Liberal versus restrictive red blood cell transfusion strategies in leukemia: protocol for a pilot randomized controlled trial using bleeding-related biomarker endpoints

Acute leukemia is a hematologic malignancy characterized by anemia and thrombocytopenia, leading to a high risk of bleeding complications. Patients with acute leukemia frequently require blood transfusions, particularly during chemotherapy. Current transfusion practice typically maintains hemoglobin concentrations at ≥ 7–8 g/dL; however, a more liberal transfusion strategy aiming for near-normal hemoglobin levels may improve hemostasis by preserving endothelial integrity, improving coagulation and fibrinolysis, and reducing inflammation. This pilot trial will primarily determine the feasibility of conducting a larger randomized trial and will secondarily explore the biological effects of a liberal transfusion strategy on these endpoints. This single-center, pilot randomized clinical trial will recruit 60 participants from an academic hospital in Canada. Participants will be randomized to receive blood transfusions targeting either the standard hemoglobin threshold (7–8 g/dL) or a higher threshold (11 g/dL) at the start of, or within 5 days of initiating, induction chemotherapy. Patients will be followed during their hospital admission for up to 30 days. The primary outcomes are feasibility measures: recruitment (consent and screen-failure rates) and protocol adherence (adherence to the assigned transfusion strategy and to the study schedule). Secondary outcomes include the estimated effect of the transfusion strategy on prespecified biomarkers of endothelial integrity (von Willebrand factor antigen and microalbuminuria-to-creatinine ratio), inflammation (C-reactive protein), and coagulation/fibrinolysis (fibrinogen activity), as well as blood product administration, bleeding events, and quality of life. This pilot trial will provide feasibility and biomarker data to inform the design of a larger trial evaluating the effect of a liberal transfusion strategy on bleeding outcomes in acute leukemia. This research program will enhance supportive care for patients and address an evidence gap in transfusion guidelines for this high-risk population. Registered on Clinicaltrials.gov: NCT06947044. URL: https://clinicaltrials.gov/study/NCT06947044 . Date of registration: 19-04-2025.