高三尖杉酯碱、阿糖胞苷、去甲氧柔红霉素联合诱导治疗初治急性髓系白血病临床研究

本研究探讨高三尖杉酯碱(homoharringtonine)、阿糖胞苷(Ara-C)、去甲氧柔红霉素(idambin)组成的联合化疗方案(HAI)治疗初治急性髓系白血病(AML)(除外急性早幼粒细胞白血病)的疗效和安全性.31例初治AML患者接受HAI诱导化疗,统计1个疗程的缓解率、长期生存率及无复发生存率,比较WHO亚型、遗传学及初始白细胞计数等不同预后分组患者疗效,按照WHO抗癌药物不良反应评估标准进行安全性评价.结果表明,26例患者1个疗程后获完全缓解(CR),CR率为84％.染色体核型预后良好组(n=10)、预后中等组(n=16)、预后不良组(n=5)患者1个疗程的CR率分别为90％、88％、60％,组间差异无统计学意义(p=0.28).7例高白细胞数(白细胞计数≥100×109/L)患者均获CR,24例非高白细胞数组患者19例获CR.中位随访期15(2 -56)个月,全部患者3年累积生存率44％.26例CR患者3年累积生存率52％,3年无复发生存率为51％.所有31例患者均完成HAI诱导化疗,无化疗相关死亡病例.在诱导治疗期间所有患者均发生严重骨髓抑制,中性粒细胞绝对值＜0.2×109/L持续的中位时间为16(6 -24)天.31例患者均发生Ⅲ-Ⅳ级严重感染,抑制期中位发热持续时间为6(1 -36)天.败血症发生率为19.4％ (6/31);侵袭性真菌病发生率45.2％( 14/31),Ⅲ-Ⅳ级非血液学毒性反应以发热(非感染性)、谷丙转氨酶升高、腹泻、胆红素升高、口腔炎等最为常见,发生率分别为6.5％、6.5％、3.2％、3.2％、3.2％.结论:HAI方案治疗初治AML疗效肯定,特别是1个疗程的缓解率明显高于DA标准诱导方案.HAI方案安全性较好,除非发生严重感染.

Clinical study on combination of homoharringtonine, Ara-C and idarubicin induction for treatment of newly diagnosed acute myeloid leukemia patients

The purpose of this study was to assess the efficacy and toxicity of HAI regimen（（homoharringtonine 2.5 mg/（m2·d）,days 1-7;cytarabine 150 mg/（m2·d）,days 1-7;idarubicin 9 mg/（m2·d）,days 1-7）） for induction treatment of newly diagnosed acute myeloid leukemia（AML）（except acute promyelocytic leukemia）.31 patients with newly diagnosed AML,aged 39（14-58） years,were enrolled in this clinical study.The complete remission（CR） rate,especially after one course,the overall survival（OS） rate and relapse free survival（RFS） rate were estimated.The outcomes were compared between different prognostic groups according to World Health Organization（WHO） classification,genetics and initial WBC count.Safety was evaluated using standard WHO criteria.The results showed that 26 patients（84%） achieved CR after 1 course of induction.The CR rate for the patients with favorable,intermediate and unfavorable cytogenetics was 90%,88% and 60% respectively.All 7 patients with a high initial WBC count（≥100×109/L） obtained CR,while 19 out of 24 without a high initial WBC count obtained CR.With a median follow-up of 15（range 2-56） months,the estimated 3-year OS rate for all patients and the patients with CR was 44% and 52% respectively.The 3-year RFS rate was 51%.The patients receiving induction chemotherapy died of the chemotherapy.Profound myelosuppression was seen in all patients after the HAI induction with the medianduration of neutropenia（ANC 0.2 × 109 /L） of 16（6-24） days.As the most common toxicity,severe infections（grade Ⅲ-Ⅳ） involved in all the patients and the duration of febris was 6（1-36） days.The incidence of septemiaand invasive fungus infection were 19.4% and 45.2% respecticely.The incidence of non-infection fever,increasedglutamic-pyruvic transaminase（GPT）,diarrhea,increased bilirubin and oral cavity mucositis were 6.5%,6.5%,3.2%,3.2%,3.2% respectively,as the more frequent severe non-hematological toxicities.It is concluded that HAIregimen is a high efficient induction schedule for the newly diagnosed AML,and achive the higher CR rate after onecourse than DNR/Ara-C standard induction regimen.Side effects are acceptable,except severe infection.