CD19-directed chimeric antigen receptor (CAR) T cells show characteristic proliferation kinetics after infusion that correlate with response. Clearance of circulating disease, B-cell aplasia (BCA), and cytokine release syndrome (CRS) are used to observe CAR T-cell function, given the lack of commercial CAR T-cell measurement assays. We investigated the utility of common hematology laboratory parameters in 166 patients with B-cell acute lymphoblastic leukemia (B-ALL) who were treated with CAR T-cell therapy targeting CD19. CAR T-cell infusion was followed by disappearance of circulating blasts in 86% of patients at a median of 6 days. After a lag phase, there was a rapid expansion in absolute lymphocyte count (ALC) in the second week that coincided with the appearance of atypical lymphocytes. The expansion phase was followed by a contraction phase with a concomitant decrease in atypical lymphocytes. In vitro CAR T-cell studies showed similar kinetics and morphological changes. Peak ALC and overall expansion was greater in sustained responders compared with that in nonresponders. Patients with early loss of BCA and those with eventual CD19+ minimal residual disease/relapse showed lower overall lymphocyte expansion compared with the controls. Pleomorphic lymphocytosis was noted in the cerebrospinal fluid at post-CAR time points. We conclude that lymphocyte counts and differential can also be used to evaluate CAR T-cell expansion after infusion, along with BCA and CRS. This is the first report to characterize the morphology of CAR T cells and determine the utility of lymphocyte kinetics.
Objectives Buprenorphine is a highly effective medication for the treatment of opioid use disorder, but it can cause precipitated withdrawal (PW) from opioids. Incidence, risk factors, and best approaches to management of PW are not well understood. Our objective was to describe adverse outcomes after buprenorphine administration among emergency department (ED) patients and assess whether they met the criteria for PW. Methods This study is a case series using retrospective chart review in a convenience sample of patients from 3 hospitals in an urban academic health system. This study included patients who were reported by clinicians as potential cases of PW. Relevant clinical data were abstracted from the electronic health record using a structured retrospective chart review instrument. Results A total of 13 cases were included and classified into the following 3 categories: (1) PW after buprenorphine administration consistent with guidelines (n = 5), (2) PW after deviating from guidelines (n = 4), and (3) protracted opioid withdrawal with no increase in Clinical Opiate Withdrawal Scale score (n = 4). A total of 11 patients had urine drug testing positive for fentanyl, and 11 patients received additional doses of buprenorphine for symptom management. Of the patients, 5 had self‐directed hospital discharges, and 6 were ultimately discharged with prescriptions for buprenorphine. Conclusions Cases of adverse outcomes after buprenorphine administration in the ED and hospital meet criteria for PW, although some cases may have represented protracted opioid withdrawal. Further investigation into the incidence, risk factors, management of PW as well as patient perspectives is needed to expand and sustain the use of buprenorphine in EDs and hospitals.
Background and Aims: Fentanyl is involved in most US drug overdose deaths and its use can complicate opioid withdrawal management. Clinical applications of quantitative urine fentanyl testing have not been demonstrated previously. The aim of this study was to determine whether urine fentanyl concentration is associated with severity of opioid withdrawal. Design: This is a retrospective cross-sectional study. Setting: This study was conducted in 3 emergency departments in an urban, academic health system from January 1, 2020, to December 31, 2021. Participants: This study included patients with opioid use disorder, detectable urine fentanyl or norfentanyl, and Clinical Opiate Withdrawal Scale (COWS) recorded within 6 hours of urine drug testing. Measurements: The primary exposure was urine fentanyl concentration stratified as high (>400 ng/mL), medium (40-399 ng/mL), or low (<40 ng/mL). The primary outcome was opioid withdrawal severity measured with COWS within 6 hours before or after urine specimen collec-tion. We used a generalized linear model with γ distribution and log-link function to estimate the adjusted association between COWS and the exposures. Findings: For the 1127 patients in our sample, the mean age (SD) was 40.0 (10.7), 384 (34.1%) identified as female, 332 (29.5%) reported their race/ethnicity as non-Hispanic Black, and 658 (58.4%) reported their race/ethnicity as non-Hispanic White. For patients with high urine fentanyl concentrations, the adjusted mean COWS (95% confidence interval) was 4.4 (3.9-4.8) compared with 5.5 (5.1-6.0) among those with medium and 7.7 (6.8-8.7) among those with low fentanyl concentrations. Conclusions: Lower urine fentanyl concentration was associated with more severe opioid withdrawal, suggesting potential clinical applications for quantitative urine measurements in evolving approaches to fentanyl withdrawal management.
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