Idarubicin, cytarabine, and topotecan in patients with refractory or relapsed acute myelogenous leukemia and high-risk myelodysplastic syndrome

In an effort to develop more effective therapy for patients with refractory or relapsed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of a combination chemotherapy consisting of idarubicin, cytarabine, and topotecan. Twenty-seven patients were treated: four with primary refractory AML, nine with AML in first rel apse, four with AML in second relapse, and 10 with MDS-RAEB/RAEBT. Patients received as salvage therapy a single course of idarubicin 12 mg/ m(2) IV b olus on days 1-3, cytarabine 1 g/m(2) over two hours q 12 hr on days 1-5, a nd topotecan 1.25 mg/m(2) over 24 hr on days 1-5. Median age was 42 years ( range 17-65 years). All patients were evaluable for response: 14 (51.9%) ac hieved complete remission, 10 with AML (59%) and four with MDS (40%), respe ctively. Thirteen AML patients (excluding four relapsed after autologous st em cell transplantation) were grouped into four categories to stratify the probability of achieving complete remission (CR): group 1, first CR duratio n > or = 2 years and receiving first salvage treatment (S1); group 2, first CR duration 1-2 years and receiving S1; group 3, first CR duration 0-1 yea rs and receiving S11; and group 4, first CR duration 0-1 years and receivin g S2, S3, or S4 after failing S1. The response rate of each group was as fo llows: group 1, one of two (50%); group 2, one of one (100%); group 3, four of four (100%); group 4, two of six (33.3%). The median remission duration and survival of patients with AML were six and 12 months, respectively. Me dian duration of survival in 10 MDS patients was 15 months, and all four MD S patients achieving a CR maintained continuous CR with a median follow-up of I I months. Severe myelosuppression was observed in all patients, result ing in fever or documented infections in 89% of patients, Median time to re covery of neutrophils greater than or equal to0.5 x 10(9)/l was 22 days (11 -34) and for platelets > 20 x 10(9)/l 35 days (11-58). Reversible grade 3-4 toxicities included diarrhea (two patients) and mucositis (seven patients) . We conclude that combination chemotherapy with intermediate dose cytarabi ne, idarubicin, and topotecan has significant antileukemic activity and acc eptable toxicity in salvage AML and high-risk MDS. (C) 2001 Wiley-Liss, Inc .