Iron Chelation with Deferasirox in Thalassemia Major Patients with Low Iron Burdens and Moderate to High Transfusion Regimens.

A worldwide multicenter clinical trial of deferoxamine (DFO) in comparison to deferasirox (DFX/Exjade) established optimal therapeutic doses of DFX for use in b-thalassemia patients (pts) with moderate to severe iron burdens as determined by serum ferritin levels greater than 1000 ng/mL and liver iron concentrations (LICs) greater than 3 mg/g-dry weight (dw) resulting from regular red blood cell (RBC) transfusion regimens designed to maintain pre-tx hemoglobin (Hgb) levels greater than 9 to 10 gm/dL. To date, the use of DFX in less heavily iron overloaded transfused patients is not well documented. Therefore, we studied the safety and efficacy of DFX at a dose of approximately 20 mg/kg/day in a group of regularly transfused thalassemia major pts who had previously been well chelated with subcutaneous (sc) DFO as evidenced by serum ferritin levels less than 1000 ng/mL and LICs less than 3 mg/gm-dw.

The pt group consisted of eight transfusion dependent thalassemia major pts (2M/6F) who ranged in age from 13 to 49 yrs (mean ± SEM 28.3 ± 13.2 yrs). Six of the pts were splenectomized (2M/4F) and maintained on moderate to high transfusion regimens (2 to 4 RBC units per month) so as to maintain a pre-tx Hgb level of 9 to 10 gm/dL.

Clinical parameters, including pre-tx Hgb levels, RBC units transfused, serum ferritins, liver function tests (ALT/AST), and renal function studies (BUN/creatinine) were determined at baseline and monitored monthly thereafter in all patients for one year. Hearing tests, eye exams and determinations of LIC by T2* magnetic resonance imaging (MRI) were done at baseline and 12 months. Annual tx requirements were calculated and expressed as mL of RBCs/kg/yr. All pts previously infused DFO sc 5 days each week at doses of 40 to 60 mg/kg/day. During the study, they ingested DFX daily 30 minutes prior to breakfast at a dose of 20 to 30 mg/kg as a suspension in water, apple or orange juice. Dose adjustments were made depending upon trends in serum ferritin levels, liver function tests or renal studies.

Each pt received 2 to 4 leukocyte depleted washed RBC units per month (mean 119 ± 8.2 mL/kg/yr). Their mean pre-tx Hgb levels were 9.7 ± 0.2 gm/dL. Average monthly chemistry parameters were as follows: serum ferritin = 550 ± 9.4 ng/mL; AST = 36 ± 5; ALT = 36 ± 7; BUN = 14.8 ± 1.0; creatinine = 0.7 ± 0.1. There were no significant changes in the parameters related to liver or renal function, or in LICs during the 12-month observation period, the mean LICs were 2.0 ± 0.4 mg/gm-dw at baseline vs. 1.6 ± 0.3 mg/gm-dw at 12 months. Serum ferritin levels also remained stable during the course of therapy (577 ± 71 ng/mL at baseline vs. 480 ± 106 ng/mL at 12 months). The starting dose of DFX ranged from 20 to 30 mg/kg/day. Over the course of the study, the dose was increased to 25 and 30 mg/kg/day in pts 2 and 7, respectively, owing to a progressive increase in serum ferritin levels and decreased to 10 mg/kg in pt 3 and 18 mg/kg in pt 8 due to declining ferritin levels. On average, a dose of 20.5 ± 2 mg/kg/day was needed to maintain iron balance. No serious adverse events occurred during the 12-month course of DFX and no significant side effects (e.g. rash or gastrointestinal symptoms) were reported.

Moderate doses of DFX, slightly more than 20 mg/kg/day, were safe and effective in maintaining iron balance as measured by LICs (MRI) and serum ferritin levels in thalassemia major patients with low iron burdens (LICs <3 mg/g-dw and serum ferritin levels <1000 ng/mL) receiving regular tx therapy to maintain pre-tx Hgb levels of 9 to 10 gm/dL.

No relevant conflicts of interest to declare.