Timed sequential chemotherapy with concomitant granulocyte colony-stimulating factor for high-risk acute myelogenous...

The timed-sequential chemotherapy regimen consisting of etoposide, mitoxantrone and cytarabine (EMA) is an effective therapy for relapsed or refractory acute myelogenous leukemia (AML). We postulated that granulocyte colony-stimulating factor (G-CSF) might enhance the cytotoxicity of EMA by increasing the proportion of leukemic blasts in S-phase. We added G-CSF to EMA (EMA-G) for therapy of advanced high-risk AML patients.

High-risk AML was defined as refractory, relapsed or secondary to either an antecedent hematologic disorder or exposure to cytotoxic agents. The patients were treated with one course of EMA-G consisting of mitoxantrone and cytarabine on days 1-3, and etoposide and cytarabine on days 8-10. G-CSF was started on day 4 and continued until absolute neutrophil count recovered.

Thirty patients were enrolled. The median age was 51 years (range, 25-75). Seventeen (61%) patients had unfavorable cytogenetic karyotypes. Twenty (69%) patients had secondary AML. Ten (34%) had relapsed disease. Four (14%) had refractory AML. Three (10%) patients died from febrile neutropenia and sepsis. Major non-hematologic toxicity included hyperbilirubimenia, renal insufficiency, mucositis, diarrhea, nausea and vomiting, skin rash. A complete remission was achieved in 13 (46%) patients. Median overall survival was 9 months (range, 0.5-66). Median relapse-free survival (RFS) for those who had a CR was 3 months (range, 0.5-63) with RFS censored at the time of allogeneic bone marrow transplantation or peripheral stem cell transplantation for 6 of the patients.

EMA-G is a safe and efficacious option for induction chemotherapy in advanced, high-risk AML patients. The activity of EMA may be increased if applied in patients with less advanced disease.