CLAT联合微移植治疗难治性急性髓系白血病疗效观察
CLAT in Combination with HLA-mismatched Peripheral Blood Stem-Cell Microtransplantation for the Treatment of Refractory AML
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摘要: 目的 探讨克拉屈滨联合阿糖胞苷和拓扑替康(CLAT)方案联合供者粒细胞集落刺激因子动员的外周血单个核细胞(微移植,G-PBSC)治疗难治性急性髓系白血病(acute myeloid leukemia,AML)的有效性及安全性。 方法 广东省人民医院血液科2015年4月至2018年11月接受CLAT方案联合供者G-PBSC治疗难治性AML患者。CLAT方案:克拉屈滨5 mg/m2/d,静脉滴注,d1~d5;阿糖胞苷1 mg/m2/d,静脉滴注,d1~d5;拓扑替康1.25 mg/m2/d,口服,d1~d5;粒细胞集落刺激因子300μg/d,d6至中性粒细胞计数>1.0×109/L。目标剂量为单个核细胞2.0×108/kg或CD3+细胞1.0×108/kg。 结果 9例患者中位年龄34岁(范围:20~44岁);男性7例,女性2例,5例为原发难治性AML患者,4例为继发难治性AML患者。第一疗程疗4例(44.4%)患者获得完全缓解,3例(33.3%)患者获得部分缓解,总反应率为77.8%,累计完全缓解率为55.6%。9例患者均于微移植治疗后出现Ⅳ度骨髓抑制,中性粒细胞计数<0.5×109/L持续中位时间为14(7~21)天,血小板计数<20×109/L持续中位时间为8(0~19)天。 结论 CLAT方案联合供者粒细胞集落刺激因子动员后的外周血造血干细胞治疗难治性AML反应率高,不良反应可控。Abstract: Objective To investigate the efficacy and safety of cladribine combined with cytarabine and topotecan (CLAT) regimen combined with granulocyte colony-stimulating factor(G-CSF)-mobilized donor peripheral blood stem cell(G-PBSC) in the treatment of refractory acute myeloid leukemia (AML). Methods We analyzed refractory AML patients receiving programmed infusions of G-PBSC after the CLAT regimen of chemotherapy treatment. A total of 9 patients with refractory AML (median age 34 years, range 20 to 44 years, male n=7, female n=2) were treated with CLAT regimen which consisted of cladribine 5 mg/m2/d intravenously for 5 consecutive days (day 1~5) and topotecan 1.25 mg/m2/d in oral for 5 days(day 1~5) for priming combined with cytarabine of 1.5 g/m2/d q12h intravenously for 5 days (day 1~5). G-CSF of 300 μg/day subcutaneous injection on day 6 until neutrophil granulocyte count was ≥1.0×109/L. Donor stem cells were transfused into the patient at CD3+ cell 1.0×108/kg. Results Nine patients underwent at least one cycle of microtransplantation. After the first cycle, four patients (44.4%) achieved a complete remission (CR) and 3 patients (33.3%) achieved partial remission (PR), the overall response rate was 77.8%. Five patients had a CR rate of 55.6% after the second cycle. The median recovery time for neutrophils and platelets was 14(7~21) days and 8(0~19) days. Conclusion CLAT regimen in combination with microtransplantation was well tolerated and showed a promising clinic efficacy in patients with refractory AML.