国产去甲氧柔红霉素治疗急性白血病56例安全性和有效性研究

The safety and efficiency of China made 4-demethoxydaunrubicin in the treatment of acute leukemia

目的评价国产去甲氧柔红霉素(艾诺宁)治疗急性白血病的安全性和有效性。方法采用前瞻性单中心研究,入组北京大学人民医院血液病研究所急性白血病患者56例。其中男30例,女26例;中位年龄34岁(14～62岁)。急性髓性白血病47例,急性淋巴细胞白血病9例;初诊病例35例,难治复发11例,缓解后巩固病例10例。急性髓性白血病采用IA方案化疗,急性淋巴细胞白血病采用COIP方案化疗,治疗前后检查血常规、肝功能、肾功能等,利用四色流式细胞术检测骨髓白血病细胞负荷,利用实时定量PCR检测白血病融合基因和泛肿瘤基因WT1。结果无国产去甲氧柔红霉素直接相关的死亡病例发生。患者均出现白细胞(WBC)3～4级毒性,WBC下降最低点时的中位值为0.64(0.1～1.8)×109/L,中位时间为13d(5～23d),造血恢复时WBC>109/L的中位时间为18d(3.3～42d)(12例WBC一直>1.0×109/L)。88%患者出现红细胞3～4级毒性,输红细胞悬液的中位数为4U(0～15U)。94%患者出现血小板(PLT)4级毒性,PLT>20×109/L的中位时间为19d(11～35d),需要输注PLT的中位数为5U(0～32U)。初治和难治复发患者的完全缓解率71.4%,有效率78.6%。完全缓解时白血病负荷下降倍数变化差异较大,可以达到11～1066倍(四色流式细胞术)和0.6～162.1倍(实时定量PCR)。结论国产去甲氧柔红霉素是治疗急性白血病的一种安全、有效的药物。国产去甲氧柔红霉素在降低白血病负荷方面因白血病类型不同而表现出较大的个体差异性。

Objective To evaluate the safety and efficacy of 4-demethoxydaunrubicin （IDA） made by China. Methods A prospective single-center clinical trial was carried out and 56 patients with acute leukemia including 47 acute myeloid leukemia patients and 9 acute lymphoblastic leukemia patients were enrolled. There were 35 newly diagnosed, 11 relapsed or refractory leukemia and 10 post-remission patients. IDA and cytarabine regimen was underwent in acute myeloid leukemia,while COIP regimen in acute lymphoblastic leukemia. 4 color-flow cytometry and real-time quantitative PCR were used to detect leukemia burden. Results The most common side effect was marrow suppression. The median of WBC was 0.64 × 10^9/L（ range 0. 1 - 1.8 ） at the median time of 13 days（ range 5 - 23 days）. The median time of WBC above 1.0 × 10^9/L and platelet above 20 × 10^9/L were 18 days and 19 days, respectively. The complete remission rate was 71.4% and overall response rate was 78.6% after induction therapy. The reduction folds of leukemia burden at the time of remission varied individually, 11 - 1066 by flow cytometry and 0. 6 - 162. 1 by real-time quantitative PCR. Conclusion IDA made by China is well safety and comparable efficacy. Leukemia burden may vary individually though in complete remission after IDA-based induction treatment.