Temozolomide-induced aplastic anaemia: Case report and review of the literature

Abstract

IntroductionTemozolomide (TMZ) is an oral alkylating agent principally indicated for neurological malignancies including glioblastoma (GBM) and astrocytoma. Most common side effects are mild to moderate, and include fatigue, nausea, vomiting, thrombocytopenia and neutropenia. Severe or prolonged myelosuppression, causing delayed treatment or discontinuation, is uncommon. Major haematological adverse effects such as myelodysplastic syndrome or aplastic anaemia (AA) have rarely been reported.Case reportWe report a 68-year old female with GBM treated at a tertiary hospital with short-course radiotherapy and concurrent temozolomide following craniotomy. On treatment completion she was transferred to our hospital for rehabilitation. She was thrombocytopenic on admission. Platelets continued falling with significant pancytopenia developing over the next two weeks. Blood parameters and a markedly hypocellular bone marrow confirmed the diagnosis of very severe AA, probably due to TMZ.Management and outcomeTreatment consisted of repeated platelet transfusions, intravenous antibiotics, antiviral and antifungal prophylaxis, and G-CSF 300 mcg daily. Platelet and neutrophil counts had returned to normal at 38 days following the completion of TMZ treatment.DiscussionWhilst most cases of AA are idiopathic, a careful drug, occupational exposure and family history should be obtained, as acquired AA may result from viruses, chemical exposure, radiation and medications. Temozolomide-induced AA is well documented, though only 12 cases have been described in detail. Other potential causes were eliminated in our patient. Physicians should be aware of this rare and potentially fatal toxicity when prescribing. Frequent blood tests should be performed, during and following TMZ treatment, to enable early detection.