The ‘αO2-PRBCThal’ trial on the use of hemanext One® for blood transfusion support transfusion-dependent thalassemia

Abstract Introduction: Patients with transfusion dependent thalassemia (TDT) are regularly transfused every two to four weeks. Red blood cells' (RBCs) established standard long-term storage methods lead to donor-dependent biochemical and morphological changes in RBCs, collectively termed as “storage lesions”. The HEMANEXT ONE RBC Processing and Storage system limits oxygen, which fuels oxidative damage, aiming in preserving high quality RBCs over longer storage time. HEMANEXT ONE has not been studied in chronically transfused individuals. The aim of our study is to investigate whether RBCs' storage under hypoxic conditions with the HEMANEXT ONE method is at least non-inferior to standard methods in regard to safety and efficacy in providing transfusion support to TDT patients.Methods: This is an open-label, observational study (NCT07055503). The trial will include adult patients followed at the Thalassemia Units either of the First Department of Pediatrics National and Kapodistrian University of Athens (NKUA) or at the LAIKON General Hospital. Patients need to fulfil the following criteria:(i) documented diagnosis of β-TDT defined as receiving ≥ 6 RBC units/24 weeks and no transfusion-free period for ≥ 42days during 24 weeks, (ii) available transfusion history for at least 6 months (iii) chelation and other chronic therapies at a stable dose, all for at least 6 months prior to enrollment. The exclusion criteria included (i) a history of any significant medical condition, laboratory abnormality, or psychiatric illness; (ii) a positive Coombs (antiglobulin) test within 6 months prior to enrollment; (iii) planned or recent splenectomy (within 6 months prior to enrollment); (iv) use of luspatercept within 6 months prior to enrollment or at any time during the study; and (v) participation in an interventional clinical trial or use of investigational medications within 6 months prior to enrollment or during the study period.The study aims to assess changes in the transfusion burden, the degree of hemolysis and the presence of metabolic disturbances. The Primary Endpoint is defined as changes from baseline in RBC transfusion burden, with changes of 20% (corresponding to at least 1 unit/24weeks) from baseline being considered significant. The treatment phase consists of six months, during which the patient will receive PRBC prepared by HEMANEXT ONE methodology and will be compared to a pre-treatment six-months period of receiving RBCs stored by standard methods.Results: Two sites in Greece will participate in the trial and the targeted enrollment is at least 26 evaluable patients. The study is currently enrolling participants, with first patient enrolled in Apr 2025. Enrolment is expected to be completed by Q4, 2025.Conclusions: Overall, hypoxic storage seems to offer advantages in mitigating oxidative stress, without promoting RBC lysis. The ‘αO2-PRBCThal’ trial may provide evidence that the HEMANEXT ONE RBC storage method is both safe and able to provide transfusion support to TDT patients without increasing the transfusion burden, the degree of hemolysis and the metabolic disturbances. Should the hypothesis of non-inferiority be proven, this method may be applicable in routine clinical practice especially when longer RBC storage is required.