Whether early or preemptive corticosteroids and immunomodulators should continue to be used to mitigate CAR T-cell therapy-related toxic effects, when such a strategy is associated with an increased ...risk of infections and diminished SARS-CoV-2 vaccine responses, remains a timely question and probably will involve a balancing act.1 To that end, Topp and colleagues2 and Caimi and colleagues3 provided a set of results showing the potential of preemptive corticosteroids and tocilizumab, respectively, to mitigate the risks of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).2,3 A subgroup analysis by Topp and colleagues from the pivotal ZUMA-1 trial evaluated the incidence and severity of CRS and ICANS (primary endpoints in cohort 4) with early administration of corticosteroids and tocilizumab. The association between cumulative corticosteroid dose and duration and increased risk of infections has been shown in several studies examining CD19 and B-cell maturation antigen-targeted CAR T-cells.7 This is an important safety consideration as infections are among the most common causes of mortality in CAR T-cell therapy recipients, second only to CRS and ICANS.8 In the era of an ongoing pandemic and continuous emergence of variants of concern, clinical practice and research related to CAR T-cell therapy needs redirection. Importantly, evolving data related to SARS-CoV-2 vaccine responses in patients with cancer suggest that humoral immune responses might be substantially blunted in CAR T-cell therapy recipients, with corticosteroids being identified as the primary driver of diminished vaccine responses.7 Although there might not be an immediate solution to the problem, exploratory studies showing the feasibility of CAR.λ and CAR.κ T cells hold potential for a minimal effect on humoral immunity.
More than 2 million people were rendered homeless.2 The economic loss is estimated to be more than USD $30 billion, but the affected regions are facing health-care issues that have not been accounted ...for.3 Among the many infectious diseases spreading rapidly in flood-affected areas, dengue infection has seen an unprecedented increase. According to the National Institute of Health, Pakistan, almost 26 000 cases of dengue were confirmed from Jan 1 to Sep 27, with 74% (>19 000) of these cases being reported in September alone. ...a population-based cohort study showed that a previous dengue virus infection was associated with a 3-fold increase in the risk of leukaemia compared with no dengue infection.10 The damage caused by climate change is not only catastrophic but also well beyond just brick and mortar.
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, ...dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut–lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a “leaky gut”. The intestinal permeability then allows access to bacterial products and toxins into the circulatory system and further exacerbates the systemic inflammatory response. In this review, we discuss the available data related to the role of the gut microbiome in the development and progression of COVID-19. We provide mechanistic insights into early data with a focus on immunological crosstalk and the microbiome’s potential as a biomarker and therapeutic target.
Evolving data suggest that SARS‐CoV‐2 vaccine responses are blunted in allogeneic hematopoeitic cell transplant (HCT) recipients. Responses to the vaccine in chimeric antigen receptor T‐cell (CAR‐T) ...therapy are unknown and are likely to be even more diminished. We manually searched vital databases and identified 5 studies that have so far reported COVID‐19 vaccine response in a total of 70 CAR‐T recipients. The cumulative humoral response rate across all 5 studies was 31%. However, the results are not generalizable due to non‐standardized units of humoral response measurement and a lack of external validation. Heterogeneity existed in studies regarding the timing of vaccination post‐CAR‐T, intervals between the vaccine doses, platforms of response assessment, vaccine platforms, and pre‐vaccine immune status. CAR‐T‐related factors that independently impact vaccine response to prevent COVID‐19 have further been reviewed. We conclude that the results must be interpreted with caution given the limitations of small sample sizes, differences in immunoassays, lack of standard definitions and clinical correlates of SARS‐CoV‐2 immune response, and lack of cellular responses. Until large‐scale, homogenous prospective data become available, these preliminary observations will help transplant and infectious disease clinicians with their decision‐making while providing care to this profoundly immunosuppressed cohort of patients.
Summary
Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)‐matched ...allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA‐haploidentical HCT recipients who receive post‐transplant cyclophosphamide (PTCy)‐based graft‐versus‐host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin‐based GVHD prophylaxis (SibCNI, N = 1605) or PTCy (SibCy, N = 403), and related haploidentical transplants receiving PTCy (HaploCy, N = 757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment‐related mortality hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13–4⋅07; P = 0⋅002 and inferior 2‐year overall survival (HR 1⋅65, 99% CI 1⋅11–2⋅43; P = 0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long‐term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long‐term outcomes in such patients.
PDF
