Blastemia portrays a poor prognosis in acute leukemia patients with invasive pulmonary aspergillosis

Objectives: Severe and prolonged neutropenia is associated with poor outcomes of invasive pulmonary aspergillosis (IPA) in leukemia patients. Given the high frequency of IPA in patients with relapsed/refractory leukemia, we studied the association of peripheral blood blast burden (blastemia), IPA outcomes, and antifungal immune failure, even without neutropenia. Methods: We retrospectively reviewed adult patients with acute leukemia (AL) or myelodysplastic syndrome and culture-positive proven/probable IPA (2011-2022). Blast and neutropenia indices were calculated and incorporated into multi-variable prognostic models. The impact of blasts on immune cell-mediated fungal clearance was studied in vitro. Results: Among 74 patients, 69% had neutropenia and 57% had blastemia at IPA diagnosis. Blast index >= 90 at IPA diagnosis and >= 3 lines of prior chemotherapies were independent predictors of 42-day mortality and early antifungal treatment failure. Leukemic blasts had minimal immune activity against Aspergillus fumigatus and impaired fungal inhibition by peripheral blood mononuclear cells. Conclusion: Blastemia is common in contemporary leukemia patients with IPA and is a significant risk factor for poor IPA outcomes, possibly due to interference with fungal clearance by immune cells. Therefore, blastemia should be considered as a risk stratification parameter in future mycology trials and as an experimental variable in preclinical IPA models. (c) 2025 Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).