粒细胞集落刺激因子与粒细胞-巨噬细胞集落刺激因子联合应用动员造血祖细胞的I/II期研究

Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.

作者信息

Winter J N, Lazarus H M, Rademaker A, Villa M, Mangan C, Tallman M, Jahnke L, Gordon L, Newman S, Byrd K, Cooper B W, Horvath N, Crum E, Stadtmauer E A, Conklin E, Bauman A, Martin J, Goolsby C, Gerson S L, Bender J, O'Gorman M

机构信息

Robert Lurie Cancer Center, Northwestern University, Chicago, IL 60611, USA.

出版信息

J Clin Oncol. 1996 Jan;14(1):277-86. doi: 10.1200/JCO.1996.14.1.277.

DOI:10.1200/JCO.1996.14.1.277

PMID:8558209

Abstract

PURPOSE

To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs).

MATERIALS AND METHODS

Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest.

RESULTS

The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001).

CONCLUSION

Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.

摘要

目的

研究联合应用粒细胞集落刺激因子（G-CSF）和粒细胞巨噬细胞集落刺激因子（GM-CSF）动员造血祖细胞（HPC）的毒性和疗效。

材料与方法

每组至少5例患者，皮下给药，具体如下：第1至12天给予G-CSF 5微克/千克，第7至12天给予GM-CSF 0.5、1或5微克/千克（第1、2和3组）；第1至12天给予GM-CSF 5微克/千克，第7至12天给予G-CSF 5微克/千克（第4组）；第1至12天给予G-CSF和GM-CSF各5微克/千克（第5组）。在第1天（基线，CSF治疗前）、第5、7、11和13天进行10升血液成分单采。每次采集后进行粒细胞巨噬细胞集落形成单位（CFU-GM）和红系爆式集落形成单位（BFU-E）的集落测定。

结果

主要毒性为肌痛、骨痛、发热、恶心和轻度血小板减少，但均无剂量限制性。单独使用G-CSF或GM-CSF治疗4天，导致每次采集每千克所收集的CFU-GM数量显著且持续增加，分别比基线增加35.6±8.9倍和33.7±13.0倍。这种增加既归因于每10升血液成分单采所收集的单核细胞数量增加，也归因于每次采集中祖细胞浓度的增加。在已接受GM-CSF治疗的患者中给予G-CSF（第4组），使HPC含量激增至基线的近80倍（P = 0.024）；相反顺序，即在G-CSF基础上加用GM-CSF，则效果较差。基线血液成分单采的CFU-GM含量与实现的最大动员相关（r = 0.74，P = 0.001）。