A lesson from fatal invasive fungal infections after CAR-T cell therapy: a case report and literature review
Creators: name: Zhengfeng, Hou
name: Danchen, Meng
name: Min, Ruan
name: Xinglin, Liang
name: Jing, Ni
name: Jifei, Dai
name: Zhonghui, Wu
name: Ruixiang, Xia
name: Jian, Ge
name: Zhangbiao, Long
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Biotechnology
subject: Ecology
subject: Science Policy
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology
subject: Computational Biology

description: CD19 chimeric antigen receptor T (CAR-T) cell therapy represents an effective approach to treating patients with relapsed or refractory B-cell hematologic malignancies. Nevertheless, owing to the immunosuppressive effects of this regimen, patients undergoing CD19 CAR-T cell therapy may face an elevated risk of invasive fungal infections, which involve fungi penetrating the host’s tissues or bloodstream, leading to life-threating infectious diseases. Herein, we present the case of a 17-year-old male diagnosed with acute lymphoblastic leukemia, who subsequently experienced a fatal invasive fungal infection following administration of CAR-T cell therapy. Furthermore, we delve into the identification of risk factors, implementation of preventive measures and exploration of therapeutic interventions for invasive fungal infections after CAR-T cell therapy. A 17-year-old male was diagnosed with acute lymphoblastic leukemia and experienced disease relapse after undergoing multiple chemotherapy treatments. Subsequently, he participated in a clinical trial of CAR-T cell therapy at our institution. Due to a possible lung fungal infection, he was given oral antifungal medicine. Throughout the treatment period, he developed recurrent fever. After receiving immunosuppressive agents, he developed gangrene at the sinuses and was diagnosed with invasive fungal sinusitis. Although antifungal medication was adjusted, it failed to fully eradicate the infection, leading to the patient’s recurrent shocks associated with the fungal infection. These findings underscore the importance for physicians to be vigilant regarding potential fungal infections when administering CAR-T cell therapy, particularly in patients with preexisting fungal infections prior to treatment. Likewise, caution should be exercised in the use of immunosuppressive agents, given their potential to increase the risk of fungal infections, among other complications. Early and timely surgical intervention in the presence of invasive fungal infections may be more effective than monotherapy in some patients with invasive fungal infections. Patients undergoing CD19 chimeric antigen receptor T (CAR-T) cell therapy are at heightened risk of invasive fungal infections due to the immunosuppressive effects of the therapy, especially those with preexisting conditions and prior extensive treatments. A 17-year-old male with acute lymphoblastic leukemia developed fatal invasive fungal sinusitis and pneumonitis following CAR-T cell therapy, despite antifungal prophylaxis. The use of tocilizumab and steroids to manage CAR-T cell therapy side effects may increase the risk of fungal infections, necessitating caution in their use. Evaluate patients for pre-existing fungal infections and consider more aggressive antifungal prophylaxis, particularly for those with prior infections or those receiving extensive immunosuppressive treatments. The patient’s infection progressed despite prophylactic voriconazole and subsequent caspofungin treatment, indicating a need for more effective prophylactic strategies in high-risk patients. In cases of unexplained fever following CAR-T cell therapy, particularly in patients at high risk for fungal infections, the possibility of a fungal infection should not be entirely excluded, even if Galactomannan tests, 1,3-β-D Glucan Tests and fungal cultures are negative. Use potent antifungal agents such as amphotericin B when standard prophylaxis fails. Consider early surgical intervention for invasive fungal infections, as this might improve outcomes. After CAR-T cell therapy, some patients are at high risk for invasive fungal infections. Timely identification of these individuals and the implementation of appropriate measures are crucial.