Neutropenia in adult patients with thalassemia receiving deferiprone: a 10-year experience from a large thalassemia cohort

Abstract

Deferiprone (DFP) is an effective oral iron chelator widely used in adult patients with thalassemia, particularly for cardiac iron removal. However, DFP is associated with rare but potentially life-threatening hematological adverse effects, notably neutropenia and agranulocytosis. Real-world data on the incidence, timing, risk factors, and outcomes of DFP-induced neutropenia in adult patients with thalassemia are limited. To document real-life management strategies and outcomes for patients who experience neutropenia. We conducted a retrospective cohort study of adult (≥ 18 years) patients with thalassemia who initiated DFP therapy at Siriraj Hospital, Thailand, between January 2010 and December 2020. Neutropenia was defined as an absolute neutrophil count (ANC) < 1,500 cells/μL and agranulocytosis as ANC < 500 cells/μL. The incidence rates were calculated per 100 person-years. Clinical characteristics, management strategies, outcomes, and potential prognostic factors were analyzed using exploratory univariate Firth’s penalized logistic regression to identify the predictors of neutropenia. A total of 654 patients were included (median age 37 years; 70.8% female), predominantly with Hb E/β-thalassemia. Over 3,289.4 person-years of follow-up, nine patients developed neutropenia, including one case of agranulocytosis, yielding a cumulative incidence of 1.38% and an incidence rate of 0.27 cases per 100 person-years (95% CI 0.14–0.53). The median time to neutropenia onset was 146 d, with the highest incidence occurring within the first 6 months of therapy. One patient with agranulocytosis died from severe sepsis, corresponding to a case fatality rate of 0.03 per 100 person-years (95% CI 0.004–0.22). All patients with mild to moderate neutropenia were asymptomatic and recovered after DFP discontinuation, with a median time to resolution of 56 d. Lower baseline white blood cell (WBC) count and absolute monocyte count were associated with increased risk of neutropenia; a baseline WBC count ≤ 5,100 cells/μL demonstrated the highest predictive performance (AUC 0.86), although this estimate was derived from eight events, is optimism-corrected, and should be considered exploratory. The selected patients were rechallenged with DFP without any recurrence. In this large real-world cohort, DFP-induced neutropenia was uncommon but clinically significant, occurring predominantly within the first 6 months of therapy. Baseline cytopenia may help identify patients at a higher risk. With appropriate monitoring, early recognition, and individualized management, DFP remains a viable and effective iron chelation option for adult patients with thalassemia.