Infection complications in febrile chimeric antigen receptor (CAR)‐T recipients during the peri‐CAR‐T cell treatment period examined using metagenomic next‐generation sequencing (mNGS)

Nie, Jiali; Yang, Li; Huang, Liang; Gao, Lili; Young, Ken H.; Grange, Jehane Michael Le; Yang, Xiaokui; Wei, Jia; Xiao, Min; Zhou, Jianfeng

doi:10.1002/cac2.12260

Cited by 16 publications

(13 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…mNGS is a microbiologic diagnostic tool that detects all nucleic acids of microorganisms whose sequencing data are included in the database library, thus allowing for an unbiased approach to identify pathogens ( Simner et al., 2018 ). Fast reporting, high accuracy, and the ability to detect multiple pathogens by one test make mNGS a promising microbial detection technology ( Wilson et al., 2019 ), especially in complex miscellaneous infectious diseases among immunosuppressed patients ( Peng et al., 2021 ; Nie et al., 2022 ). Its diagnostic performance has been highlighted in a variety of infectious diseases, such as pneumonia ( Xie et al., 2019 ), blood stream infections ( Jing et al., 2021 ), and central nervous system infections ( Ramachandran and Wilson, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Metagenomic next-generation sequencing for identifying pathogens in patients with rheumatic diseases and diffuse pulmonary lesions: A retrospective diagnostic study

Jiang

Yang

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

ObjectiveLung involvement is a major cause of morbidity and mortality in patients with rheumatic diseases. This study aimed to assess the application value of metagenomic next-generation sequencing (mNGS) for identifying pathogens in patients with rheumatic diseases and diffuse pulmonary lesions.MethodsThis retrospective study included patients who were diagnosed with rheumatic diseases and presenting diffuse pulmonary lesions on chest radiography in Xiangya Hospital from July 2018 to May 2022. Clinical characteristics were summarized, including demographics, symptoms, comorbidities, radiological and laboratory findings, and clinical outcomes. Pulmonary infection features of these patients were analyzed. Furthermore, diagnostic performance of mNGS and conventional methods (including smear microscopy, culture, polymerase chain reaction assay, and serum immunological test) in identifying pulmonary infections and causative pathogens were compared.ResultsA total of 98 patients were included, with a median age of 58.0 years old and a female proportion of 59.2%. Of these patients, 71.4% showed the evidence of pulmonary infections. Combining the results of mNGS and conventional methods, 129 infection events were detected, including 45 bacterial, 40 fungal and 44 viral infection events. Pulmonary mixed infections were observed in 38.8% of patients. The detection rates of mNGS for any pathogen (71.4% vs 40.8%, P < 0.001) and mixed pathogens (40.8% vs 12.2%, P < 0.001) were higher than that of conventional methods. Moreover, mNGS had a significantly higher sensitivity (97.1% vs. 57.1%, P < 0.001) than conventional methods in identifying pulmonary infections, while its specificity (92.9% vs. 96.4%, P = 0.553) were comparable to conventional methods. Antimicrobial and antirheumatic treatments were markedly modified based on mNGS results in patients with rheumatic diseases and diffuse pulmonary lesions.ConclusionsFor patients diagnosed with rheumatic diseases and presenting diffuse pulmonary lesions, mNGS is a powerful complement to conventional methods in pathogen identification due to its high efficiency and broad spectrum. Early application of mNGS can provide guidance for precision treatment, and may reduce mortality and avoid antibiotic abuse.

show abstract

Section: Introductionmentioning

confidence: 99%

Metagenomic next-generation sequencing for identifying pathogens in patients with rheumatic diseases and diffuse pulmonary lesions: A retrospective diagnostic study

Jiang

Yang

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…These children have a significantly higher risk of infection due to secondary humoral immunodeficiency. A recent retrospective study ( 27 ) revealed that the rate of febrile infection in patients during peri-CAR T-cell treatment using NGS detection was as high as 77.45%, of which viral infection was the most common. In this study, three patients who received CAR T-cell treatment had hypogammaglobulinemia for up to approximately half a year, two patients had respiratory tract infections, and one experienced an intestinal infection during the study period.…”

Section: Discussionmentioning

confidence: 99%

Use of blinatumomab and CAR T-cell therapy in children with relapsed/refractory leukemia: A case series study

et al. 2023

View full text Add to dashboard Cite

BackgroundThe 5-year event-free survival rate for childhood acute lymphoblastic leukemia (ALL) has increased to more than 85%. However, the 5-year overall survival rate in children with relapsed/refractory ALL did not exceed 50%. In the past decade, immunotherapies (such as blinatumomab and chimeric antigen receptor T-cell therapy) were approved for relapsed/refractory B-ALL, transforming the treatment environment for children with relapsed/refractory ALL.ObjectiveThis study aimed to explore how immunotherapy can be incorporated into salvage regimens for pediatric patients with relapsed/refractory ALL by retrospectively analyzing the diagnosis and treatment process of seven children with relapsed/refractory leukemia and observing the side effects of the two strategies and long-term survival.MethodsThe clinical features and treatment responses of patients aged <14 years with relapsed/refractory leukemia who received immunotherapy (including Chimeric Antigen Receptor T cell treatment and blinatumomab) at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between February 2014 and April 2022 were retrospectively analyzed.ResultsSeven children underwent immunotherapy. Five patients received immunotherapy and sequential allogeneic hematopoietic stem cell transplantation (HSCT), whereas the other two received only immunotherapy. Five patients achieved complete remission (71.4%). None of the patients had severe cytokine release syndrome. However, one developed grade 3 immune effector cell-associated neurotoxicity syndrome with prior leukoencephalopathy. The median follow-up period was 541 days (range, 186–3,180 days). No deaths were related to treatment. Three patients relapsed, two had CD19-negative recurrences, and the third showed CD19 antigen reduction. One patient died after disease progression, whereas the other died of HSCT-related complications. One patient abandoned the treatment after relapse and was lost to follow-up.ConclusionBlinatumomab and CAR T-cell therapy showed excellent remission rates and manageable toxicity in pediatric patients with relapsed/refractory leukemia. However, the duration of the remission was limited. Therefore, further prospective randomized clinical studies should be conducted to improve the long-term efficacy of immunotherapy.

show abstract

“…CAR-T recipients are highly susceptible to viral infection because of CAR-T cell-mediated immune system dysregulation (29). Viral infections have been be the most common cause of infection in febrile CAR-T recipients in some studies (30). The transfusion targeting B-cell lineages holds the potential to cause long-standing hypogammaglobulinemia, the most common late event potentially lasting for 6 months or longer after transfusion (31).…”

Section: Discussionmentioning

confidence: 99%

CD19/CD22 dual-targeting Chimeric antigen receptor T cell therapy bridging to allogeneic hematopoietic stem cell transplantation for B-cell acute lymphoblastic leukemia delays platelet recovery and increases risks of cytomegalovirus and Epstein-Barr Virus viremia after transplantation

Shijia

Jianrong

et al. 2023

Preprint

View full text Add to dashboard Cite

Integration of chimeric antigen receptor T (CAR-T) cell therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an emerging technology for B-cell acute lymphoblastic leukemia (B-ALL) treatment with unknown impact on HSCT-related complications. We performed a retrospective cohort study of patients receiving CD19/CD22 dual-targeting or CD19 single-targeting CAR-T therapy before HSCT (CD19/CD22 dual-targeting CAR-T group and CD19 single targeting CAR-T group, respectively), and patients did not receive CAR-T therapy before transplantation (non-CAR-T group). Cumulative incidence of platelet engraftment on day 28 was lower in the CD19/CD22 dual-targeting CAR-T group compared to other groups (p=0.028) and it was proved to be an independent risk factor for delayed platelet recovery on day 28 (OR: 2.65; p=0.001). The CD19/CD22 dual-targeting CAR-T bridging to HSCT independently increases risk of early CMV-viremia (HR, 2.96; p=0.001). Both CAR-T groups had higher incidence of 100-day Epstein-Barr virus (EBV)-viremia, compared with the non-CAR-T group (p=0.043 and p=0.001, respectively). Patients receiving CAR-T cell therapy had a higher risk for early EBV-viremia (HR, 6.77; p=0.030). Relapse and survival did not differ between the 3 groups (p>0.05). Integrating CD19/CD22 dual-targeting CAR-T therapy and HSCT delays platelet engraftment and increases the risks of early CMV- and EBV-viremia.

show abstract

Infection complications in febrile chimeric antigen receptor (CAR)‐T recipients during the peri‐CAR‐T cell treatment period examined using metagenomic next‐generation sequencing (mNGS)

Cited by 16 publications

References 11 publications

Metagenomic next-generation sequencing for identifying pathogens in patients with rheumatic diseases and diffuse pulmonary lesions: A retrospective diagnostic study

Metagenomic next-generation sequencing for identifying pathogens in patients with rheumatic diseases and diffuse pulmonary lesions: A retrospective diagnostic study

Use of blinatumomab and CAR T-cell therapy in children with relapsed/refractory leukemia: A case series study

CD19/CD22 dual-targeting Chimeric antigen receptor T cell therapy bridging to allogeneic hematopoietic stem cell transplantation for B-cell acute lymphoblastic leukemia delays platelet recovery and increases risks of cytomegalovirus and Epstein-Barr Virus viremia after transplantation

Contact Info

Product

Resources

About