Understanding how invasive aspergillosis (IA) affects mortality among patients with hematologic malignancies could lead to more accurate sample size estimations in clinical mycology trials, according to researchers at The University of Texas MD Anderson Cancer Center, in Houston.
They reported results of a study in a poster (P1711) at IDWeek 2025, in Atlanta.
“It’s not always clear what the exact cause of death is in patients diagnosed with invasive aspergillosis,” said study co-author Ariel Szvalb, MD, an associate professor at the cancer center. “The disease, by itself, can be lethal, what we call attributable mortality [AM]. There is also a significant amount of contributable mortality [CM], where not only the disease but other associated conditions cause the patient to succumb.
“We think this is relevant because aspergillosis mortality is elevated, and in many trials for anti-leukemic drugs, this has to be taken into account because this infection is a factor that can significantly contribute to the patient’s demise,” Dr. Szvalb told Infectious Disease Special Edition.
Mortality in IA
Dr. Szvalb and colleagues retrospectively reviewed the records of 76 consecutive patients with hematologic malignancies with proven or probable culture-positive IA (based on Mycoses Study Group Education and Research Consortium/European Organisation for Research and Treatment of Cancer criteria) from 2015 to 2021.
Patients had a median age of 60 years. Lymphoma and multiple myeloma were the most common malignancies, at 40 cases (53%) in the sample group; the remaining patients had active leukemia. Twenty-nine patients (38%) had a prior stem cell transplant, and 10 (13%) had graft-versus-host disease. Aspergillus fumigatus was the most common species (47%).
The investigators evaluated mortality rates and causes of death at two-, four-, six-, and 12-week intervals after IA diagnosis. They also performed a multivariate competing risk analysis to identify independent risk factors for six-week AM, with other causes of death as the competing event. To increase diagnostic accuracy, they excluded culture-negative, A. galactomannan–positive cases, as other hyalohyphomycetes can produce galactomannan.
Understanding High Mortality
The six- and 12-week mortality rates were 18.7% and 22.7%, respectively, for AM; 42.7% and 49.3%, respectively, for CM; and 45.3% and 53.3%, respectively, for overall mortality (OM). The two-week OM was 27.6%. The only independent risk factor for six-week AM on multivariate analysis was lack of neutrophil recovery (odds ratio, 4.2; P=0.006).
“That’s important,” Dr. Szvalb said, “because this means that if neutrophils don’t recover, the disease never leaves the host and continues to progress.”
Positive cultures suggest that the patients have an elevated fungal burden and likely a more aggressive disease. “Our findings should impact the design of clinical mycology trials where active Aspergillus infection should not be present,” he said, “because if you look at two-week mortality, it’s already very high. This disease can kill very fast, and if not, it can linger for weeks and contribute to the patient’s death.”
Treatment for patients should include anti-mold agents such as voriconazole, posaconazole, and liposomal amphotericin B, he said. “But the main factor in improving the patient’s outcome is neutrophil count recovery,” he said. “The study results also suggest that antifungal failure should be assessed earlier than the traditional four-week mark post-diagnosis.”
Dr. Szvalb reported no relevant financial disclosures.