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Background Ruxolitinib (Jakafi), is an oral kinase inhibitor that works by inhibiting the activity of JAK1 and JAK2. JAK 1 and JAK 2 are molecules that play a prominent role in the signaling of cytokines, growth factors and cellular responses relevant to growth, development and immune functions in humans. Jakafi treatment is indicated for polycythemia vera, myelofibrosis, acute graft-versus-host disease, and hypereosinophilic leukemia. 1 Methods Case report and review of literature.Results An 88-year-old male with hypereosinophilic leukemia (treated with Jakafi for 10 years) developed sudden cough, weight loss, hemoptysis, shortness of breath (desaturation to 80%). He had been gardening. CT scan revealed left upper lobe obliteration, nodules with ground-glass opacities ( figures 1 and 2). COVID and TB testing was negative. Bronchoscopy and culture results confirmed invasive Aspergillosis pneumonia and sepsis, specifically arising from an infection by Aspergillus fumigatus. He was prescribed voriconazole for 6 months and made a complete recovery except for lung scarring. Throughout his treatment, care was taken to monitor the levels and dosages of voriconazole, Jakafi, and his prostate medications, all metabolized by the cytochrome P450 enzyme CYP3A4 in the liverConclusions Jakafi has had great success in the treatments of various cancers. 1 Opportunistic infections during treatment is a possible complication.2 Providers and patients should be cognizant of this potentially lethal secondary infection. Preventive measures, such as HEPA filters, masks, and early detection is crucial. Monitoring and adjustment of medication and drug-drug interaction are crucial.References Song J, Song M, PHan V, Weinberg JB, Palmares TM, Song A, Lee S, Mortara L. Ruxolitinib in treatment of refractory hypereosinophilic syndrome. Journal of Clinical Oncology. 35;7_suppl. https://doi.org/10.1200/JCO.2017.35.7_suppl.73Dioverti MV, Abu OM, Tande AJ. Infectious complications in patients on treatment with Ruxolitinib: case report and review of the literature. Infectious Diseases. 2017;50(5):381–387. https://doi.org/10.1080/23744235.2017.1390248Ethics Approval This was a retrospective case report.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journalAbstract 1076 Figure 1Chest X-rayAbstract 1076 Figure 2CT scan chest