Background: Early plasma transfusion is life-saving for bleeding trauma patients. Freeze-dried plasma (FDP) provides unique formulation advantages for infusion in the prehospital setting. We describe characterization and clinical safety data of the first, next-generation FDP stored in plastic bags with rapid reconstitution. Study design and methods: Coagulation and chemistry parameters on 155 pairs of fresh frozen plasma (FFP) and their derivative FDP units were compared. Next, a first-in-human, dose-escalation safety evaluation of FDP, involving 24 healthy volunteers who donated either whole blood or apheresis plasma to create autologous FDP, was performed in three dose cohorts (270, 540, and 810 ml) and adverse events (AEs) were monitored. Cohort 3 was randomized, double-blind with a cross-over arm that compared FDP versus FFP using descriptive analysis for AEs, coagulation, hematology, and chemistry parameters.Results: FDP coagulation factors, clotting times, and product quality (pH, total protein, and osmolality) post-lyophilization were preserved. FDP infusions, of up to 810 ml per subject, were found to be safe and with no serious
Measurement of ionized calcium levels by the technic of Soulier during massive transfusion of ACD blood supplemented with various quantities of calcium led to the apparently erroneous conclusion that ionized calcium levels would rise in the recipient when each unit was supplemented with 0.6 g CaCl2, the quantity which restores normal ionized calcium levels in vitro.
Measurement of ionized calcium activity with the Orion electrode indicates that this ratio of CaCl2 will maintain an approximately normal ionized calcium level in dog recipients if it is infused simultaneously with the blood. Based on this information, it appears reasonable to assume that heparinized ACD blood, recalcified with 0.6 g CaCl2 per unit, may be used to prime the extracorporeal circuit for open heart surgery with the confidence that it will not alter the ionized calcium activity of the patient's blood.
Addition of calcium to the circulation following administration of ACD blood causes a sharp rise and then a fall in the recipient's level of ionized calcium. Further studies in a variety of situations are required before final guidelines can be formulated for supplementation of ACD blood with calcium in massive transfusion.
10040 Background: Combination therapies may improve clinical outcomes in pediatric pts with tumors with single-agent resistance. Emerging preclinical and clinical data have shown a positive effect for combination PARP/immune checkpoint inhibition. The SCOOP study was designed to evaluate combination nir+dost in pediatric pts with non-central nervous system (CNS) RR solid tumors. Herein we present the safety, dose-limiting toxicities (DLTs), PK, and recommended phase 2 dose (RP2D) of nir+dost. Methods: SCOOP is a phase 1, multicenter, open-label, dose-escalation, and cohort-expansion study in pts aged ≥6 mo to <18 y with non-CNS tumor types reported to have a BRCAness gene signature. Part 1A comprised multiple dose-level cohorts (0, 1A, 1B, and 2; Table) of pts ≥20 kg able to swallow nir tablets. The primary endpoint was determination of the RP2D of nir+dost based on DLT incidence during the first 2 cycles. Plasma concentrations were compared with simulated adult concentrations using population PK models. Results: A total of 23 pts with non-CNS RR solid tumors were enrolled with 16 evaluated for DLTs and 23 for PK analysis (see Table for dose-level cohorts and observed DLTs). Grade (Gr) ≥3 drug-related (DR) treatment-emergent adverse events (TEAEs) in part 1A included hematologic toxicities, decreased appetite, and fatigue, with DR serious TEAEs of immune-mediated encephalitis, headache, nausea, vomiting, cerebral hemorrhage, and hyponatremia. Observed plasma nir concentrations at 100 and 200 mg once daily (QD) in pediatric pts were similar to simulated adult concentrations at 200 or 300 mg QD. Observed dost concentrations at 7.5 mg/kg every 3 weeks (Q3W) in pediatric pts were in the expected range for adults at 500 mg Q3W. Conclusions: Observed DLTs were consistent with the individual safety profile of each drug; overall no unexpected safety issues were observed. Based on these results, nir 100 mg QD + dost 7.5 mg/kg Q3W was selected as the RP2D for the SCOOP expansion cohorts in neuroblastoma and osteosarcoma. Pts in the expansion study will receive nir+dost at the RP2D until disease progression. Clinical trial information: NCT04544995 . [Table: see text]
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