Abstract
The development of more effective therapy for patients with refractory or relapsed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS) is a major concern in hematology. We previously reported a preliminary data that combination chemotherapy with topotecan, idarubicin, and intermediate dose cytarabine had a significant anti-leukemia activity and acceptable range of toxicity for the high-risk AML/MDS patients. In this study, we demonstrate an extended data for investigating larger number of patients with long-term follow-up of five years. The forty-seven patients were enrolled: 10 with primary refractory AML, 16 with AML in first relapse, 9 with AML in second relapse, and 12 with MDS-RAEB/RAEBT. Patients received as salvage therapy a single course of idarubicin 12 mg/m(2) IV bolus on days 1–3, cytarabine 1 g/m(2) over two hours q 12 hr on days 1–5, and topotecan 1.25 mg/m(2) over 24 hr on days 1–5. Median age of patients was 47 years (range 17–69 years). Patients with AML were categorized to high-risk (n=21), intermediate-risk (n=11), and low-risk (n=3) cyrogenetic group. All patients were evaluable for response: 23 (48.9%) achieved complete remission, 18 with AML (51.4%) and 5 with MDS (41.7%), respectively. The median remission duration and survival of patients with AML were 7 and 13 months, respectively. Median remission duration and survival of MDS patients was 10 and 15 months, respectively. Severe myelosuppression was observed in all patients, resulting in the fever or documented infections in 85.1% of patients. Median time to recovery of neutrophils > or =0.5 x 10(9)/l was 23 days (11–37 days) and for platelets > 20 x 10(9)/l 37 days (11–63 days). Reversible grade 3–4 toxicities included diarrhea (3 patients) and mucositis (13 patients). The relapsed AML patients (n=16) were grouped into four categories to stratify the probability of achieving complete remission (CR): group 1, first CR duration > 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 years and receiving S1; and group 4, first CR duration 0–1 years and receiving S2, S3, or S4 after failing S1. The response rate of group 4 (33.3%) was significantly lower than that of other groups (P < 0.05). We conclude that combination chemotherapy with topotecan, idarubicin, and intermediate dose cytarabine is an effective salvage chemotherapy for high risk AML/MDS patients, and the first CR duration is a significant predictor for response.
A Study of Human Leukocyte Antigen Mismatched Cellular Therapy (Stem Cell Microtransplantation) in High-Risk Myelodysplastic Syndrome or Transformed Acute Myelogenous Leukemia