Infection Complications after Lymphodepletion and Dosing of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia or B Cell Non-Hodgkin Lymphoma

被引:34
作者
Korell, Felix [1 ]
Schubert, Maria-Luisa [1 ]
Sauer, Tim [1 ]
Schmitt, Anita [1 ]
Derigs, Patrick [1 ]
Weber, Tim Frederik [2 ]
Schnitzler, Paul [3 ]
Mueller-Tidow, Carsten [1 ]
Dreger, Peter [1 ]
Schmitt, Michael [1 ]
机构
[1] Univ Hosp Heidelberg, Dept Internal Med Hematol Oncol & Rheumatol 5, D-69120 Heidelberg, Germany
[2] Univ Hosp Heidelberg, Dept Diagnost & Intervent Radiol, D-69120 Heidelberg, Germany
[3] Univ Hosp Heidelberg, Dept Virol, D-69120 Heidelberg, Germany
关键词
CAR-T cell; infection; lymphodepletion; cytokine release syndrome; AXICABTAGENE CILOLEUCEL;
D O I
10.3390/cancers13071684
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary Chimeric antigen receptor T (CAR-T) cells have become clinical practice for the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma. The aim of this retrospective study was to assess infection complications after lymphodepletion and CAR-T cell therapy. Infections were commonly detected, but manageable in most cases. Fast and appropriate identification as well as treatment were critical, especially in this very vulnerable patient group. Effective strategies to prevent infections as well as adequate medical management also include standardized prophylaxis and additional supportive therapy. Chimeric antigen receptor T (CAR-T) cell therapy has proven to be very effective in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). However, infections-related either due to lymphodepletion or the CAR-T cell therapy itself-can result in severe and potentially life-threatening complications, while side effects such as cytokine release syndrome (CRS) might complicate differential diagnosis. Sixty-seven dosings of CAR-T cells in sixty adult patients with NHL (85%) and ALL (15%) receiving CAR-T cell therapy were assessed for infectious complications. Almost two-thirds of patients (61%) developed fever following lymphodepletion and CAR-T cell dosing. Microbiological or radiological findings were observed in 25% of all cases (bacterial 12%, viral 5%, fungal 8%). Inpatient infections were associated with more lines of therapy and more severe CRS. However, overall serious complications were rare after CAR-T therapy, with one patient dying of infection. Pathogen detection after inpatient stay was infrequent and mostly occurred in the first 90 days after dosing. Infections in CAR-T cell treated patents are common. Fast and suitable identification and treatment are crucial in these heavily pretreated and immunocompromised patients. In most cases infectious complications are manageable. Nonetheless, standardized anti-infective prophylaxis and supportive therapy are mandatory to reduce morbidity and mortality in CAR-T cell therapy.
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