EFFECTS OF RECOMBINANT HUMAN GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES
EFFECTS OF RECOMBINANT HUMAN GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES
复制标题
DOI：
10.1056/nejm198712173172501
复制
发表时间：
1987-12-17
影响因子：
158.5
通讯作者：
GUTTERMAN, JU
中科院分区：
文献类型：
--
作者：
VADHANRAJ, S;KEATING, M;GUTTERMAN, JU
骨髓增生异常综合征的特点是无效造血和难治性血细胞减少。为了改善造血功能，我们对8例骨髓增生异常综合征患者给予重组人粒细胞-巨噬细胞集落刺激因子（GM-CSF），作为I期试验的一部分。GM-CSF通过每天连续静脉输注给药，持续两周，然后在两周的休息期后再次给药。在测试的整个剂量范围内（30至500 μ g/m2体表面积），在所有8名患者中，治疗与外周血白细胞（5至70倍），包括粒细胞（5至373倍）的显著增加相关。所有患者的单核细胞、嗜酸性粒细胞和淋巴细胞的绝对数量均增加。8名患者中有3名患者的血小板计数增加2至10倍，红细胞生成改善，结果是3名需要红细胞和血小板输注的患者中有2名不再需要（随访20至27周）。治疗还与骨髓细胞结构增加和原始细胞过多患者骨髓中原始细胞百分比降低相关，导致分化髓样细胞与未成熟髓样细胞的比例增加。我们观察到相对较少的副作用，但当骨痛与高白细胞计数相关时，它是剂量限制性的。我们的研究结果表明，GM-CSF是一种有效的刺激体内造血，并可能在短期内（8至32周的观察）骨髓增生异常综合征患者的血液学改善。需要更多的经验和更长的随访期来评估这种新治疗的长期安全性和有效性。
The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period. Over the entire dose range tested (30 to 500 .mu.g per square meter of body-surface area), treatment was associated with marked increases in peripheral-blood leukocytes (5- to 70-fold), including granulocytes (5- to 373-fold), in all eight patients. The absolute number of monocytes, eosinophils, and lymphocytes increased in all patients. Three of eight patients also had 2- to 10-fold increases in platelet counts and improvement in erythropoiesis, with the result that two of three patients who had required red-cell and platelet transfusions no longer needed them (at 20 to 27 weeks of follow-up). Treatment was also associated with increased marrow cellularity and a decreased percentage of blasts in the bone marrow of patients with excess blasts, resulting in an increase in the ratio of differentiated myeloid cells to immature myeloid cells. We observed relatively few side effects, but bone pain was dose-limiting when it was associated with high white-cell counts. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome. More experience, with longer follow-up periods, will be necessary to assess the long-term safety and efficacy of this new treatment.