粒细胞集落刺激因子预激下小剂量Ara-C和ACR治疗复发难治急性髓细胞性白血病及骨髓增生异常综合征

目的:观察并评价在粒细胞集落刺激因子(GCSF)预激下小剂量阿糖胞苷(AraC)联合阿克拉霉素(ACR)方案(以下称AGA方案)治疗复发和(或)难治急性髓细胞性白血病(AML)和骨髓增生异常综合征(MDS)患者有效性和不良反应,从细胞凋亡方面探讨治疗方案的可能机制。方法:对复发难治的18例AML及4例MDS患者行AGA方案治疗。化疗方案:AraC10mg/m2,第1～14天,1次/12h,皮下注射;ACR8mg·m-2·d-1,第1～8天,静脉滴注;GCSF200μg·m-2·d-1,第1～14天,皮下注射,每次先于皮下注射AraC前1h开始。结果:9/18(50%)例AML接受1个AGA治疗即获完全缓解(CR),中位数缓解期4个月,其中6/10(60%)例M2获CR,22例治疗病例均无治疗相关死亡。20例接受传统标准剂量化疗对照组7例获得CR,4例死于化疗相关毒性。体外研究证实AGA方案明显提高新鲜白血病细胞凋亡率。结论:AGA方案对正常造血抑制较轻,非血液学不良反应小,外周血白细胞和血小板恢复较常规化疗组明显缩短。适于不能耐受常规治疗的、骨髓呈低增生的复发难治或老年AML患者,该药物协同诱导凋亡可能是该方案的治疗机制之一。

Combination regimen of low dose aclarubincin and cytarabine with G-CSF priming (AGA) for treating patients with relapsed or/and refractory acute myeloid leukemia and myelodysplstic syndrome

Objective:The aim of the study was to evaluate the efficacy and toxicity of combination of Aclarubincin with cytarabine (Ara-C) after priming with G-CSF (AGA regimen) in 18 patients with refractory or relapsed acute myeloid leukemia (AML) and 4 patient with MDS, and investigate the possible mechanism of AGA regimen.Method:Low-dose cytarabine 10 mg/m(2)/bid on days 1~14, aclarubincin 8 mg/m(2)/d on days 1~8, with priming granulocyte colony-stimulating factor (G-CSF) 200 ug/m(2)/d from day 1~14.Result:Eighteen AML patients received one course AGA therapy, 9/18(50%) patients achieved CR with a median duration of 4 months. Among of them 6/10 (60%) AML-M2 patients achieved CR. 22 patients were not related death with this regimen. Another 20 patients received conventional chemotherapy as a control group, 7/20 (35%) patients received CR with disease free survival 3 months. 4/20 patients died of toxicity of chemotherapy. The AGA regimen could induce apoptosis of fresh acute myeloid leukemia cells in vitro.Conclusion:This result showed that myelosuppression and non-hematological toxicities were lower and white blood cell and platelet count recovered faster than conventional chemotherapy. The CAG regimen could provide an excellent alternative for patients who need intensity chemotherapy, but who can not tolerate. Apoptosis induction might be a possible mechanism of AGA regimen