Secondary hematologic malignancies associated with temozolomide (TMZ) in patients with glioma.

2046 Background: Temozolomide (TMZ) is a widely used alkylating agent in the treatment of gliomas. Although reports of treatment-related myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) associated with TMZ are accumulating, it remains unclear whether TMZ has the same leukemogenic potential as other alkylating agents. Methods: A single institution retrospective analysis was made using a database of 359 glioma patients treated with either nimustine (ACNU)-based, TMZ-based, or combination therapy and followed for a minimum of 2 months between January 1990 and December 2009 at the National Cancer Center Hospital in Japan. The objectives of this study were to characterize secondary hematological malignancies associated with TMZ and to estimate the rate of TMZ-related MDS/AML and ALL by comparing ACNU-based therapy. Results: Of the 359 patients, 225 patients received the therapy with ACNU alone or ACNU plus other chemotherapeutic drugs (ACNU-based group, median follow-up period: 31.4 months), 63 patients received ACNU-based therapy followed by TMZ therapy (ACNU/TMZ group, median follow-up period: 19.1 months), and 71 patients received the therapy with TMZ alone or TMZ plus other chemotherapeutic drugs (TMZ-based group, median follow-up period: 16.9 months). Three patients in ACNU-based group developed MDS/AMLs (1.33%, mean person year of MDS/AML: 6.4 years), two patients in ACNU/TMZ group developed MDS/AMLs (3.17%, mean person year of MDS/AML: 2.4 years), and one patient in TMZ-based group developed ALL (1.41%, mean person year of ALL: 1.1 years). Conclusions: Although retrospective analysis, relatively short follow-up period and small sample size in this study limit the strength of our conclusions, TMZ may increase the incidence of secondary hematologic malignancies and shorten their latency in combination with other chemotherapeutic agents. It is noteworthy that ALL occurs only in TMZ-based group with a relatively short latency in this series. No significant financial relationships to disclose.