Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia

Henter, Jan‐Inge; Karlén, Jonas

doi:10.1182/blood-2007-02-065805

Cited by 60 publications

(36 citation statements)

References 22 publications

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“…Concurrent lymphopenia, considered an ominous sign in drug‐induced neutropenias 12, occurred in two cases, both from PMSP. One, in a patient with Diamond‐Blackfan Anemia (DBA), was fatal 13; the other, in a patient with superficial siderosis, resolved. There were no reports of rash or eosinophilia concomitant with agranulocytosis.…”

Section: Resultsmentioning

confidence: 99%

“…Nonetheless, the DBA cases require attention. While the incidence of deferiprone‐induced agranulocytosis cannot be calculated in the absence of a known denominator, seven reported DBA cases suggest that agranulocytosis is more frequent in DBA than in thalassemia, as well as more severe 13, 14 (three cases were fatal, and several were associated with significantly diminished other leukocyte and platelet counts). Based on these data, we suggest that deferiprone therapy should not be initiated in patients with DBA, unless there is no alternative.…”

Section: Discussionmentioning

confidence: 99%

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Deferiprone‐induced agranulocytosis: 20 years of clinical observations

Tricta¹,

Uetrecht

Galanello

et al. 2016

American J Hematol

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Use of the iron chelator deferiprone for treatment of iron overload in thalassemia patients is associated with concerns over agranulocytosis, which requires weekly absolute neutrophil counts (ANC). Here, we analyze all episodes of agranulocytosis (n = 161) and neutropenia (n = 250) during deferiprone use in clinical trials (CT) and postmarketing surveillance programs (PMSP). Rates of agranulocytosis and neutropenia in CT were 1.5% and 5.5%, respectively. Of the agranulocytosis cases, 61% occurred during the first 6 months of therapy and 78% during the first year. These events appeared to be independent of dose, and occurred three times more often in females than males. Their duration was not significantly shortened by use of G‐CSF. No patient with baseline neutropenia (n = 12) developed agranulocytosis during treatment, which raises questions about the validity of prior neutropenia as a contraindication to use. Only 1/7 novel neutropenia cases in CT progressed to agranulocytosis with continued treatment, indicating that neutropenia does not necessarily lead to agranulocytosis. The agranulocytosis fatality rate was 0% in CT and 15/143 (11%) in PMSP. Rechallenge with deferiprone produced agranulocytosis in 75% of patients in whom the event had already occurred, and in 10% with previous neutropenia. Weekly ANC monitoring allows early detection and interruption of therapy, but does not prevent agranulocytosis from occurring. Its relevance appears to decrease after the first year of therapy, when agranulocytosis occurs less often. Based upon analysis of data collected over the past 20 years, it appears that patient education may be the key to minimizing agranulocytosis‐associated risks during deferiprone therapy. Am. J. Hematol. 91:1026–1031, 2016. © 2016 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Deferiprone‐induced agranulocytosis: 20 years of clinical observations

Tricta¹,

Uetrecht

Galanello

et al. 2016

American J Hematol

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“…The first report of agranulocytosis with DFP was in an adult patient with Blackfan-Diamond anemia, 47 and the drug should be avoided in this condition. 48 There have been no unexpected side effects in chelating DBA patients with DFX, and it was effective at lowering LIC and serum ferritin, although less so than in myelodysplasia. 102 We recommend to try DFX in patients inadequately chelated on DFO or with hypersensitivity to it.…”

Section: Congenital Anemiasmentioning

confidence: 90%

How I treat transfusional iron overload

Hoffbrand

Taher

Cappellini

2012

Blood

179

150

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Patients with ␤-thalassemia major (TM) and other refractory anemias requiring regular blood transfusions accumulate iron that damages the liver, endocrine system, and most importantly the heart. The prognosis in TM has improved remarkably over the past 10 years. This improvement has resulted from the development of magnetic resonance imaging (MRI) techniques, especially T2*, to accurately measure cardiac and liver iron, and from the availability of 3 iron-chelating drugs. In this article we describe the use of MRI to determine which adult and pediatric patients need to begin iron chelation therapy and to monitor their progress. We summarize the properties of each of the 3 drugs, deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX), including their efficacy, patient acceptability, and side effects. We describe when to initiate or intensify therapy, switch to another drug, or use combined therapy. We also discuss the management of refractory anemias other than TM that may require multiple blood transfusions, including sickle cell anemia and myelodysplasia.

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“…60 Although no cases of agranulocytosis were reported in this specific study even after a median duration of 13 months, 60 there are documented agranulocytosis-associated deaths in pediatric patients. 61 Weekly assessment of white blood cell count is therefore required for patients receiving deferiprone therapy. While licensed in Europe and other regions for iron overload, deferiprone is not licensed in the US or Canada, and is available in these countries only under a compassionate-use program.…”

Section: Deferipronementioning

confidence: 99%

Iron Overload and Iron Chelation Therapy in Pediatric Patients

Vichinsky¹

2009

Oncology &Amp; Hematology Review (US)

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Iron overload is an unfortunate clinical consequence of repeated blood transfusions that can cause significant organ damage, morbidity, and mortality in the absence of proper treatment. Pediatric patients with transfusion-dependent pathologies face the additional risk of growth failure and poor sexual development owing to iron build-up in the anterior pituitary gland. Iron chelation therapy is necessary for the removal of excess iron, but treatment efficacy and success are highly dependent on patient compliance. Deferoxamine is a well-established but inconvenient therapy requiring parenteral administration over extended periods of time. Patient compliance can be improved with use of the oral iron chelators deferasirox and deferiprone. Long-term data have shown deferasirox to have a good safety and efficacy profile in pediatric patients. KeywordsIron overload, hemoglobinopathies, pediatric, iron chelator, compliance Disclosure: Elliott Vichinsky, MD, is an investigator for and has received honoraria from Novartis.

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Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia

Cited by 60 publications

References 22 publications

Deferiprone‐induced agranulocytosis: 20 years of clinical observations

Deferiprone‐induced agranulocytosis: 20 years of clinical observations

How I treat transfusional iron overload

Iron Overload and Iron Chelation Therapy in Pediatric Patients

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