Chronic Red Cell Exchange for the Management of Alpha Thalassemia Major Complicated by Iron Overload

Alpha thalassemia major is a severe hemoglobinopathy characterized by absent or markedly reduced alpha-globin production, necessitating lifelong blood transfusions. Chronic simple transfusions can lead to significant iron overload, often requiring iron chelation therapy. However, some patients are unable to tolerate chelation or chelation is insufficient, highlighting the need for alternative strategies for managing iron overload. This study is one of the first to evaluate the feasibility, safety, and efficacy of red blood cell exchange (RBCX) as a therapeutic option for managing iron overload while improving hemoglobin function in an alpha thalassemia major patient with iron overload despite chelation therapy. RBCX therapy was performed approximately every 3 weeks over 1 year, with frequent adjustment of exchange parameters to meet pre-transfusion target levels of functional hemoglobin. Serum ferritin levels, hemoglobin electrophoresis, and functional hemoglobin levels were tracked with each exchange transfusion. For each RBCX treatment, variant hemoglobins decreased by 3.8-fold (from 19.9% to 8.9%) and functional hemoglobin levels increased approximately 3.0 g/dL. RBCX was well tolerated and associated with a marked reduction in systemic iron burden, with serum ferritin declining 7.4-fold (86.4%) over 1 year of therapy, followed by a rise after cessation of RBCX. Cardiac iron remained within normal limits throughout the study period. In contrast, liver iron demonstrated a transient increase shortly after initiation of RBCX, but ultimately declined to levels below baseline after 1 year, even during a period in the absence of iron chelation. These findings suggest that RBCX exerts a meaningful effect on iron homeostasis and raises the possibility of a synergistic benefit when combined with iron chelation. This case highlights that RBCX is a viable therapeutic strategy to treat iron overload in patients with alpha thalassemia major.