EFFECT OF RECOMBINANT HUMAN GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR ON HEMATOPOIETIC RECONSTITUTION AFTER HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS BONE-MARROW TRANSPLANTATION
EFFECT OF RECOMBINANT HUMAN GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR ON HEMATOPOIETIC RECONSTITUTION AFTER HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS BONE-MARROW TRANSPLANTATION
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DOI：
10.1056/nejm198804073181401
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发表时间：
1988-04-07
影响因子：
158.5
通讯作者：
OETTE, DH
中科院分区：
文献类型：
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作者：
BRANDT, SJ;PETERS, WP;OETTE, DH
据报道，重组人粒细胞-巨噬细胞集落刺激因子（rHuGM-CSF）可增加接受全身照射的非人灵长类动物和获得性免疫缺陷综合征患者的白细胞计数。我们给19名接受高剂量联合化疗和自体骨髓支持治疗的乳腺癌或黑色素瘤患者服用这种物质。在骨髓输注后3小时开始，用2.0、4.0、8.0、16.0或32.0 μ g/kg体重/天的糖基化rHuGM-CSF连续静脉输注治疗3或4名患者的组14天。与年龄、诊断和治疗相匹配的24例历史对照相比，这些患者的总白细胞和粒细胞恢复加速。白细胞计数（平均值±. SD）为1511. ±.在每天给予2 - 8 μ g/kg的患者中为1003/μ l，在每天给予2575 ± 1003/μ l的患者中为2575 ± 1003/μ l。给予16 μ g的受试者为2304，给予16 μ g的受试者为3120 ±。在给予32 μ g的那些中为1744，相比之下为863 ±。对照组每微升645。未观察到对血小板计数的一致影响。毒性作用通常是轻微的，并且在每天给予2至16 μ g/kg的患者中没有明显的剂量相关性。所有给予32 μ g/kg的患者均出现水肿、体重增加或肌痛;两名患者出现明显的体重增加、全身水肿、胸腔积液和低血压，其中一名患者还出现急性肾衰竭。我们的研究结果表明，rHuGM-CSF可以加速高剂量化疗和自体骨髓移植后的骨髓恢复，在可以耐受的剂量范围内。在这种情况下，增加剂量的能力受到肌痛和液体潴留的限制。
Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) has been reported to increase the leukocyte count in subhuman primates subjected to total-body irradiation and in patients with the acquired immunodeficiency syndrome. We administered this substance to 19 patients with breast cancer or melanoma treated with high-dose combination chemotherapy and autologous bone marrow support. Groups of three or four patients were treated with 2.0, 4.0, 8.0, 16.0, or 32.0 .mu.g per kilogram of body weight per day of glycosylated rHuGM-CSF by continuous intravenous infusion for 14 days, beginning three hours after bone marrow infusion. Total leukocyte and granulocyte recovery was accelerated in these patients as compared with 24 historical controls matched for age, diagnosis, and treatment. Leukocyte counts (mean .+-.SD) obtained 14 days after transplantation were 1511.+-.1003 per microliter in patients given 2 to 8 .mu.g per kilogram per day, 2575.+-.2304 in those given 16.mu.g, and 3120.+-.1744 in those given 32 .mu.g, as compared with 863.+-.645 per microliter in the controls. No consistent effect on platelet counts was noted. Toxic effects were generally mild and not clearly dose-related in patients given 2 to 16 .mu.g per kilogram per day. Edema, weight gain, or myalgias occurred in all patients given 32 .mu.g per kilogram; marked weight gain, generalized edema, pleural effusions, and hypotension developed in two patients, one of whom also had acute renal failure. Our results indicate that rHuGM-CSF can accelerate myeloid recovery after high-dose chemotherapy and autologous bone marrow transplantation, over a range of doses that can be tolerated. In this setting the ability to increase the dose is limited by the development of myalgias and fluid retention.