Infectious complications of car T-cell therapy: A longitudinal risk model.

BACKGROUND: CAR T-cell therapy, where a patient's own T cells are re-engineered to express a receptor to a target of interest, is becoming an increasingly utilized cancer-directed therapy. There are significant toxicities that contribute to a novel state of immunocompromise, leading to new patterns of infectious complications that require further detailed study. METHODS: We created a single-center cohort of adult recipients of CD19-directed CAR T-cell therapy and assessed infectious outcomes, supportive care received, toxicities, and markers of immune function up to 2 years following CAR T-cell therapy. Descriptive statistics were used as appropriate for analysis. We additionally conducted time-to-event analysis assessing time-to-first infection with either log-rank testing or Cox regression with univariate analysis, before including significant predictors into a multivariate Cox model of time to infection. RESULTS: We identified 73 patients who received CD19-directed CAR T-cell therapy who predominantly had diffuse large B-cell lymphoma. Within 30 days of cell infusion, bacterial and Candida infections were the most common, with 64% of infections due to these organisms. Between 30 days and 2 years postinfusion, respiratory viruses and pneumonia were the most frequent infections, with 68% of infections due to these etiologies. Receipt of tocilizumab, development of immune effector cell-associated neurotoxicity syndrome (ICANS), or lower neutrophil count were associated with quicker onset of infection in a multivariate Cox model. CONCLUSIONS: Respiratory viruses remain an important infectious complication of CAR T-cell therapy following the first year. The model may be a useful tool to identify patients at the highest risk of infection.

Phlegmonous gastritis: Evolving from surgical to medical disease.

We present a case of phlegmonous gastritis, which is a rare, life-threatening infection involving transmural inflammation of the stomach of multiple possible etiologies. Historically this disease has required surgical management, including gastrectomy, which is quite morbid. Evolving literature suggests that antimicrobial therapy alone may be adequate treatment for this infection. The diagnosis of phlegmonous gastritis was suggested by radiology but confirmed by endoscopic pathology. This particular case is unique given the patient's age, lack of co-morbidities and being the first description of Helicobacter pylori with phlegmonous gastritis. We report on a specific successful antimicrobial regimen and duration of therapy, which has not been well documented elsewhere in the literature, which may be helpful to clinicians.

Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients.

Hematopoietic stem cell transplant recipients are at increased risk of infection and immune dysregulation due to reception of cytotoxic chemotherapy; development of graft versus host disease, which necessitates treatment with immunosuppressive medications; and placement of invasive catheters. The prevention and management of infections in these vulnerable hosts is of utmost importance and a key "safety net" in stem cell transplantation. In this review, we provide updates on the prevention and management of CMV infection; invasive fungal infections; bacterial infections; Clostridium difficile infection; and EBV, HHV-6, adenovirus and BK infections. We discuss novel drugs, such as letermovir, isavuconazole, meropenem-vaborbactam and bezlotoxumab; weigh the pros and cons of using fluoroquinolone prophylaxis during neutropenia after stem cell transplantation; and provide updates on important viral infections after hematopoietic stem cell transplant (HSCT). Optimizing the prevention and management of infectious diseases by using the best available evidence will contribute to better outcomes for stem cell transplant recipients, and provide the best possible "safety net" for these immunocompromised hosts.