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喷司他丁的免疫抑制作用。

Immunosuppressive effects of pentostatin.

作者信息

Kraut E H, Neff J C, Bouroncle B A, Gochnour D, Grever M R

机构信息

Department of Internal Medicine, Ohio State University, Columbus 43210.

出版信息

J Clin Oncol. 1990 May;8(5):848-55. doi: 10.1200/JCO.1990.8.5.848.

Abstract

The immune function of patients with hairy cell leukemia (HCL) and solid tumors was evaluated before and after treatment with the investigational drug 2'-deoxycoformycin (pentostatin; dCF). Thirteen HCL patients received doses of dCF of 2 to 4 mg/m2 intravenously at 2- to 6-week intervals for up to 15 courses. After completion of treatment, 12 of 13 patients had resolution of severe monocytopenia and five of nine had normal monocyte antibody dependent cellular cytotoxicity. There was statistically significant depression of total lymphocytes, T cells, and B cells. Evaluation of T subsets showed a decrease in CD4+ cells. Immunoglobulin G (IgG) in sera were decreased from baseline, while IgM and IgA were unaffected. There was no significant effect on skin-test reactivity or large granular lymphocyte numbers. Lymphoblastic transformation was variably affected. Natural-killer (NK) cell function was improved or unchanged after dCF treatment. Reevaluation of seven patients at 21 to 119 weeks after receiving dCF demonstrated that recovery to normal T- and B-cell numbers and subsets does occur. Five solid tumor patients were given dCF at 4 mg/m2 intravenously at 1- to 2-week intervals for up to five courses. There was significant reduction in T cells, B cells, CD4+, and CD8+ cells with no statistically significant effect on the other immune parameters. We conclude that low doses of dCF can cause persistent immunosuppression though recovery may occur after the drug is stopped. In patients followed after completion of dCF, there was no associated increase in second malignancies or unusual infections.

摘要

对毛细胞白血病(HCL)患者和实体瘤患者在使用研究性药物2'-脱氧助间型霉素(喷司他丁;dCF)治疗前后的免疫功能进行了评估。13例HCL患者以2至6周的间隔静脉注射剂量为2至4mg/m²的dCF,最多进行15个疗程。治疗结束后,13例患者中有12例严重单核细胞减少症得到缓解,9例中有5例单核细胞抗体依赖性细胞毒性恢复正常。总淋巴细胞、T细胞和B细胞有统计学意义的减少。T细胞亚群评估显示CD4⁺细胞减少。血清中的免疫球蛋白G(IgG)较基线水平降低,而IgM和IgA未受影响。对皮肤试验反应性或大颗粒淋巴细胞数量无显著影响。淋巴细胞转化受到不同程度的影响。dCF治疗后自然杀伤(NK)细胞功能改善或未改变。在接受dCF后21至119周对7例患者进行重新评估,结果表明T细胞和B细胞数量及亚群确实恢复到了正常水平。5例实体瘤患者以1至2周的间隔静脉注射4mg/m²的dCF,最多进行5个疗程。T细胞、B细胞、CD4⁺和CD8⁺细胞显著减少,对其他免疫参数无统计学意义的显著影响。我们得出结论,低剂量的dCF可导致持续性免疫抑制,尽管停药后可能会恢复。在完成dCF治疗后随访的患者中,未发现继发性恶性肿瘤或异常感染有相关增加。

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