Summary: Cytokine release syndrome (CRS) and consumptive coagulopathy can complicate the treatment with chimeric antigen receptor T (CAR‐T) cells. The modified version of the Endothelial Activation and Stress Index (mEASIX), a score derived from haematopoietic stem cell transplantation, combines platelets, C‐reactive protein (CRP), and lactate dehydrogenase (LDH) and has been correlated with CRS and endothelial biomarkers. In 38 consecutive patients with aggressive lymphoproliferative disease we measured a coagulative laboratory panel at baseline and early after infusion of anti‐CD19 CAR‐T. The panel was investigated also in the presence of CRS graded 2 or higher, or immune effector cell‐associated neurotoxicity syndrome (ICANS). Moreover, we examined the relationship between mEASIX, coagulation biomarkers, and toxicities of CAR‐T cells. During CRS grade 2 or higher, we found increased prothrombin time (PT) and activated partial thromboplastin time (aPTT), fibrinogen, D‐dimer, factor VIII (FVIII), and von Willebrand factor (vWF) antigen levels, and decreased platelet count and antithrombin levels. The occurrence of immune effector cell‐associated neurotoxicity syndrome was associated with higher PT values, D‐dimer, FVIII, and vWF levels, and decreased fibrinogen levels and platelet count. A higher mEASIX score correlated with increased aPTT values, fibrinogen, D‐dimer, FVIII and vWF levels, and decreased antithrombin levels. Baseline mEASIX was predictive for consumptive coagulopathy and CRS graded 2 or higher, and for progression‐free survival and overall survival.

Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19–caused mortality (33.3% vs 14.2% [P = .379]). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022]). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729.

Impaired function of hematopoiesis after treatment with chimeric antigen T‐cells (CAR‐T) is a frequent finding and can interest a wide range of patients, regardless of age and underlying disease. Trilinear cytopenias, as well as hypogammaglobulinemia, B‐cell aplasia, and T‐cell impairment, can severely affect the infectious risk of CAR‐T recipients, as well as their quality of life. In this review, we provide an overview of defects in hematopoiesis after CAR‐T, starting with a summary of different definitions and thresholds. We then move to summarize the main pathogenetic mechanisms of cytopenias, and we offer insight into cytomorphological aspects, the role of clonal hematopoiesis, and the risk of secondary myeloid malignancies. Subsequently, we expose the major findings and reports on T‐cell and B‐cell quantitative and functional impairment after CAR‐T. Finally, we provide an overview of current recommendations and leading experiences regarding the management of cytopenias and defective B‐ and T‐cell function.