Loss of Transfusion Dependency Following Deferasirox Treatment of Iron Overload in a Woman with Myelofibrosis and Spherocytosis - a Case Report

Tesch, Hans; Ihling, Christian

doi:10.1159/000349939

Cited by 10 publications

(7 citation statements)

References 24 publications

(27 reference statements)

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“…As a consequence, this medication is now commonly employed in the real‐life management of these patients. Conversely, there were scarce and erratic data concerning the use of DFX in patients with FP‐MPN and transfusional iron overload prior to this report . Similar observations to those presented in our data set have been observed in some case reports and more recently in a small single‐center study .…”

Section: Discussionsupporting

confidence: 88%

Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase

Latagliata

Montagna

Porrini

et al. 2015

European J of Haematology

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At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1-43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra-hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients.

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Section: Discussionsupporting

confidence: 88%

Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase

Latagliata

Montagna

Porrini

et al. 2015

European J of Haematology

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“…Several emerging lines of evidence actually indicate that ICT can improve hematopoiesis and leads to a reduction or abolition of transfusion dependence in PMF 26–29,32. Therefore these data are very sparse and mainly deriving from single case descriptions, but they are suggestive of a real biological phenomenon.…”

Section: Discussionmentioning

confidence: 99%

“…As compared to other iron chelators, DSX is a potent NF-kB inhibitor and is able to increase glutathione (GSH) in red blood cells, thus protecting them from oxidative insults 25. Despite these observations, the role of ICT in PMF remains largely undefined, and a few reports are present in the literature regarding this specific setting of Philadelphia-negative chronic myeloproliferative neoplasm (MPN Ph-),26–29 reflecting the limited expertise in this field. Few data have shown a survival benefit associated with the use of ICT in patients with TD anemia and PMF,29 similar to MDS, but more importantly there are no sufficient studies that have examined the effectiveness in terms of hematological response, particularly erythroid response, together with the safety profile in patients with PMF.…”

Section: Introductionmentioning

confidence: 99%

“…Despite these observations, the role of ICT in PMF remains largely undefined, and a few reports are present in the literature regarding this specific setting of Philadelphia-negative chronic myeloproliferative neoplasm (MPN Ph-),26–29 reflecting the limited expertise in this field. Few data have shown a survival benefit associated with the use of ICT in patients with TD anemia and PMF,29 similar to MDS, but more importantly there are no sufficient studies that have examined the effectiveness in terms of hematological response, particularly erythroid response, together with the safety profile in patients with PMF. Here we reported our experience in TD-PMF patients treated with DSX from September 2010 to December 2013, in order to evaluate the efficacy and safety profile of this approach in MPN Ph- setting.…”

Section: Introductionmentioning

confidence: 99%

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Iron Chelation Therapy With Deferasirox in the Management of Iron Overload in Primary Myelofibrosis

Elli

Belotti

Parma

et al. 2014

Mediterr J Hematol Infect Dis

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Deferasirox (DSX) is the principal option currently available for iron-chelation-therapy (ICT), principally in the management of myelodysplastic syndromes (MDS), while in primary myelofibrosis (PMF) the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day), with 3 transient interruption of treatment for drug-related adverse events (AEs) and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%), 2 of them (20%) obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin) were greater in hematologic responder (HR) compared with non-responder (NR) patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP). Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP. However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required.

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“…The occurrence of anemia and transfusion dependency at diagnosis of PMF heralds a shortened survival [3]. Iron overload as a result of repeated transfusion of red blood cells (RBC) has been linked to systemic damage of liver, heart and endocrine organs [2,4].…”

Section: Introductionmentioning

confidence: 99%

Transfusion Independency and Histological Remission in a Patient with Advanced Primary Myelofibrosis Receiving Iron-Chelation Therapy with Deferasirox

et al. 2016

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Background: Iron overload is a common problem in patients with primary myelofibrosis and anemia due to transfusion dependency. This results in organ damage and toxic effects on hematopoietic cells in the bone marrow. At present, iron chelation therapy is not recommended in patients with myeloproliferative syndromes. Case Report: We describe a very interesting development in a patient with primary myelofibrosis receiving iron chelation. Transfusion independency and a nearly complete histological remission of the underlying disease occurred within a few weeks of therapy. In addition, a change in molecular genetic findings was observed. Initially a JAK2 and a U2AF1 mutation were detected in the core biopsy. During and after therapy the U2AF1 mutation progressed, whereas the JAK2 mutation could no longer be verified. Conclusion: The improvement in hematopoiesis might results from reduction of oxidative stress on hematopoietic progenitor cells or other unclear deferasirox-mediated effects, whereas the reason for the change in molecular genetic findings is unclear. It appears that deferasirox might have a modulating effect on JAK2-kinase mutations. However, further investigation of selective molecular suppression properties of deferasirox are warranted.

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Loss of Transfusion Dependency Following Deferasirox Treatment of Iron Overload in a Woman with Myelofibrosis and Spherocytosis - a Case Report

Cited by 10 publications

References 24 publications

Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase

Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase

Iron Chelation Therapy With Deferasirox in the Management of Iron Overload in Primary Myelofibrosis

Transfusion Independency and Histological Remission in a Patient with Advanced Primary Myelofibrosis Receiving Iron-Chelation Therapy with Deferasirox

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