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SYNOPSISInfections with the fungus Talaromyces (formerly Penicillium)marneffei are rare in patients who do not have AIDS. Wereport disseminated T. marneffei infection in 4 hematologypatients without AIDS who received targeted therapy withmonoclonal antibodies against CD20 or kinase inhibitorsduring the past 2 years. Clinicians should be aware of thisemerging complication, especially in patients from diseaseendemicregions.Talaromyces (formerly Penicillium) marneffei is apathogenic, thermal dimorphic fungus that causes systemicmycosis in Southeast Asia. T. marneffei infection ischaracterized by fungal invasion of multiple organ systems,especially blood, bone marrow, skin, lungs, and reticuloendothelialtissues, and is highly fatal, especially whendiagnosis and treatment are delayed (1,2). This disease isfound predominantly in AIDS patients and occasionallythose with cell-mediated immunodeficiencies involvingthe interleukin-12/interferon-γ (IFN-γ) signaling pathway,such as congenital STAT1 mutations or acquired autoantibodiesagainst IFN-γ (1,3–6). The infection has rarely beenreported among hematology patients, including those fromdisease-endemic regions (7,8).At Queen Mary Hospital in Hong Kong, a 1,600-beduniversity teaching hospital that has a hematopoietic stemcell transplantation service, where a wide range of invasivefungal infections have been observed (9,10), only 3cases of T. marneffei infection were encountered in >2,000hematology patients in the past 20 years, despite the longstandingavailability of mycologic culture and serologictesting (7,8,11,12). In contrast, the infection was commonlyreported among AIDS patients (13).In the past 2 years, we have been alerted by 4 unprecedentedcases of disseminated T. marneffei infection amongnon-AIDS hematology patients given targeted therapies,including monoclonal antibodies (mAbs) against CD20and kinase inhibitors, which are being increasingly usedin recent years. We report details for these 4 hematologycase-patients. The study was approved by the institutionalreview board of The University of Hong Kong/HospitalAuthority Hong Kong West Cluster in Hong Kong.Case-Patient 1Patient 1 was a 56-year-old Filipino man with Waldenströmmacroglobulinemia, idiopathic thrombocytopenicpurpura, and primary biliary cirrhosis. He had fever,night sweating, productive cough, and left facial pain for1 week and bloody diarrhea for 2 days. He had previouslyreceived fludarabine, dexamethasone, and rituximab (mAbagainst CD20, 18 months earlier) for treatment of Waldenströmmacroglobulinemia (Table 1). The idiopathicthrombocytopenic purpura was controlled with intravenousimmunoglobulin and maintenance prednisolone andmycophenolate sodium. A chest radiograph showed a smallcavitary lesion in the right lower lobe. His symptoms andsigns did not resolve after he received empirical intravenousimipenem/cilastatin and metronidazole (Table 2).A colonoscopy showed multiple shallow ulcers at theterminal ileum (Figure 1). Histologic analysis of an ulcerbiopsy specimen showed slough of an acutely inflamed ulcerbut no microorganisms. However, histologic analysisof a specimen from a nasopharyngeal biopsy performedfor persistent left facial pain showed abundant yeast cellsengulfed by foamy macrophages (Figure 2). Culture ofterminal ileal ulcer biopsy specimens, stool samples, andnasopharyngeal biopsy specimens yielded T. marneffei.A contrast-enhanced cranial computed tomography (CT)scan showed 2 lesions (3–4-mm) with rim enhancementand perifocal edema at the right occipital and left parietooccipitallobes. A thoracic CT scan showed 2 cavitary lesions(4–8 mm) in the right upper and lower lobes.Immunologic testing showed that the patient was negativefor HIV and autoantibodies against IFN-γ. His CD3+and CD8+ counts were within references ranges, but he hadmild CD4+ lymphopenia (Table 2). His fever and symptomsresolved with after 2 weeks of treatment with intravenousliposomal amphotericin B, followed by oral voriconazole.Reassessment colonoscopy (at 2 months) and CT scan (at 6months) showed complete resolution of all lesions.Case-Patient 2Patient 2 was a 44-year-old Chinese man who had feverfor 2 days. He had previously received chemotherapy andmAbs against CD20 (rituximab, 14 months earlier; obinutuzumab,concomitant) for refractory chronic lymphocyticleukemia (CLL) involving bone marrow (Table 1). He wasempirically given intravenous piperacillin/tazobactam andanidulafungin (Table 2). Histologic analysis of a trephinebiopsy specimen showed persistent CLL with plasmacyticdifferentiation, and Grocott staining showed yeasts withcentral septa in small clusters. Culture of peripheral bloodand bone marrow aspirate yielded T. marneffei. A changein antifungal treatment to intravenous amphotericin B ledto defervescence and clearance of fungemia. He was givenoral itraconazole as maintenance therapy. He remainedwell until 2 months later when he was hospitalized fordeteriorating CLL complicated by neutropenic fever withmultiorgan failure caused by other opportunistic infections(Table 1). He died 5 months after the episode of disseminatedT. marneffei infection.Case-Patient 3Patient 3 was a 63-year-old Chinese man with myelofibrosisand well-controlled diabetes mellitus. He had intermittentfever, right cervical lymphadenopathy, and productivecough for 4 months. He was given ruxolitinib (kinase1102 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015