Cho Sung-Yeon, Wurster Sebastian, Jiang Ying, Bazinet Alexandre, Hui Yang, Lewis Russel E, Matsuo Takahiro, Albert Nathaniel, Garcia-Manero Guillermo, Kontoyiannis Dimitrios P
Department of Infectious Diseases, University of Texas, MD Anderson Cancer Center, TX, United States; Division of Infectious Diseases, Department of Internal Medicine, Vaccine Bio Research Institute, Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea.
Department of Infectious Diseases, University of Texas, MD Anderson Cancer Center, TX, United States.
J Infect. 2025 Aug;91(2):106535. doi: 10.1016/j.jinf.2025.106535. Epub 2025 Jun 16.
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.
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.
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.
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.
严重且持续时间长的中性粒细胞减少与白血病患者侵袭性肺曲霉病（IPA）的不良预后相关。鉴于复发/难治性白血病患者中IPA的发生率较高，我们研究了外周血原始细胞负荷（白血病原始细胞血症）、IPA预后和抗真菌免疫功能衰竭之间的关联，即使在没有中性粒细胞减少的情况下。
我们回顾性分析了2011年至2022年期间患有急性白血病（AL）或骨髓增生异常综合征且培养阳性确诊/疑似IPA的成年患者。计算原始细胞和中性粒细胞减少指数，并将其纳入多变量预后模型。在体外研究原始细胞对免疫细胞介导的真菌清除的影响。
在74例患者中，69%在IPA诊断时有中性粒细胞减少，57%有白血病原始细胞血症。IPA诊断时原始细胞指数≥90以及既往接受≥3线化疗是42天死亡率和早期抗真菌治疗失败的独立预测因素。白血病原始细胞对烟曲霉的免疫活性极低，且外周血单个核细胞对真菌的抑制作用受损。
白血病原始细胞血症在当代患有IPA的白血病患者中很常见，并且是IPA预后不良的重要危险因素，可能是由于其干扰了免疫细胞对真菌的清除。因此，白血病原始细胞血症应在未来的真菌学试验中被视为风险分层参数，并在临床前IPA模型中作为实验变量。
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