CAG预激方案治疗急性髓细胞性白血病疗效分析

Effect of CAG induction therapy in patients with acute myeloid leukemia.

目的观察粒细胞-集落刺激因子（G-CSr）与小剂量AA方案组合（CAG方案），对急性髓细胞性白血病（AML）患者完全缓解率（CR）及总体生存（OS）、无病生存（DFS）时间的影响，并试图通过预后因素分析，确定CAG方案的最佳适合人群。方法21例AML患者采用CAG预激方案治疗，即阿糖胞苷（Ara—C）10ms／m2，皮下注射，每12小时1次，第1～14天。阿克拉霉素（ACR）5～7ms／m2，静脉注射，每天1次，第1～8天。G-CSF200斗吕／m2，皮下注射，每天1次，在Ara-C之前12h给予。结果CAG方案在21例AML患者中总CR率66．7％（14／21），60岁以上患者CR率87．5％（7／8），难治复发患者CR率60．0％（9／15），骨髓增生异常综合征（MDS）转化的AML患者CR率83．3％（5／6）。骨髓增生极度活跃与低下至明显活跃患者CR率分别为33．3％（3／9）、91．7％（11／12），差异有统计学意义（P=0．009）。21例AML患者中位总体生存时间为450d，2年生存率为30．6％，中位无病生存时间为165d。难治或复发患者中位总体生存时间为435d。高危核型与标危、良好核型患者中位总体生存时间分别为140d、620d（P=0．001）。骨髓增生极度活跃与低下至明显活跃患者中位总体生存时间分别为321d、620d（P=0．05）。21例患者中性粒细胞（ANC）〈1．0×109／L的中位时间8d，持续发热中位时间3．5d，按WHO的毒性标准〉2级的感染发生率为42．9％，无早期死亡病例。结论CAG预激方案可能提高难治复发AML、老年AML及继发于MDS的AML的CR率，延长难治复发患者的中位总体生存时间。发病时骨髓增生极度活跃患者及具有预后不良核型患者不能从CAG方案获益，应尝试其他方案治疗。CAG方案缩短粒细胞缺乏时间，严重感染发生率低，对于不耐受传统强烈化疗的患者值得考虑应用。

Objective To assess the effect of low-dose cytarabine and aclarubicin in combination with gran- ulocyte colony-stimulating factor （G-CSF） protocol （CAG） in patients with acute myeloid leukemia （AML） ,and to understand the potential factors affecting the outcome of CAG induction therapy, therefore to find the optimum patients for CAG therapy. Methods Twenty-one AML patients were enrolled in the current study. All patients were treated with CAG regimen including cytarabine （ 10 mg/m2, subcutaneously, every 12 h, days 1 - 14）, lacinomycin （5 -7 mg/m2 ,intravenously,every day, days 1 -8） ,and G-CSF （200 μg/m2 ,subcutaneously, every day,12 h be- fore Ara-C was given） priming. Results The overall complete remission （CR） rate of the 21 AML patients was 66.7% （ 14/21 ）. The CR rates was 87.5% （7/8） in patients older than 60 yrs,60.0% （9/15） in the refractory or relapsed patients,83.3% （5/6） in the MDS transformed AML patients. The CR rates for patients with hyperprolif- erative BM and median to poor proliferative BM were 33.3% and 91.7% , respectively（P = 0.009）. The median o- verall survival （OS） time of the 21 AML patients was 450 days. Two-year survival rate estimated by Kaplan-Meier Method was 30.6%. The overall median disease free survival （DFS） was 165 days. The median OS time for those refractory or relapsed was 435 days. The median OS time for those with poor cytogenetic state or standard or good cytogenetic state was 140 days and 620 days, respectively （P = 0. 001 ）. The median OS time for patients with hyperproliferative BM and median to poor proliferative BM was 321 days and 620 days, respectively （ P = 0.05 ）. The median recovery time of granulocytes above 1.0 × 109/L was 8 days. The median duration of fever was 3.5 days. The rate of infections exceeding WHO grade 11 was 42.9%. No early death occurred. Conclusions The CAG induction therapy may have a higher CR rate in patients with refractory or relapsed AML, elderly AML and secondary AML from MDS transformation, and extend the median overall survival time in refractory or relapsed patients. CAG therapy can not improve the outcome of patients whose BM was in high grade proliferation state or whose cytogenetic state was poor. CAG therapy can shorten the duration of agranulocytosis and decrease the incidence of serious infection. Therefore, CAG therapy is worth recommending to patients who can not endure the routine intensive chemotherapy.