Albert K Park1,2, Anem Waheed2,3, Deborah A Forst2,4, Hanny Al-Samkari2,3. 1. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. 2. Harvard Medical School, Boston, Massachusetts, USA. 3. Division of Hematology Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA. 4. Division of Neuro-Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Temozolomide-induced aplastic anemia (TIAA) is a rare but highly challenging complication of temozolomide (TMZ) therapy. Evidence describing prognosis, clinical characteristics, and treatment of this entity is very limited. METHODS: We performed a multicenter, 22-year observational cohort study of patients with central nervous system (CNS) malignancies treated with temozolomide who developed TIAA, retrospectively analyzing prognosis, complications, and recovery. TIAA was defined using adapted evidence-based severe aplastic anemia criteria incorporating profound cytopenias and a minimum duration (4 weeks) without hematologic recovery. RESULTS: Of 3821 patients with CNS malignancies receiving TMZ, 34 patients (0.89%) met criteria for TIAA. Onset was rapid, with 29 patients (85.3%) developing TIAA before completing a second TMZ cycle. 23 patients (67.6%) ultimately achieved a hematologic recovery. Patients without recovery were more likely to develop febrile neutropenia (72.7% vs. 30.4%, P = .03), infectious complications (45.5% vs. 8.7%, P = .02), require hospitalization (81.8% vs. 43.5%, P = .04), and die (100.0% vs. 60.9%, P = .02). Median overall survival from TIAA diagnosis was 752 days in patients achieving a partial hematologic recovery versus 28 days in those who did not (P < .0001). 29 patients (85.3%) received one or more hematopoietic growth factors; hematologic recovery rates were higher in patients receiving thrombopoietin receptor agonists (81.8% vs. 60.9%) but were not higher in patients receiving granulocyte colony-stimulating factors. CONCLUSIONS: TIAA occurs in <1% of patients receiving TMZ for CNS malignancies, but is highly morbid when it occurs and frequently fatal in the one-third of patients not achieving hematologic recovery. Thrombopoietin receptor agonists may improve the likelihood of a hematologic recovery.
BACKGROUND: Temozolomide-induced aplastic anemia (TIAA) is a rare but highly challenging complication of temozolomide (TMZ) therapy. Evidence describing prognosis, clinical characteristics, and treatment of this entity is very limited. METHODS: We performed a multicenter, 22-year observational cohort study of patients with central nervous system (CNS) malignancies treated with temozolomide who developed TIAA, retrospectively analyzing prognosis, complications, and recovery. TIAA was defined using adapted evidence-based severe aplastic anemia criteria incorporating profound cytopenias and a minimum duration (4 weeks) without hematologic recovery. RESULTS: Of 3821 patients with CNS malignancies receiving TMZ, 34 patients (0.89%) met criteria for TIAA. Onset was rapid, with 29 patients (85.3%) developing TIAA before completing a second TMZ cycle. 23 patients (67.6%) ultimately achieved a hematologic recovery. Patients without recovery were more likely to develop febrile neutropenia (72.7% vs. 30.4%, P = .03), infectious complications (45.5% vs. 8.7%, P = .02), require hospitalization (81.8% vs. 43.5%, P = .04), and die (100.0% vs. 60.9%, P = .02). Median overall survival from TIAA diagnosis was 752 days in patients achieving a partial hematologic recovery versus 28 days in those who did not (P < .0001). 29 patients (85.3%) received one or more hematopoietic growth factors; hematologic recovery rates were higher in patients receiving thrombopoietin receptor agonists (81.8% vs. 60.9%) but were not higher in patients receiving granulocyte colony-stimulating factors. CONCLUSIONS: TIAA occurs in <1% of patients receiving TMZ for CNS malignancies, but is highly morbid when it occurs and frequently fatal in the one-third of patients not achieving hematologic recovery. Thrombopoietin receptor agonists may improve the likelihood of a hematologic recovery.
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