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

BACKGROUND: 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. PURPOSE: To document real-life management strategies and outcomes for patients who experience neutropenia. METHODS: 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. RESULTS: 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. CONCLUSION: 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.