Wörmann B, Hiddemann W, Frisch J, Zühlsdorf M, Rottmann R, Boeckmann A, Reuter C, Freire E A, Innig G, Schulz G
Department of Internal Medicine A, University of Münster, University Hospital, Germany.
Behring Inst Mitt. 1991 Dec(90):28-38.
70% of patients with newly diagnosed and 50% of patients with relapsed acute myeloid leukemia (AML) can achieve a complete remission with intensive chemotherapy. However, the treatment-associated mortality can be as high as 30% increasing with age, previous chemotherapy and intensity of chemotherapy. GM-CSF was first applied in 36 patients with high risk AML after chemotherapy to reduce the time of critical neutropenia. The early death rate was significantly lower in the GM-CSF group compared to 56 patients of a historic control group with similar risk factors and identical chemotherapy (p less than 0.009). The rate of complete remissions was also significantly higher in the GM-CSF group (p less than 0.09). More recently, GM-CSF was used as a priming agent 24 h prior to start of chemotherapy. 25 patients have entered the study up to now. The cell biological effects of GM-CSF in vivo include an immediate increase of leukemic blasts and of normal myeloid cells in the peripheral blood with a median of 2.0, an increase of cells in the S-phase of the cell cycle in bone marrow biopsies, an increase in DNA polymerase activity, an increase in Ara-C cytotoxicity and immunophenotypic changes compatible with differentiation of leukemic blasts along the pathway of normal myeloid progenitors. GM-CSF has a dual effect on normal and leukemic myeloid cells. It can be safely applied in patients with AML. Prospective randomized trials have to be performed to establish its role in reducing treatment toxicity and in improving the overall treatment results.
70%的新诊断急性髓系白血病（AML）患者和50%的复发AML患者通过强化化疗可实现完全缓解。然而，与治疗相关的死亡率可能高达30%，且会随着年龄、既往化疗情况及化疗强度的增加而升高。GM - CSF最初应用于36例化疗后的高危AML患者，以缩短严重中性粒细胞减少的时间。与具有相似危险因素且接受相同化疗的56例历史对照组患者相比，GM - CSF组的早期死亡率显著更低（p小于0.009）。GM - CSF组的完全缓解率也显著更高（p小于0.09）。最近，GM - CSF在化疗开始前24小时被用作启动剂。截至目前，已有25例患者进入该研究。GM - CSF在体内的细胞生物学效应包括外周血中白血病原始细胞和正常髓系细胞立即增加，中位数为2.0，骨髓活检中细胞周期S期的细胞增加，DNA聚合酶活性增加，阿糖胞苷细胞毒性增加以及与白血病原始细胞沿正常髓系祖细胞途径分化相符的免疫表型改变。GM - CSF对正常和白血病髓系细胞具有双重作用。它可安全应用于AML患者。必须进行前瞻性随机试验以确定其在降低治疗毒性和改善总体治疗结果方面的作用。
