We report the case of a 65 year old gentleman presenting for investigation of pancytopenia. His background history includes that of glioblastoma multiforme diagnosed in 2016 which was successfully resected and treated with combined chemoradiotherapy consisting of temozolomide.
Haematinic studies showed normal B12, folate and iron stores. There was no evidence of liver derangement. FBC done at the time of bone marrow biopsy showed Hb 98g/L, MCV 114fL, WCC 3.5x10^9/L, Neut 0.98x10E9/L, Plt 166x10E9/L. Blood film demonstrated hyposplenic changes but granulocytes did not appear overtly dysplastic.
Bone marrow biopsy showed dysplastic megakaryopoiesis and micromegakaryocytes and mild dyserythropoiesis without any significant dysgranulopoiesis. Blast accounted for 1% of cellularity. Karyotyping demonstrated 45, XY with monosomy 7. In the context of previous temolozomide use, the diagnosis of therapy related myeloid neoplasm (t-MN) was made.
Temozolomide is an oral non-classical alkylating agent used as adjuvant therapy for the treatment of glioblastoma multiforme. Studies have shown a benefit in overall survival in combination with radiotherapy and is now standard of care for high grade gliomas. Grade 3 or 4 haematological toxicity occurs in approximately 7% of patients with thrombocytopenia the most common reason for drug discontinuation.
Therapy related myeloid neoplasms (t-MN) due to alkylating agents often occur 5 to 10 years after completion of therapy. However, reports have shown temozolomide induced myelodysplastic syndrome appears to have a shorter latency period (range 8-36 months). Due to the poor prognosis of patients with glioblastoma, there is paucity of data on the long term effects of temozolomide. Nevertheless, clinicians should be aware of the potential risk of t-MN associated with temozolomide use.