Haemopoietic Improvement Following Iron Chelation for Transfusional Haemosiderosis in Patients with Haematopoietic Neoplasia and Aplastic Anaemia: An Observational Study

The benefit of iron chelation therapy (ICT) in patients with thalassaemia major is well established; however its role in adults with haematopoietic neoplasia (HN) and aplastic anemia (AA) is less certain. Post hoc analysis of the EPIC study revealed ICT therapy was associated with improved haemopoietic parameters in approximately 20% of patients with myelodysplasia (MDS). Deferasirox has been reported to inhibit NF-kB, a key transcription factor involved in the inflammatory response. We speculate that deferasirox may have an additional action as an immunosuppresive agent.

To identify cases of HN and AA demonstrating haematopoietic improvement following ICT and the factors associated with response.

Multicentre observational study; Physician recall of HN and AA cases showing haemopoietic improvement with ICT.

Eight cases of haemopoietic improvement following ICT were identified: median age 60 (25–68), Male 5. Disorders included: hypoplastic MDS (3), aplastic anaemia (2) refractory anaemia with ringed sideroblasts (1) refractory cytopenia with multilineage dysplasia (1) and idiopathic myelofibrosis (1). All patients were transfusion dependent requiring 3.4 units/month (2.6–6.1) with a median pre-transfusion haemoglobin of 82g/l (66–95) prior to commencement of ICT, and baseline ferritin 1896 mcg/L (1017–5480). Two patients had raised erythrocyte sedimentation rate. All patients received deferasirox: median dose 12 mg/kg/day (5.6–20.6). Seven patients became transfusion independent but all had an erythroid response with median Hb following ICT of 120g/L (85–135). Median time to erythroid response: 96 days (61–450). Four patients received other therapies that may have contributed to their improvement. Six patients had platelet and four neutrophil responses.

Haematological responses occurred prior to significant falls in ferritin and at deferasirox doses considered inadequate for ICT. The over-representation of patients with AA/hypoplastic MDS (5) and presence of raised inflammatory markers in two of three cases without marrow hypoplasia supports the hypothesis that deferasirox may have beneficial immunosuppressive activity and may explain the observed responses in this series. Prospective studies are needed.

Novartis Australia provided support to facilitate discussions related to this topic. The company had no role in analysing the data or preparing the abstract, and its content is responsibility of the authors.

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