In this PACULit recap for PACUPod, Britany and Seth review a post hoc analysis of a double‑blind, placebo‑controlled randomized trial comparing thalidomide to placebo in 100 transfusion‑dependent beta-thalassemia major patients. The discussion covers thalidomide's impact on red blood cell lifespan (measured by biotin labeling), reticulocyte counts, and hemolysis markers (LDH, MCV, Hb), with significant and durable extensions of RBC lifespan up to 48 weeks. The hosts explore potential mechanisms such as fetal hemoglobin induction and immunomodulation, safety considerations (neuropathy, thromboembolism, drug interactions), and the potential to reduce transfusion burden and improve iron homeostasis. They also place the findings in the broader literature context, discuss limitations, and consider future directions including combination strategies with agents like luspatercept.