Abstract

<Background> The optimal strategy for management of the elderly patients with acute myeloid leukemia (AML) is still controversial with opinions frequently polarized between intensive chemotherapy and conservative therapy. We cannot often help hesitating to select intensive chemotherapy for some elderly patients due to poor performance status (PS) or some complications. So we have been employing continuous drip infusion of low dose cytarabine (Ara-C) and etoposide (VP-16) for 10 days (AV therapy) according to PS and some complications at the diagnosis for elderly patients with AML and obtained a constant effect. Experimental studies demonstrated that priming with granulocyte colony-stimulating factor (G-CSF) recruits leukemia cells into cell cycle, leading to greater sensitivity of leukemia cells against Ara-C. We aimed more improvement of efficacy by using G-CSF with AV therapy (AVG therapy).

<Patients> Eligibility for enrollment was limited to consecutive patients aged 60 and over with AML according to the WHO classification between 1998 and 2005 who hardly tolerable for intensive chemotherapy by reason of poor PS (0–3) or some non-hematological complications. Acute promyelocytic leukemia with t(15;17) and patients with greater than 10x109/L in the number of peripheral white cell counts were excluded.

<Treatment Design> This study was done prospectively. Patients with poor PS or some non-hematological complications were given continuous drip infusion of low dose Ara-C, 20mg /body and VP-16, 50mg/body, for 7 to 14 days. G-CSF (lenograstim) was administered simultaneously at the dose of 100 to 250μg/body by daily once. Bone marrow aspiration was examined at day 8 or 11 and chemotherapy was discontinued if less than 10x109/L in the number of nuclear cell counts of the marrow. If neutrophils in peripheral blood were more than 10x109/L, G-CSF was suspended.

<Results> The median age of enrolled 23 patients was 73-year-old. Fourteen patients had de novo AML not categorized, 9 patients had multilineage dysplasia by the WHO classification. Seventeen (73.9%) of 23 patients achieved CR. The 1-year over all survival rates (OS) and the 3-year OS were 77.8% and 19.4%, respectively. The 1-year disease free survival rates in CR patients were 32.1%. Mean duration of DFS was 11.9 months and average expectation of life in all patients was 22.5 months. Regimen related death during remission induction therapy was not observed. Febrile neutropenia with grade 3 was observed in 11 patients, but no other regimen related toxicities with grade 3 or 4 were observed. Increase of blasts in bone marrow during the course of chemotherapy was not observed.

<Conclusion> AVG therapy was at least an effective and well-tolerated regimen as induction therapy for elderly AML patients with poor PS or some non-hematological complications. It is necessary to investigate a controlled clinical trial for determination of a more precise induction therapy including AV, AVG and conventional intensive chemotherapy.

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