Granulocyte Colony Stimulating Factor (G-CSF, filgrastim) is now widely used after chemotherapy which complicates hematological toxicity involving neutropenia. As prolonged neutropenia leads to neutropenic fever due to bacteremia or fungal infection, the use of G-CSF prevents severe infectious complication in various cancer patients.

In acute myeloid leukemia (AML), leukemic blasts have been expected to have G-CSF receptor which may be stimulated by G-CSF, and refractory patients were not treated with G-CSF in salvage chemotherapy in Catholic blood and marrow transplantation (BMT) Center for a long time. This strategy induced prolonged neutropenia and a lot of infectious complications some of which led to deaths.

Although there are some data which remind us G-CSF may proliferate leukemic blasts, the investigators also identified several reports which suggested that subgroup with G-CSF use showed acceptable CR rate and improved survival outcomes compared to a subgroup without G-CSF use.

Therefore investigators are now trying to identify the effects of G-CSF for refractory AML patients in salvage chemotherapy setting regarding the duration of neutropenia and admission, incidence of infectious complications and the duration of antibiotics application. Furthermore, overall response rate (CR+CRi) after salvage chemotherapy and survival outcomes will be calculated according to G-CSF use.

Also, investigators will detect G-CSF receptor using cluster of differentiation 114 (CD114), and analyze the clinical outcomes according to the subgroups with or without using G-CSF during neutropenic period.

Patients will be treated with mitoxantrone and etoposide and cytarabine. Patients will be randomly divided according to the usage of G-CSF.

Subgroup with G-CSF will be treated with G-CSF after 7~10 days post-chemotherapy, when blasts will disappear from peripheral blood.

Subgroup without G-CSF will be observed until 25~28 days post-chemotherapy. If blood counts are nor recovered, the investigators can perform bone marrow biopsy to identify the status of the bone marrow.

After then, G-CSF can be applied if blasts are not observed in both peripheral blood and bone marrow.

When absolute neutrophil counts are recovered and there are no evidence of infectious complications, patients will discharge safely from hospital.

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status 0~2
• AML with remission failure after standard chemotherapy
• Stable liver and renal function (=< Upper normal limit (UNL) x 2.5)
• Stable heart and lung function (Ejection Fraction (EF) > 45%, Forced expiratory volume at one second (FEV1) > 40%)

Exclusion Criteria:

• Acute promyelocytic leukemia
• Central nervous system (CNS) involvement
• Uncontrolled bleeding
• Uncontrolled infectious complication
• Pregnancy, Breast feeding
• Significant cardiovascular disease within 6 months
• Significant organ failure (> UNL x 2.5)