Homoharringtonine Based Triple-Drug Regimen as Induction Chemotherapy for De Novo Acute Myelogenous Leukemia.

HAA regimen, consisting of homoharringtonine (HHT), aclarubicin and cytarabine (Ara-C), is an efficacious chemotherapy regimen for induction treatment of acute myelogenous leukemia (AML). HHT, a plant alkaloid that is derived from a Chinese evergreen tree, has been shown to inhibit protein, DNA, and RNA synthesis by inhibition of chain initiation. HAA regimen consists of HHT administered at a dose of 4 mg/m²/day by continuous infusion over 4 hours or 2 mg/m² intramuscular injection twice daily on days 1–3, aclarubicin administered at a dose of 12 mg/m²/day by continuous infusion over 2 hours on days 1–7, and cytarabine (Ara-C) given at a dose of 75 mg/m² twice daily on days 1–7. Granulocyte colony-stimulating factor (Lenograstim) 5 μg/kg/day subcutaneously was started from the day neutrophil count <0.5×10⁹/l, and continued until the day neutrophil count >1.0×10⁹/l on 3 successive days. For patients with partial remission (PR) after the evaluation of the first course of the therapy, another same induction HAA regimen was administered. Between May 1999 and June 2006, 80 patients consisted of 31 male and 49 female patients were enrolled. All patients had newly diagnosed with de novo AML and had not received any induction treatments before. Out of them, 3 were M1, 44 M2, 2 M4, and 31 M5 according to FAB classification criteria. The median age was 36 (14–59) years. Of all the 76 patients with cytogenetic analysis available, 13 had favorable karyotype, 58 intermediate karyotype, and 5 unfavorable karyotype. In all, 68 (85%) patients achieved complete remission (CR), and the first single course of this induction regimen resulted in a CR rate of 75%. The CR rate of 100%, 88% and 20% were achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. We also found that patients with M5 achieved a CR rate of 74% (23/31), while patients with M1 or M2 94% (44/47). The toxicities associated with this regimen were no more than those expected with standard chemotherapy, and the most common non-hematological toxicity was infection. This study suggested that HAA regimen is a safe regimen and it is efficacious, well-tolerable induction therapy for newly diagnosed de novo AML, the use of G-CSF (Lenograstim) appears to be safe, with little risk of accelerating leukemic relapse. A high CR rate can be achieved with only one or two courses of this regimen. Besides, cytogenetics is an important prognostic factor.