The Experimental Research And Clinical Observation On The Treatment Of Refractory/relapse Acute Myeloid Leukemia With Topoisomerase Ⅰ Inhibitors Topotecan

ObjectiveRecently, results of phase I /II clinical trials have demonstrated that topoisomerase (Topo) I inhibitor Topotecan (TPT) and chemotherapy containing TPT are effective alternative for treatment of the patients with refractory or relapsed acute myeloid leukemia (AML). To further prove the pharmacologic mechanism of TPT, this study initially explored the effect of TPT on the inhibition of proliferation and proapoptotic activity of MUTZ-1 cells(MDS-RAEB transforming to AML cell line) in vitro, and the effect of cyclophosophamide (CTX) on the expression level of mRNA in MUTZ-1 cells. Meanwhile, the outcomes and side effects of cyclophoaphamide, cytarabine, topotecan (CAT) combination regimen for the treatment of refractory or relapsed AML were also observed. Methods1. The cytotoxic effect of TPT on MUTZ-1 cells was determined by MTT assay.2. TPT-induced apoptosis in MUTZ-1 cells was identified by electron microscopy, flow cytometry (FCM) analysis with AnnexinV-FITC staining and electrophoresis of DNA.3. The changes of cell cycle were observed by FCM with PI staining4. The effects of CTX on the expression level of Topo-I mRNA were determined by hemi-quantitative RT-PCR.5. Twenty-one patients with refractory or relapsed AML were administered CAT regimen. Remission rate, median survival were calculated and related prognostic factors were analyzed. The differences between CAT and non-CAT regimen in suppression of bone marrow and supportive treatment were compared.Results1. After incubation of MUTZ-1 cell with 5, 10, 20, 40, 80 and 160nmol/L TPT for 72h, the survival rates, compared with control (505.6±20.1)%, progressively reduced to (78.9±10.7)...