Büchner T, Hiddemann W, Wörmann B, Zühlsdorf M, Rottmann R, Innig G, Maschmeier G, Ludwig W D, Sauerland M C, Heinecke A
University of Münster Medical Center, Germany.
Semin Oncol. 1997 Feb;24(1):124-31.
Hematopoietic growth factors (GFs) are administered to patients who have acute myeloid leukemia (AML) in order to overcome two limitations of chemotherapy: (I) myelotoxicity, and (2) the chemoresistance of minimal residual disease. GFs have been used after chemotherapy in 11 clinical studies, 8 on older age or otherwise high-risk AML. The GFs used were granulocyte-macrophage colony-stimulating factor (GM-CSF) in 7, G-CSF in three and macrophage-CSF in one of the studies. Beneficial effects could be shown on the duration of neutropenia in 8 studies, frequency of infections or fever in 4 studies, mortality or survival in 2 studies and remission rate in 1 study. The benefits in remissions and survival were all found among high-risk patients. One study in younger patients found disadvantages in the remission rate and event-free survival, whereas there was no adverse effect of GF on therapy resistance, leukemic regrowth, or disease-free survival in the other studies. GF priming strategies are based on their stimulation of AML blasts in vitro, their modulation of cellular cytarabine (ARA-C) metabolism and enhancement of clonogenic cell kill by ARA-C. Protective effects of GF against clonogenic cell kill or apoptosis were also described. There are data from 10 clinical studies using GFs before or simultaneously with chemotherapy. One study showed significance, two others a tendency to longer disease-free survival, and two studies showed a trend toward more remissions. A disadvantage in the remission rate and survival was found in one study and prolonged thrombocytopenia in two studies. Nine of ten studies did not find evidence for an adverse effect of GF priming on the course of the disease. In most studies, GF priming was only administered in one or two chemotherapy courses. One study giving four to five courses found a reduction in relapses during the first 6 months. In conclusion, a supportive use of GF may have a place in high-risk, but not standard-risk AML. GF priming approaches may not have been adequately investigated and an extension of this strategy to more treatment courses now appears more promising. Based on the clinical data available, all administration of GF in AML should be regarded as investigational.
造血生长因子（GFs）被用于治疗急性髓系白血病（AML）患者，以克服化疗的两个局限性：（1）骨髓毒性，以及（2）微小残留病的化疗耐药性。在11项临床研究中，GFs在化疗后被使用，其中8项针对老年或其他高危AML患者。所使用的GFs在7项研究中为粒细胞巨噬细胞集落刺激因子（GM-CSF），3项研究中为G-CSF，1项研究中为巨噬细胞集落刺激因子。在8项研究中可显示出对中性粒细胞减少持续时间的有益作用，4项研究中显示出对感染或发热频率的有益作用，2项研究中显示出对死亡率或生存率的有益作用，1项研究中显示出对缓解率的有益作用。缓解和生存方面的益处均在高危患者中发现。一项针对年轻患者的研究发现缓解率和无事件生存率存在劣势，而在其他研究中GF对治疗耐药性、白血病再生或无病生存率没有不良影响。GF启动策略基于其在体外对AML原始细胞的刺激、对细胞阿糖胞苷（ARA-C）代谢的调节以及增强ARA-C对克隆形成细胞的杀伤作用。还描述了GF对克隆形成细胞杀伤或凋亡的保护作用。有10项临床研究的数据，这些研究在化疗前或同时使用GFs。一项研究显示有显著意义，另外两项研究显示无病生存期有延长趋势，两项研究显示缓解有增加趋势。一项研究发现缓解率和生存率存在劣势以及两项研究发现血小板减少持续时间延长。十项研究中有九项未发现GF启动对疾病进程有不良影响的证据。在大多数研究中，GF启动仅在一两个化疗疗程中使用。一项给予四到五个疗程的研究发现前6个月复发率降低。总之，GF的支持性使用在高危而非标准风险的AML中可能有一席之地。GF启动方法可能尚未得到充分研究，现在将该策略扩展到更多治疗疗程似乎更有前景。基于现有的临床数据，AML中GF的所有应用都应视为试验性的。
