Dr. Sujit Sheth, Chief of the Division of Pediatric Hematology/Oncology at Weill Cornell Medicine and an attending pediatrician at New York Presbyterian Hospital, in New York City discusses his recently published work in Blood Advances titled “Rates of severe neutropenia and infection risk in patients treated with deferiprone: 28 years of data.”
My name is Dr. Sujit Sheth, and I am the Chief of the Division of Pediatric Hematology/Oncology at Weill Cornell Medicine and an attending pediatrician at New York Presbyterian Hospital, in New York City.
Along with my co-authors, it’s my pleasure to introduce you to our recently published work in Blood Advances titled “Rates of severe neutropenia and infection risk in patients treated with deferiprone: 28 years of data”.
Idiosyncratic drug-induced neutropenia or IDIN can occur with the use of many medications. Patients who develop severe IDIN have an absolute neutrophil count, or ANC, of less than 500/µL. Throughout the video, I will refer to severe IDIN as severe neutropenia. With the decline in neutrophils, these individuals are at risk of serious and sometimes fatal infections.
Deferiprone is an oral iron chelator indicated for transfusional iron overload in adult and pediatric patients with thalassemia, sickle cell disease, or other anemias. Treatment with deferiprone is associated with transient episodes of neutropenia of variable severity and predictability. Prior to this study, the risk of infection in patients who experience deferiprone-associated severe neutropenia, was not well studied. Our aim was to determine the risk of serious infection associated with severe neutropenia, stratified by ANC levels in patients taking deferiprone.
In this analysis, we used a large data set and extracted events of severe neutropenia and then we identified risk of serious infections that occurred within 2 weeks of those events. We used two data sets: company sponsored trials of deferiprone and the postmarketing surveillance program. Newly published guidelines by the EHA/INNOCHRON suggest that severe chronic neutropenias with ANC below 200/µL may be termed ‘agranulocytosis’ and they are associated with a high risk of severe, life-threatening infections. Therefore, in our analysis, we looked at serious infections associated with severe neutropenia within 3 discrete ANC groups. Group 1 with ANC between 200/µL and 500/µL; Group 2 with ANC between 100/µL and 199/µL, and Group 3 with ANC less than 100/µL.
In 15 company sponsored trials, we identified a total of 22 events of severe neutropenia. 9 events were within Group 1, 3 events were within Group 2, and 10 events were within Group 3. Interestingly, none of the events of severe neutropenia in Groups 1 and 2 were associated with serious infections. Of the 10 events in Group 3, 3 were associated with serious infections. There was also 1 death in Group 3. The death was due to hospital acquired pneumonia and multisystem organ failure following Pseudomonas sepsis associated with deferiprone-induced severe neutropenia.
From the postmarketing surveillance program, a total of 238 events of severe neutropenia were reported by clinicians, patients, or caregivers. Of those, 176 events had at least 1 ANC value reported. These events were then analyzed. Of these 176 events, 65 were in group 1, 20 in group 2 and 91 in group 3. There were 5 serious infections in group 1 or 7.7%, 2 in group 2 or 10%, and 12 in group 3 or 13.2%, showing a trend of increasing risk with lower ANC values. The mortality trend was similar, with 4.6% in group 1, 5% in group 2 and 8.8% in group 3. More details on all of the infectious events in this study can be found in the manuscript.
Based on our findings from 15 company sponsored trials of deferiprone and over 20 years of real-world data, we found that the lowest ANC levels below 200/µL or below 100/µL were associated with a higher risk of infections and mortality compared with the ANCs between 200/µL and 500/µL. This is also consistent with the European guidelines on neutropenia, which I mentioned previously.
In conclusion, our analysis has demonstrated that lower ANC thresholds of 200/µL or 100/µL may be more clinically relevant in the deferiprone treatment landscape and may be used to define agranulocytosis, somewhat reassuring both clinicians and patients. However, a proactive approach to monitoring ANC levels, and detecting early signs of infection is recommended for all patients regardless of the severity of neutropenia.
Reference
- Badawy SM, Palmblad J, Tricta F, et al. Rates of severe neutropenia and infection risk in patients treated with deferiprone: 28 years of data. Blood Advances. 2024;8(21):5641-5649. doi:10.1182/bloodadvances.2023012316
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