Qian Si-Xuan, Wu Han-Xin, Hong Ming, Lu Hua, Xu Wei, Li Jian-Yong
Department of Hematology, The First Affiliated Hospital, Nanjing Medical University, Jiangsu Province People Hospital, Nanjing 210029, Jiansu Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Dec;17(6):1577-81.
The objective of study was to primarily explore the efficacy of combination of high doses cytarabine, fludarabine and G-CSF (FLAG) as the consolidation therapy for patients with acute myeloid leukemia (AML), and to analyze the influence of FLAG on peripheral stem cell mobilization. 31 patients with AML in complete remission were divided into two groups based on induction regimens, e.g. IA group (idarubicin and cytarabine) and non-IA group. All patients were consolidated with FLAG regimen which including fludarabine 50 mg/d, days 1-5; Ara-C 2 g/(m(2).d), days 1-5; G-CSF 300 microg/d. Time of its use sustained from day 0 until absolute neutrophil count > 1.0 x 10(9)/L. 17 patients received 2 or 3 courses of FLAG regimen, and 14 patients took 1 course. 9 patients received 2 courses of FLAG regimen as consolidation therapy, and then peripheral stem cells were collected from them. The results showed that sufficient peripheral stem cells were obtained in 7 out of 9 patients (77.8%) after 2 courses of FLAG regimen, however one patient failed to obtain sufficient CD34(+) cells after 3 courses. 6 patients received autologous stem cell transplantation, 3 patients received allogeneic stem cell transplantation, and 7 cases received 2 courses of Ara-c after treating with mitoxantrone or daunorubicin. One patient died within 4 weeks. 9 patients relapsed. The median survival duration was 14 (1 - 46) months and median disease-free survival time was 12 (2 - 45) months. There was no significant difference for OS and DFS between IA and non-IA groups. Myelosuppression and infections due to neutropenia were the most frequent adverse effects, severe nonhematologic toxicities were not observed in all patients. It is concluded that as consolidation regimen, the FLAG is an effective and well-tolerated treatment in AML with acceptable toxicity, and may not influence the peripheral stem cell mobilization for autologous stem cell transplantation after 2 courses of FLAG.
本研究的目的主要是探讨大剂量阿糖胞苷、氟达拉滨和粒细胞集落刺激因子(FLAG)联合方案作为急性髓系白血病(AML)患者巩固治疗的疗效,并分析FLAG对外周血干细胞动员的影响。31例完全缓解的AML患者根据诱导方案分为两组,即IA组(去甲氧柔红霉素和阿糖胞苷)和非IA组。所有患者均采用FLAG方案巩固治疗,具体为:氟达拉滨50mg/d,第1 - 5天;阿糖胞苷2g/(m²·d),第1 - 5天;粒细胞集落刺激因子300μg/d。使用时间从第0天持续至绝对中性粒细胞计数>1.0×10⁹/L。17例患者接受2或3个疗程的FLAG方案,14例患者接受1个疗程。9例患者接受2个疗程的FLAG方案作为巩固治疗,随后采集外周血干细胞。结果显示,9例患者中7例(77.8%)在接受2个疗程的FLAG方案后获得了足够的外周血干细胞,然而1例患者在接受3个疗程后未能获得足够的CD34⁺细胞。6例患者接受了自体干细胞移植,3例患者接受了异基因干细胞移植,7例患者在接受米托蒽醌或柔红霉素治疗后接受了2个疗程的阿糖胞苷治疗。1例患者在4周内死亡。9例患者复发。中位生存时间为14(1 - 46)个月,中位无病生存时间为12(2 - 45)个月。IA组和非IA组之间的总生存期(OS)和无病生存期(DFS)无显著差异。骨髓抑制和中性粒细胞减少引起的感染是最常见的不良反应,所有患者均未观察到严重的非血液学毒性。结论是,作为巩固方案,FLAG方案治疗AML有效且耐受性良好,毒性可接受,并且在2个疗程的FLAG方案后可能不影响自体干细胞移植的外周血干细胞动员。