Löwenberg Bob, van Putten Wim, Theobald Matthias, Gmür Jurg, Verdonck Leo, Sonneveld Pieter, Fey Martin, Schouten Harry, de Greef Georgine, Ferrant Augustin, Kovacsovics Tibor, Gratwohl Alois, Daenen Simon, Huijgens Peter, Boogaerts Marc
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
N Engl J Med. 2003 Aug 21;349(8):743-52. doi: 10.1056/NEJMoa025406.
Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML).
In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups.
After induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006).
Sensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML.
用造血生长因子使白血病细胞致敏可能会增强急性髓系白血病（AML）化疗的细胞毒性。
在一项多中心随机试验中，我们将新诊断的AML患者（年龄范围18至60岁）分配为接受阿糖胞苷加伊达比星（第1周期）和阿糖胞苷加安吖啶（第2周期），其中一组联合粒细胞集落刺激因子（G-CSF）（321例患者），另一组不使用G-CSF（319例）。G-CSF仅在化疗时同时给予。伊达比星和安吖啶在一个周期结束时给予，以使阿糖胞苷在G-CSF作用下的细胞周期依赖性细胞毒性产生更大效果。在所有患者以及细胞遗传学不同的预后亚组中评估G-CSF对无病生存的影响。
诱导化疗后，两组的缓解率无显著差异。中位随访55个月后，诱导化疗加G-CSF后达到完全缓解的患者无病生存率高于未接受G-CSF治疗的患者（4年时分别为42%和33%，P=0.02），原因是复发概率降低（相对风险0.77；95%置信区间0.61至0.99；P=0.04）。G-CSF未显著改善总生存（P=0.16）。虽然G-CSF未改善预后不良亚组的结局，但72%的标准风险AML患者从G-CSF治疗中获益（4年总生存为45%，未接受G-CSF治疗组为35%[死亡相对风险0.75；95%置信区间0.59至0.95；P=0.02]；无病生存为45%对33%[相对风险0.70]；95%置信区间0.55至0.90；P=0.006）。
用生长因子使白血病细胞致敏是增强AML患者化疗疗效的一种临床可用方法。
