Procalcitonin as a biomarker for predicting bacterial infection in chimeric antigen receptor T-cell therapy recipients.

BACKGROUND: It is unknown whether serum procalcitonin (PCT) concentration monitoring can differentiate between bacterial infection or cytokine release syndrome (CRS) when chimeric antigen receptor T-cell (CAR-T) recipients present with a constellation of signs and symptoms that may represent both complications. OBJECTIVE: The objective of the study was to assess the utility of serum PCT concentrations as a biomarker of bacterial infection in CAR-T recipients. STUDY DESIGN: This single-center, retrospective, medical record review evaluated patients prescribed CAR-T therapy until death or 30 days after infusion. Logistic regression modeling determined the association between elevated serum PCT concentrations within 48 h of fever onset and microbiologically confirmed infection. Secondary outcomes included clinically suspected infection, CAR-T toxicity rates, and broad-spectrum antibiotic usage. Predictive performance of PCT was assessed by area under the receiver operating characteristic curve (AUC). RESULTS: The 98 included patients were a median age of 63 (IQR: 55-69) years old, 47 (48%) were male, and 87 (89%) were Caucasian. Baseline demographics and clinical characteristics were similar between patients with and without a bacterial infection. Serum PCT >0.4 ng/mL within 48 h of fever was significantly associated with a microbiologically confirmed bacterial infection (OR: 2.75 [95% CI: 1.02-7.39], p = 0.045). Median PCT values in patients with and without confirmed infections were 0.40 ng/mL (IQR: 0.26, 0.74) and 0.26 ng/mL (IQR: 0.13, 0.47), respectively. The AUC for PCT to predict bacterial infection was 0.62 (95% CI 0.48-0.76). All patients experienced CRS of some grade, with no difference in CRS severity based on elevated PCT. Broad-spectrum antibiotics were used for a median of 45% and 23% of days in those with and without confirmed infection, respectively (p = 0.075). CONCLUSION: Elevated serum PCT concentrations above 0.4 ng/mL at time of first fever after CAR-T infusion was significantly associated with confirmed bacterial infection. Furthermore, rigorous, prospective studies should validate our findings and evaluate serial PCT measurements to optimize antimicrobial use after CAR-T therapy.

Assessment of Opioid Cross-reactivity and Provider Perceptions in Hospitalized Patients With Reported Opioid Allergies.

Background: The incidence of opioid allergy cross-reactivity in hospitalized patients with historical opioid allergies remains unknown. Objectives: The purpose of this study was to characterize the incidence of newly suspected IgE-mediated reactions (IMRs) based on clinical criteria among patients with a chart-documented opioid allergy and to assess clinician perceptions of opioid allergies. Methods: This retrospective cohort study was conducted in hospitalized adults with a historically documented opioid allergy who received a subsequent opioid. The primary outcome was the incidence of allergic cross-reactivity between clinical and chemical opioid classes in patients with historical IMRs (H-IMRs) identified by clinical criteria, ICD-9 diagnosis codes, or allergic reaction treatment. Secondary outcomes included the incidence of opioid intolerances incorrectly documented as allergies and a survey to clinicians to assess the impact of opiate warnings on prescribing practices. Results: A total of 499 patients with historical opioid allergies were included. H-IMR to an opioid of any class was not significantly associated with IMR cross-reactivity to the same or any other class, with cross-reactivity rates ranging from 0% to 6.7%. Of the historical chart-documented allergies, 249 reactions (50%) were determined to be intolerances. A total of 461 (92.5%) patients successfully tolerated readministration of opioids despite a chart-documented allergy, and 8 (1.6%) patients developed possible IMR (7 pruritus, 1 possible anaphylaxis). Survey results (n = 54) indicated that opiate allergy warnings were neutral or unlikely to change opiate prescribing. Conclusions: The risk of IMRs caused by opioids is low in patients with H-IMRs to opioids. Opioid allergy documentations may propagate alert fatigue and unwarranted prescribing changes.