2053 Background: Secondary acute myeloid leukemia (AML) is reported to occur in 3%-10% of patients treated with alkylating agents for Hodgkin's lymphoma, non-Hodgkin's lymphoma, ovarian cancer, breast cancer, and multiple myeloma. The incidence of secondary AML is greatest at 5–10 years after treatment, and AML often follows myelodysplastic syndrome (MDS). TMZ is a pro-drug of methyl-triazeno-imidazole-carboxamide (MTIC), an alkylating metabolite of dacarbazine. Chemotherapy induced aplastic anemia is usually dose-related versus an idiosyncratic mechanism. A small number of fatal cases of TMZ-induced aplastic anemia have been reported. The FDA, in a Drug Safety Newsletter, described 18 cases of aplastic anemia reported between 1999 and 2006. TMZ use in brain tumors and in melanoma is increasing, with little known on the incidence of severe hematologic adverse events. Methods: We searched the FDA MedWatch database for TMZ and obtained all entries submitted to the FDA from November 1, 1997 to September 3, 2008. We also obtained the number of aplastic anemia cases reported from Schering Plough's Global Pharmacovigilance department, as of December 13, 2007. Results: During this time period, 5,127 reports (on any side effect) on 3,490 patients were submitted to MedWatch. Among these patients, we identified 140 cases that we labeled as major hematologic adverse events: agranulocytosis (8 cases), aplasia (42), aplastic anemia (52), leukemia (26), MDS (6), and lymphoma (6). Gender was reported in 133 cases. Of these, 56 were male and 77 were female. The overall mean age in cases of major hematologic adverse events was 54 years. Schering Plough reports 25 cases of aplastic anemia and estimates the frequency to be 10.22 per 100,000 patients exposed to TMZ. Conclusions: TMZ's major hematologic adverse event profile seems to differ compared with other alkylating chemotherapy. Aplastic anemia is a significant concern with TMZ use and should be disclosed to patients. Risk of leukemia/MDS from our review may also be significant, but length of follow-up is insufficient and the real risk is likely still unknown. No significant financial relationships to disclose.