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

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-γ, 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.

The efficacy of levobupivacaine, ropivacaine, and bupivacaine for combined psoas compartment-sciatic nerve block in patients undergoing total hip arthroplasty.

BACKGROUND AND OBJECTIVES: The aim of our study was to compare postoperative analgesic efficacy, and the extent of sensory and motor blockade of levobupivacaine, ropivacaine, and bupivacaine administered in a combined psoas compartment-sciatic nerve block (PCSNB) for total hip arthroplasty. METHODS: Forty-five patients undergoing total hip arthroplasty under general anesthesia combined with PCSNB, were randomly assigned to receive either 50 mL levobupivacaine 3 mg/mL, 50 mL ropivacaine 4.5 mg/mL or 50 mL bupivacaine 3 mg/mL with epinephrine. Postoperative, the pain intensity at rest, the degree of motor block (Modified Bromage Scale) and the extent of sensory block (pin prick test) were recorded at 4, 8, 12, 24, and 48 hours following initial injection in a double blind fashion. RESULTS: The postoperative pain intensity was low and did not differ between groups, except for a significantly lower pain intensity in group ropivacaine compared with group levobupivacaine at 4 hours. Five patients (11%), equally divided over three groups, needed parenteral rescue opiates postoperatively. The extent of sensory block was not different between the three groups. In each group the majority of patients showed no sensory block in dermatome L1. Group levobupivacaine initially showed the least motor impairment. Motor impairment was found to be significantly higher in bupivacaine group compared with both ropivacaine and levobupivacaine groups at 12 (P = 0.012) and 48 hours (P = 0.003). CONCLUSIONS: Levobupivacaine, bupivacaine and ropivacaine are equally effective for PCSNB in patients undergoing total hip arthroplasty. Residual pain may be due to the lack of sensory block in dermatome L1, suggesting that modification of this technique should be considered for this type of surgery.