三氧化二砷联合FLAG方案治疗复发急性髓性白血病及对白血病干细胞的影响

探讨三氧化二砷（Arsenic Trioxide，AT）联合改良氟达拉滨+阿糖胞苷+粒系集落刺激因子（FLAG）方案治疗复发难治急性髓性白血病（AML）的疗效以及对白血病干细胞（leukemia stem cells，LSC）的作用。方法：10例难治和复发AML患者采用AT联合FLAG方案治疗，观察临床治疗效果，并检测治疗前后患者骨髓中LSC和P-gp阳性细胞数的变化。结果：10例患者经AT联合FLAG方案治疗，持续缓解时间平均8个月（4～12个月），完全缓解率（CR）3个月、6个月和12个月分别为80%、60%和25%。10例患者均出现了Ⅳ度骨髓抑制，但未出现其它严重不良反应，无1例在治疗过程中死亡。骨髓中P-gp+细胞由治疗前的（23.55±2.75）%降为治疗后的（11.67±3.50）%；骨髓中LSC（CD34+CD38-CD123+）的相对含量显著降低，治疗前和治疗后分别为（4.30±1.30）%和（2.60±0.70）%。结论：AT联合改良FLAG方案可有效诱导难治和复发急性髓性白血病患者缓解，并降低患者骨髓中白血病干细胞（LSC）和P-gp+细胞的数量。

Arsenic Trioxide Combined with a Modified Fludarabine and Cytarabine plus Granulocyte Regimen for Relapsed Acute Myeloid Leukemia and Its Curative Effects on Leukemia Stem Cells

Abstract Objective: To study the curative effects of arsenic trioxide (AT) combined with a modified fludarabine and cytarabine plus granulocyte regimen (FLAG schedule) on relapsed and refractory acute myeloid leukemia, as well as the therapeutic efficacy of the schedule for leukemia stem cells (LSC). Methods: Ten patients with relapsed acute myeloid leukemia who have been co-treated with AT-FLAG schedule were enrolled in the study to observe the curative effects of the treatment. The proportion of LSC- and P-glycoprotein ( P-gp )-positive cell population in the bone marrow was detected before and after the treatment. Results: After treatment with the combined therapeutic regimen, i.e., the AT-FLAG schedule, severe adverse effects and death were not observed during chemotherapy. The average time of complete continuous remission was 8 months (4-12 months), and complete remission ( CR ) at 3, 6, and 12 months after the treatment was 80%, 60%, and 25%, respectively. Grade IV myelosuppression occurred in all treated patients. The ratio of P-gp+ cells in the bone marrow decreased from ( 23.55% ± 2.75%) before the drug administration to (11.67% ± 3.50%) after the treatment, and the relative amounts of LSC ( CD34+CD38-CD123+ ) before and after the treatment was (4.30% ± 1.30%) and (2.60% ± 0.70%), respectively. Conclusion: The AT-FLAG combined chemotherapy efficiently induced CR of relapsed and refractory acute myeloid leukemia and decreases the LSC and P-gp+ cell content in the bone marrow of patients.