Analysis Of Hematological Improvement With Iron Chelation Therapy Using Deferasirox In Subject Ts With Therapy-Refractory Severe Aplastic Anemia

It has been shown that iron chelation therapy (ICT) improves survival and quality life in subjects with transfusion-dependent hematological disorder including aplastic anemia (AA). In most cases of aplastic anemia, hematopoiesis is impaired by immunological disturbance, so the number of CD34+ stem/progenitor cells decreases drastically in severe AA. Little is known, however, about the hematological response to deferasirox therapy in those with severe AA, especially refractory cases with immunosuppressive therapy (IST).

Nine subject 5 men and 4 women aged 20 to 83 (median age: 59.4 years) with transfusional iron overload who were administered the oral iron chelator, deferasirox (DFX) were evaluated from April 2010 to March 2013.at our hospital. Of these, one had non-severe AA, and 8 severe AA classified by severity criteria (Hematology 2011). These 8 were administered immunosuppressive therapy (IST) with rabbit antithymocyte globulin (rATG) in combined with cyclosporine A (CsA), but no hematological improvement was seen.After informed consent was obtained, all 9 were administered iron chelation therapy when serum ferritin (SF) exceeded 1,000 ng/mL or they required over 20 RBC in transfusions (or 100 mL/kg of RBC). Hematological improvements was assessed using International Working Group 2006 criteria.

The initial median DFX dose was 12.0 mg/kg per day and median treatment duration was 13.4 months. Two discontinued treatment. Hematologic improvements was observed in 50% (4/8) of those with severe AA and all 4 no longer required blood transfusions, and while 3 of the remaining 4 no longer required platelet transfusion. Median time to transfusion independence was 4.3 months while that to transfusion independence was 7.2 months In these 4 subject ts, median serum ferritin was 1,708 ng/ml immediately before ICT and decreased to less than 500 ng/ml after ICT. Bone marrow (BM) biopsied was in subjects with hematological improvement, showed that BM cellularity had slightly but significantly recovered in all cases.

ICT using DFX improved hematopoiesis in subjects with severe AA even after IST. This finding suggested that DFX induction should be considered as a potential treatment in IST-refractory severe AA. Thus, DFX appears to support the efficacy of IST due to the chelation of cellular excess iron in BM cells.

No relevant conflicts of interest to declare.