01) were independently associated with IA. Use of granulocyte-colony-stimulating factor showed a trend toward a protective effect (HR, 0.37; 95% CI, 0.1-31.0; P = 0.06). Relapsed AML, secondary AML, and duration of neutropenia were independent factors for determining the risk for development of IA prior to SCT. The results provide further guidance for antifungal stewardship programs when integrating individual patient tailored decision making in antifungal prophylaxis strategies.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van de Peppel
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter A
authors.initials: PA
authors.lastname: von dem Borne
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands M.G.J.de_Boer@lumc.nl.
authors.forename: Mark G J
authors.initials: MG
authors.lastname: de Boer
mesh_terms: D015331:Cohort Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D055744:Invasive Pulmonary Aspergillosis / Q000453:epidemiology* / Q000517:prevention & control; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000628:therapy; D012008:Recurrence; D012307:Risk Factors; D033581:Stem Cell Transplantation
chemical_list: D007155:Immunologic Factors; D016179:Granulocyte Colony-Stimulating Factor
keywords: AML; MDS; antifungal stewardship; chemoprophylaxis; invasive aspergillosis; resistance; risk factors