Efficacy of Deferasirox on Iron Chelation in Thalassemia Patients After Hematopoietic Stem Cell Transplantation

Severe b thalassemia disease can be cured by hematopoietic stem cell transplantation (HSCT). Iron overload is one of the complications after HSCT in these patients. To prevent further tissue damages from excessive iron in the body, iron chelation is recommended in ex-thalassemics. Phlebotomy is an effective procedure removing iron excess in post HSCT thalassemia patients. However, the limitations of phlebotomy exist including young children, difficult access to peripheral veins, mixed chimerism, and non-compliance. Deferasirox has been shown to be an effectively oral iron chelator in transfusion-dependent thalassemia patients. The efficacy of deferasirox on iron removal in post HSCT survivors is limited.

To compare the efficacy of iron chelation between deferasirox and phlebotomy in post HSCT thalassemia patients

We included patients with severe b thalassemia who had received related or unrelated donor HSCT at least one year. The patients had no evidence of chronic GVHD or taking immunosuppressive agent at least 6 months. Twenty four patients were randomized into deferasirox or phlebotomy arm (12 patients each). The patients in deferasirox arm received deferasirox starting at the dose of 20 mg/kg/day. Adverse drug reactions were recorded. The dose of deferasirox was adjusted if severe side effects were recognized. The patients in phlebotomy arm underwent monthly 10 mL/kg blood withdrawal with normal saline replacement. Symptoms of hypotension and blood pressure were monitored during the procedure. Laboratory investigations including CBC, LFT, BUN, creatinine, and urinalysis were determined every month. Serum iron, total iron binding capacity and ferritin were measured every 3 months.

The median age, M :F, types of thalassemia, and severity class were not different between two groups. In deferasirox group, the median dose of deferasirox was 18.9 mg/kg/day (range, 10 – 21.6 mg/kg). Two patients had reduced deferasirox dosage due to rising creatinine and GI symptoms. The baseline median (range) of alanine transaminase (ALT), transferrin saturation (TS), and ferritin were 68 U/L (14 – 332 U/L), 87.9% (35.6 – 106.1%), and 2, 802.9 (1, 332 – 6, 628.4 mg/dL) in deferasirox group and 53.5 U/L (32 – 78 U/L), 70.9 % (36.5 – 96.6%), and 1, 740 (1, 246.4 – 5, 780 mg/dL) in phlebotomy group. The 12-month median (range) of ALT, TS, and ferritin were 37.5 (12 – 508 U/L), 39.5% (28.3 – 70.6%), and 1, 743.5 mg/dL (721.1 – 3555.9 mg/dL) in deferasirox group and 40.5 U/L (27 – 97), 39.2% (22.2 – 95.2%), and 896.2 mg/dL (345.1 – 3, 740 mg/dL) in phlebotomy group. The median changes of ALT, TS, and ferritin at 12-month from baseline of these two groups were not different (Table 1).

Deferasirox was well tolerated and had manageable side effects in ex-thalassemics. Deferasirox reduced serum ferritin as effectively as phlebotomy in thalassemia patients after HSCT.

No relevant conflicts of interest to declare.