IA联合小剂量HA+G-CSF方案序贯治疗原发初治急性髓系白血病的临床研究

 【摘要】　目的　观察IA方案去甲氧柔红霉素（IDA）+阿糖胞苷（Ara-C）]联合小剂量HA +粒细胞集落刺激因子（G-CSF）方案 高三尖杉酯碱（HHT）+Ara-C+G-CSF]序贯诱导治疗原发初治急性髓系白血病（AML）的疗效和安全性。方法　IA方案化疗后3 d复查骨髓，骨髓增生程度为活跃或者减低，原始细胞比例≥30 %的患者57例进入开放性非随机临床对照研究。第2个疗程化疗方案采用小剂量HA＋G-CSF方案的32例患者为研究组；仍为IA方案的25例患者为对照组。治疗过程中，观察患者临床表现、血常规、血生化和骨髓细胞学检查等指标。结果　研究组完全缓解（CR）21例（65.6 %），部分缓解（PR）4例（12.5 %），无早期死亡；总缓解率（ORR）为78.1 %。对照组CR 11例（44.0 %），PR 2例（8.0 %），早期死亡3例（12.0 %）；ORR为52.0 %。研究组ORR高于对照组，差异有统计学意义（χ2＝4.31，P＝0.038）。研究组中性粒细胞缺乏持续中位时间（9.5 d）短于对照组（28.0 d），差异有统计学意义（U＝32.5，P＜0.001），血小板计数从最低值恢复至50×109／L以上的中位时间（11 d）也短于对照组（19 d），差异有统计学意义（U＝193.0，P＝0.001）。研究组输注悬浮红细胞和血小板的中位数量（8 U，2个治疗量）少于对照组（16 U，6个治疗量），差异有统计学意义（U＝206.5，P＝0.002；U＝149.0，P＜0.001）。研究组应用静脉抗感染药物中位时间短于对照组（14 d比21 d），差异有统计学意义（U＝249.5，P＝0.015）。研究组严重内脏出血（消化道出血和脑出血）发生率3.1 %（1／32）]低于对照组24.0 %（6／25）]，差异有统计学意义（χ2＝3.90，P＝0.048）。结论　IA联合小剂量HA+G-CSF方案序贯诱导缓解治疗原发初治AML是安全有效的。

Clinical study on sequential treatment of newly diagnosed de novo acute myeloid leukemia patients with IA and low-dose HA combined with G-CSF regimens as remission induction therapy

Objective To evaluate the efficacy and safety of sequential treatment of newly diagnosed de novo acute myeloid leukemia （AML） patients with IA and low-dose HA combined with G-CSF regimens as remission induction therapy. Methods Fifty-seven patients with AML were enrolled, which marrow biopsy was hypoeellular or active proliferation on the third day from the end of the first course with IA regimen. 32 cases of them received the second course with low-dose HA combined with G-CSF regimen, compared with other 25 cases received the second course with another IA regimen. Clinical manifestations, blood count, blood biochemical parameters and bone marrow smears were measured during the courses. Results In study group, 21 of 32 cases reached CR, 4 PR, and 11 of 20 cases reached CR, 2 PR in control group. Overall remission rate （ORR） was higher in study group than that in control group （78.1% vs 52.0 %, P = 0.038）. Both median duration of agranulocytosis and median time for PLT to reach 50×10^9/L from the lowest were shorter in study group than those in control group （9.5 d vs 28.0 d, U= 32.5, P〈 0.001; 11 d vs 19 d, U= 193.0, P= 0.001）. Component transfusion, not only RBC but PLT, decreased in study group, compared with control group （8 U vs 16 U, U = 206.5, P = 0.002; 20 U vs 60 U, U = 149, P 〈 0.001）. Median durable time of antibiotic intravenous injection was shorter in study group than that in control group （14 d vs 21 d, U = 249.5, P= 0.015）. Visceral hemorrhage rate reduced in study group, compared with control group （X2 = 3.90, P = 0.048）. Conclusion IA and low-dose HA combined with G-CSF regimens sequential treatment as remission induction therapy for newly diagnosed de novo AML patients is effective and well tolerated.