5612976 FIRST ADMINISTRATION OF HYPOXIC BLOOD IN A TRANSFUSION-DEPENDENT PATIENT

Abstract

Background: Many patients with inherited and acquired anemias such as sickle cell disease, thalassemia and myelodysplastic syndromes (MDS) are transfusion-dependent, requiring regularly scheduled red blood cell (RBC) transfusions.1 Chronic transfusions are associated with a range of complications, such as transfusion-related adverse events (AEs) and iron overload.1 Frequent transfusions may also have a negative impact on patient quality of life (QoL)1 and access is often difficult. To reduce transfusion burden in dependent patients, Hemanext Inc. (Lexington, MA, United States) has developed a CE mark certified device to process and store red blood cells hypoxically - CPD/PAGGSM leukocytes-reduced (LR), O2/CO2 reduced.2 By reducing oxidative stress, hypoxic blood storage has been shown to improve the quality and function of RBCs,3 demonstrating that lower volumes of hypoxic RBCs are required to resuscitate from hemorrhagic shock and maintain hemodynamics than conventional RBCs in animal models.4 This may have several benefits in transfusion-dependent patients, including increasing the interval between transfusions and hence potential to reduce iron overload. Aims/Methods: A pilot clinical study in Norway is investigating the safety of a single administration of hypoxic RBCs in patients with hematologic malignancies and patients with burns. The primary outcome of the study is the occurrence of AEs at Day 7±1 post-transfusion. Secondary outcomes include assessment of AEs from enrollment to subsequent RBC transfusion (or Day 28) and the evolution of hemoglobin (Hb) levels pre- and post-transfusion. For the subset of patients with hematologic malignancies, the transfusion trigger is set to Hb <9.0 g/dL, and two units of hypoxic RBCs are administered. Results: In August 2022, following his informed consent, the first patient was transfused with hypoxic RBCs; this patient was also the first to receive hypoxic blood within Hemanext’s overall clinical program. The patient was an 80-year-old man who initially presented with anemia and diagnostic workup revealed bone marrow smear with morphological features of erythroid dysplasia with ring sideroblasts in 30% of cells and mutation in the SF3B1 gene. After initial response to treatment, he became transfusion-dependent, and has received 2 RBC units every 2 weeks for a year. The patient had a pre-transfusion Hb level of 8.1 g/dL and received 2 units of O+ hypoxic RBCs over 2 hours without any complications. No adverse events were recorded on Day 1 and the patient experienced no adverse events by Day 7. Further outcomes will be reported. Conclusion: Hypoxic RBCs processed with the CPD/PAGGSM LR, O2/CO2 reduced system were well tolerated in this patient; Hb level was within the target range at follow-up, supporting that hypoxically stored RBCs function appropriately. The study is ongoing and will continue to assess hypoxic RBCs in patients with hematologic malignancies and patients with burns. Enrolment within the wider clinical program – including studies investigating hypoxic RBC administration in patients with thalassemia in Italy and sickle cell disease in the US – is planned.