Background: Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder. Immunosuppressive therapy or allogeneic stem cell transplantation (SCT) are recommended depending on severity of the disease, patient's age and availability of donor. In addition, many patients require blood transfusions as supportive management, which lead to the development of iron overload. Previous studies have shown a negative impact of pretransplant iron overload on overall survival (OS), mortality, and infection in patients undergoing allogeneic stem cell transplantation (SCT). Although the use of oral iron-chelating agent, deferasirox, has been increased, the impact of pretransplant iron chelating therapy (ICT) on the transplant outcomes in patients with SAA was uncertain.

Methods: This study included 109 iron overloaded patients with SAA who underwent allogeneic SCT between March 2002 and December 2012. All patients had available pretransplant serum ferritin data. Among them, 50 patients were received pretransplant ICT with deferasorox, when their serum ferritin was more than 1000 ¥ìg/L, whereas 59 patients had more than 1000 ¥ìg/L of serum ferritin but did not received ICT (era before availability of deferasirox).

Results: Fifty-five men and 54 women were assessed. Their median age was 34 years (range, 15-59 years). The patients received grafts from either a HLA identical sibling (N=55) or an unrelated donor (N=54). Primary engraftment was achieved in all, but 5 patients developed secondary graft failure. After a median follow-up of 38.3 (range, 6.1-124.9) months for survivors, there was not statistical difference of overall survival (OS) between the patients with ICT and those without ICT (82.3% vs 89.9%, P=0.455). Of note, the possible survival benefit of pretransplant ICT was observed in unrelated transplant setting (93.5% vs. 78.3%, P=0.090). Pretransplant ICT group showed a lower infection rate after SCT compared to those without ICT (34% vs. 59%, P=0.008). For 50 patients receiving pretransplant ICT with deferasirox, median serum ferritin levels decreased from 1995 ¥ìg/L at the initiation of ICT to 1240 ¥ìg/L before SCT. Median duration of ICT before SCT was 3.6 months (range, 0.3-44.2 months), and mean daily dose was 14.8 mg/kg per day. The patients who achieved more than 650 ¥ìg/L decrement of serum ferritin levels from ICT initiation to SCT had a higher OS than the patients with less than 650 ¥ìg/L (96.7% vs. 80.0%, P=0.044).

Conclusion: These results indicate that iron overload was associated with a negative impact on outcome after SCT in SAA. Pre-SCT ICT can reduce the incidence of infection after SCT and the possible survival benefit of Pre-SCT ICT was present especially in unrelated donor SCT. Among the patients receiving pretransplant ICT, significant decrement of serum ferritin is a favorable prognostic factor after allogeneic SCT in iron-overloaded patients with SAA


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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