Homoharringtonine In Combination With Cytarabine and Etoposide For Induction Therapy In Patients With De Novo Acute Myelogenous Leukemia
Authors: He Jingsong , Li Li , Zhu Jingjing , Zhao Yi , Wu Wenjun , Zheng Yanlong , Zheng Gaofeng , Zheng Weiyan , Zhu Xiaoli , Huang He , Ye Xiujin 
Published: October 2019

Abstract
Homoharringtonine (HHT) is one of antineoplastic alkaloid extracted from Cephalotaxus of China. Its main function is to inhibit protein synthesis. Its cytotoxicity is cell cycle specificity, which mainly affects G1 and G2-cyle cells and can induce the apoptosis of acute myeloid leukemic cells and has no obvious cross resistance to the drugs like daunorubicin and cytarabine (Ara-C).
This research has made a preliminary assessment to the efficacy and safety of HAE regimen’s induction therapy to patients with de novo acute myeloid leukemia (AML). From March 2011 to June 2013, 35 patients with de novo AML have been enrolled, of which 18 are males and 17 females with median age as 42y (19∼60); there are three M0 and M1 cases respectively, thirteen M2 cases, six M4 cases and ten M5 cases. The myeloid leukemia cell is 71.5% (20.5%∼94%). According to the detection result of chromosome and gene mutation, the patients are divided into eight high-risk cases and 27 low-and-medium-risk cases. The chemotherapy program is HAE, HHT 2.5mg/m2/d, d1–7, Ara-C 100mg/m2/d, d1–7, Etoposide 60mg/m2/d, d1–7. If complete remission (CR) or CR with no recovery of hemogram (CRi) is obtained after one course of treatment, another one course of treatment will be given as consolidation therapy. If partial remission (PR) is obtained, another one course of treatment will be made and if CR or CRi is obtained then, another one course of treatment will be made for consolidation therapy, otherwise, exit the test.

Result
Curative effect of one course of treatment, 23 (65.7%) cases obtaining CR or CRi and 4 (11.4%) cases obtaining PR, of which 3 cases obtained CR or CRi after another one course of treatment. The total effective rate of 2 courses of treatment was 74.3% (26/35), 6 (17.1%) cases to which the treatment achieved no effect (including 1 case obtaining PR in the first course of treatment), 3 (8.6%) cases encountered earlier death. The time of median follow-up is 11.2m (1.1∼28.7m). In the 26 patients achieved CR or CRi, 4 cases encounter recurrent of disease (15.4%), with the median recurrence free survival (RFS) not met, and the 2-years estimated RFS was 73%. In the 35 patients, 5 (14.3%) cases died, including 3 cases of earlier death and 2 cases die of recurrence of disease, with the median overall survival (OS) not met, the 2-years estimated OS was 83%. In the 26 patients obtaining CR or CRi, the average RFS without recurrence of low-and-medium-risk and high-risk patients was 24.9 ± 2.0m and 14.5 ± 0.4m (p = 0.465) respectively, and in the 35 patients, the average OS of low-and-medium-risk and high-risk patients was 25.5 ± 1.8m and 11.6 ± 3.7m (p = 0.236) respectively. Non-hematologic adverse reaction of HAE program includes infection (88.6%, 31/35), diarrhea (11.4%, 4/35), pulmonary fungal infection (20.0%, 7/35) and atrial fibrillation (2.9%, 1/35), of which grade 3∼4 adverse reaction is infection (37.1%, 13/35).

Conclusion
HAE program is tolerable and effective program for first-line treatment of AML.

Disclosures:
No relevant conflicts of interest to declare.