Background. Higher-risk myelodysplastic syndrome (MDS) is often treated with intensive chemotherapy regimens used for acute myelogenous leukemia (AML). Patients with MDS are often older and may have contraindications to anthracycline-based regimens. Topotecan-cytarabine regimens had shown encouraging results in higher-risk MDS.

Study aims. To analyze the long-term results with topotecan-cytarabine versus other intensive chemotherapy regimens in higher-risk MDS.

Study Groups and Methods. 510 patients with higher-risk MDS (marrow blasts ≥ 10%) treated with intensive chemotherapy were reviewed. Median age was 63 years; 82% had intermediate 2 or high risk MDS; 52% had secondary MDS; 40% had chromosome 5 or 7 abnormalities. Therapy was: topotecan-cytarabine in 77; idarubicin-cytarabine regimens in 270; topotecan-cytarabine and cyclophosphamide in 67; fludarabine-cytarabine in 96. Univariate and multivariate analyses were conducted to evaluate the independent associations of different variables, and most importantly the treatment regimen, with complete response, induction, mortality, and survival.

Results. The overall CR rate was 55%, induction mortality 20%, and 5-year survival rate 8%. The 5-year survival rate was 11% for patients younger than 65 years old, and 17% for patients with a normal karyotype. Among 82 patients younger than 65 years with a normal karyotype, the CR rate was 67%, 5-year survival rate 27%, and 5-year CR duration rate 33%. Topotecan-cytarabine regimens were equivalent to idarubicin-cytarabine regimens in relation to CR rates and survival rates, but were associated with a lower induction mortality. Multivariate analysis confirmed that treatment regimens were not associated with independent significant differences in CR rates or survival. However, topotecan-cytarabine regimens were still selected to be associated with lower induction mortality rates.

Conclusions. Topotecan-cytarabine regimens are equally effective to other AML regimens in higher-risk MDS and may be less toxic. Topotecan-cytarabine should be considered as a reasonable alternative to idarubicin-cytarabine in higher-risk MDS, particularly in older patients with contraindications to anthracyclines.