Dataset Information

Case Report of a Fatal Serious Adverse Event Upon Administration of T Cells Transduced With a MART-1-specific T-cell Receptor.

ABSTRACT: Here, we describe a fatal serious adverse event observed in a patient infused with autologous T-cell receptor (TCR) transduced T cells. This TCR, originally obtained from a melanoma patient, recognizes the well-described HLA-A*0201 restricted 26-35 epitope of MART-1, and was not affinity enhanced. Patient 1 with metastatic melanoma experienced a cerebral hemorrhage, epileptic seizures, and a witnessed cardiac arrest 6 days after cell infusion. Three days later, the patient died from multiple organ failure and irreversible neurologic damage. After T-cell infusion, levels of IL-6, IFN-?, C-reactive protein (CRP), and procalcitonin increased to extreme levels, indicative of a cytokine release syndrome or T-cell-mediated inflammatory response. Infused T cells could be recovered from blood, broncho-alveolar lavage, ascites, and after autopsy from tumor sites and heart tissue. High levels of NT-proBNP indicate semi-acute heart failure. No cross reactivity of the modified T cells toward a beating cardiomyocyte culture was observed. Together, these observations suggest that high levels of inflammatory cytokines alone or in combination with semi-acute heart failure and epileptic seizure may have contributed substantially to the occurrence of the acute and lethal event. Protocol modifications to limit the risk of T-cell activation-induced toxicity are discussed.

SUBMITTER: van den Berg JH

PROVIDER: S-EPMC4817886 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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Case Report of a Fatal Serious Adverse Event Upon Administration of T Cells Transduced With a MART-1-specific T-cell Receptor.

van den Berg Joost H JH Gomez-Eerland Raquel R van de Wiel Bart B Hulshoff Lenie L van den Broek Daan D Bins Adriaan A Tan Hanno L HL Harper Jane V JV Hassan Namir J NJ Jakobsen Bent K BK Jorritsma Annelies A Blank Christian U CU Schumacher Ton N M TN Haanen John B A G JB

Molecular therapy : the journal of the American Society of Gene Therapy 20150421 9

Here, we describe a fatal serious adverse event observed in a patient infused with autologous T-cell receptor (TCR) transduced T cells. This TCR, originally obtained from a melanoma patient, recognizes the well-described HLA-A*0201 restricted 26-35 epitope of MART-1, and was not affinity enhanced. Patient 1 with metastatic melanoma experienced a cerebral hemorrhage, epileptic seizures, and a witnessed cardiac arrest 6 days after cell infusion. Three days later, the patient died from multiple org ...[more]

PMID: 25896248

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Project description:IntroductionAnticholinergic adverse effects (AEs) are a problem for elderly people. This study aimed to answer the following questions. First, is an analysis of anticholinergic AEs using spontaneous adverse drug event databases possible? Second, what is the main drug suspected of inducing anticholinergic AEs in the databases? Third, do database differences yield different results?MethodsWe used two databases: the US Food and Drug Administration Adverse Event Reporting System database (FAERS) and the Japanese Adverse Drug Event Report database (JADER) recorded from 2004 to 2020. We defined three types of anticholinergic AEs: central nervous system (CNS) AEs, peripheral nervous system (PNS) AEs, and a combination of these AEs. We counted the number of cases and evaluated the ratio of drug-anticholinergic AE pairs between FAERS and JADER. We computed reporting odds ratios (RORs) and assessed the drugs using Beers Criteria®.ResultsConstipation was the most reported AE in FAERS. The ratio of drug-anticholinergic AE pairs was statistically significantly larger in FAERS than JADER. Overactive bladder agents were suspected drugs common to both databases. Other drugs differed between the two databases. CNS AEs were associated with antidementia drugs in FAERS and opioids in JADER. In the assessment using Beers Criteria®, signals were detected for almost all drugs. Between the two databases, a significantly higher positive correlation was observed for PNS AEs (correlation coefficient 0.85, P = 0.0001). The ROR was significantly greater in JADER.ConclusionsThere are many methods to investigate AEs. This study shows that the analysis of anticholinergic AEs using spontaneous adverse drug event databases is possible. From this analysis, various suspected drugs were detected. In particular, FAERS had many cases. The differences in the results between the two databases may reflect differences in the reporting countries. Further study of the relationship between drugs and CNS AEs should be conducted.

Project description:RationaleAdverse drug reactions (ADRs) to iohexol occur infrequently and generally result in good outcomes. This report describes a 51-year-old man suffering from an ADR to iohexol (Omnipaque 300), which proved fatal.Patient concernsThe patient was admitted to hospital due to intermittent dizziness over 2 years and transient numbness and weakness of the right limbs for 1 week. The patient was investigated using carotid artery angioplasty (CAA), during which the patient suffered a sudden disorder of consciousness and a tonic-clonic seizure leading to status epilepticus. After the CAA, the patient suffered from increasing cerebral edema volume.DiagnosesResults of digital subtraction angiography and computed tomography angiography performed at another hospital before the CAA suggested severe stenosis of the left internal carotid artery at the spinal C1 level. In the processes of intraoperative and postoperative CAA, the patient developed severe allergic reactions to the contrast agent including epilepsy, brain tissue edema, and renal failure, which were typical according to the 10th edition of the American College of Radiology Manual on Contrast Media (ACR Manual on Contrast Media, Version 10.3, 2017).InterventionsThe patient was treated with antiepileptic, antianaphylactic therapy, and control of blood pressure. Due to rapid and severe brain edema, a decompressive craniectomy was performed on the left side, but it was unsuccessful in reducing brain edema. Subsequently, the patient was started on continuous renal replacement therapy for progressive renal dysfunction.OutcomesDespite the use of a variety of medical and surgical interventions, it was not possible to control the patient's condition, which gradually declined leading to death, 7 days post-CAA.LessonsTo the authors' knowledge, this represents the 1st case of fatal contrast-induced ADR to iohexol during CAA. Although a variety of preoperative tests for iohexol allergy were performed according to recommendations from the ACR Manual on Contrast Media (Version 10.3, 2017), severe complications related to iodized contrast agent still occurred. If the ADR had been recognized sooner and decompressive craniectomy and continuous renal replacement therapy were applied earlier, it would have improved the patients' prognosis.

Project description:BackgroundSerious cardiovascular adverse events (SCAEs) associated with intravenous sedatives remain poorly characterized.ObjectiveThe objective of this study was to compare SCAE incidence, types, and mortality between intravenous benzodiazepines (i.e., diazepam, lorazepam, and midazolam), dexmedetomidine, and propofol in the USA over 8 years regardless of the clinical setting where it was administered.MethodsThe Food and Drug Administration's MedWatch Adverse Event Reporting System was searched between 2004 and 2011 using the Evidex® platform from Advera Health Analytics, Inc. to identify all reports that included one or more of ten different SCAEs (package insert incidence???1%) and where an intravenous benzodiazepine, dexmedetomidine, or propofol was the primary suspected drug.ResultsAmong the 2326 Food and Drug Administration's MedWatch Adverse Event Reporting System cases reported, 394 (16.9%) were related to a SCAE. The presence of a SCAE (vs. a non-SCAE) is associated with higher mortality (34 vs. 8%, p?<?0.001). The percentage of cases with one or more SCAE, the case mortality rate (%), and the incidence of each SCAE (per 106 days of sedative exposure), respectively, were benzodiazepines (14, 26, 13) [diazepam (13, 23, 31); lorazepam (15, 43, 14); midazolam (14, 20, 11)]; dexmedetomidine (40, 15, 13); and propofol (17, 39, 7). Propofol (vs. either a benzodiazepine or dexmedetomidine) was associated with more total SCAEs (268 vs. 126, p?<?0.001) but a lower incidence (per 106 days of sedative exposure) of SCAE (7 vs. 13, p?=?0.0001) and cardiac arrest [6.3 (benzodiazepine) vs. 6.7 (dexmedetomidine) vs. 1.4 (propofol), p?<?0.0001].ConclusionsSerious cardiac adverse events account for nearly one-fifth of intravenous sedative Food and Drug Administration's MedWatch Adverse Event Reporting System reports. These SCAEs appear to be associated with greater mortality than non-cardiac serious adverse events. Serious cardiac events may be more prevalent with either benzodiazepines or dexmedetomidine than propofol.

Dataset Information

Case Report of a Fatal Serious Adverse Event Upon Administration of T Cells Transduced With a MART-1-specific T-cell Receptor.

Publications

Case Report of a Fatal Serious Adverse Event Upon Administration of T Cells Transduced With a MART-1-specific T-cell Receptor.

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