This retrospective cohort study defined neutropenia as an absolute neutrophil count (ANC) < 1,500 cells/μL and agranulocytosis as ANC < 500 cells/μL. Over the 10-year study period, nine patients developed neutropenia, including one case meeting criteria for agranulocytosis. The cumulative incidence across the cohort was 1.38%, with an incidence rate of 0.27 cases per 100 person-years (95% CI 0.14–0.53).
The analysis included 654 adult patients (age ≥ 18 years) with thalassemia who started deferiprone (DFP) at Siriraj Hospital, Thailand, between January 2010 and December 2020. The cohort contributed 3,289.4 person-years of follow-up. The median age was 37 years and 70.8% were female. Most patients had Hb E/β-thalassemia. The study used retrospective chart review to capture clinical characteristics, neutropenia events, management strategies, and outcomes. Incidence rates were calculated per 100 person-years. Exploratory univariate Firth's penalized logistic regression was used to evaluate potential predictors of neutropenia.
The median time to onset of neutropenia was 146 days after initiating DFP, and the highest incidence of events occurred within the first 6 months of therapy. Patients with mild to moderate neutropenia were asymptomatic at detection. The single agranulocytosis case progressed to severe infection and sepsis.
Among the nine neutropenia cases, one patient with agranulocytosis died from severe sepsis, representing a case fatality rate of 0.03 per 100 person-years (95% CI 0.004–0.22). All other patients with mild or moderate neutropenia recovered following discontinuation of DFP. The median time to resolution of neutropenia in those who recovered was 56 days. These findings indicate that while most DFP-associated neutropenias in this cohort were asymptomatic and reversible, agranulocytosis can have severe outcomes.
Lower baseline peripheral blood counts were associated with higher risk of developing neutropenia. Specifically, lower baseline white blood cell (WBC) count and absolute monocyte count correlated with increased risk in exploratory analysis. A baseline WBC count ≤ 5,100 cells/μL demonstrated the highest predictive performance (area under the curve 0.86) in this dataset. The authors emphasize that this estimate is derived from eight events, has been optimism-corrected, and should be considered exploratory rather than definitive.
Management in this real-world cohort primarily involved early recognition and discontinuation of DFP when neutropenia was detected. Patients with mild to moderate neutropenia recovered after stopping the drug. The single agranulocytosis case resulted in a fatal outcome despite management. Selected patients were later rechallenged with DFP and did not experience recurrence of neutropenia in those instances, suggesting that rechallenge may be feasible for carefully selected patients under close monitoring. The report does not provide detailed standardized protocols for rechallenge, antibiotic use, or hospitalization criteria beyond these outcomes.
In this large single-center, real-world cohort of adult patients with thalassemia, DFP-induced neutropenia was uncommon but clinically important. Events clustered early in treatment, mostly within the first 6 months. Baseline cytopenias, particularly lower WBC and monocyte counts, may help identify patients at increased risk, though predictive findings are exploratory and based on a small number of events. With appropriate baseline assessment, frequent monitoring during early treatment, prompt recognition, and individualized management including drug discontinuation, DFP remains a viable and effective oral iron chelation option for adults with thalassemia. The fatality from agranulocytosis underscores the need for vigilance.
The study was approved by the Siriraj Institutional Review Board of the Faculty of Medicine, Siriraj Hospital, Mahidol University (Certificate of Approval number: si 826/2564 [IRB4]). The authors declared no competing interests.
The source highlights that certain analyses—particularly the predictive performance of baseline WBC—are exploratory and based on a small number of events (eight events contributing to the estimate), which limits robustness. Detailed standardized management protocols and granular data on rechallenge procedures were not reported in the abstract.
Agranulocytosis; Deferiprone; Neutropenia; Thalassemia