The prognostic role of CD4+ and CD8+ lymphocytes during chemoimmunotherapy in metastatic melanoma

The prognostic role of CD4+ and CD8+ lymphocytes during chemoimmunotherapy in metastatic melanoma
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DOI:
10.1097/00008390-200412000-00009
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发表时间:
2004-12-01
期刊:
影响因子:
2.2
通讯作者:
Pyrhönen, SO
Pyrhönen, SO
中科院分区:
医学4区
文献类型:
--
作者:
Hernberg, MM;Hahka-Kemppinen , MH;Pyrhönen, SO

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我们观察到,在化疗免疫治疗期间,转移性黑色素瘤患者CD4+/CD8+比值的早期增加是最有利的独立预后因素。在本研究中,87例转移性黑色素瘤患者在化疗免疫治疗(达卡巴嗪、长春花碱、依莫司汀和博来霉素或达卡巴嗪单独加干扰素- α)之前和期间监测外周血淋巴细胞亚群(CD4+和CD8+),以证实我们之前的观察。系统地从接受这些化学免疫疗法中的任何一种的患者中获取血液样本。利用单克隆抗体OKT4 (CD4+, t辅助细胞)和OKT8 (CD8+, t抑制细胞),流式细胞术监测外周血淋巴细胞亚群的频率。总有效率为46.5%,中位总生存期为9.3个月。治疗前CD4+水平高于平均水平的患者,后来对治疗有反应,其中位生存期为28.1个月,而治疗前CD4+水平较低的应答者为10.2个月(P=0.053, log-rank检验)。CD8+水平降低的应答者的中位生存期为278个月,而CD8+水平升高的应答者的中位生存期为10.8个月(P= 0.04, log-rank检验)。同样,CD4+ /CD8 +比值升高的应答患者的中位生存期为28.1个月,而比值降低的应答患者的中位生存期为10.5个月(P=0.002, log-rank检验)。无论治疗前CD4+淋巴细胞的高低、CD8+水平的升高或降低、CD4+/CD8+比值的升高或降低,无应答者的中位生存期均无差异。这项随访研究证实,CD4+和CD8+淋巴细胞的监测可能为接受化学免疫治疗的转移性黑色素瘤患者提供重要的预测和预后信息。(C) 2004利平科特·威廉姆斯·威尔金斯。
We have observed that an early increase in the CD4+/CD8+ ratio of metastatic melanoma patients during chemoimmunotherapy is the most favourable independent prognostic factor. In this study, 87 patients with metastatic melanoma were monitored for peripheral blood lymphocyte subsets (CD4+ and CD8+) before and during chemoimmunotherapy (dacarbazine, vinblastine, Iomustine and bleomycin or dacarbazine alone plus interferon-alpha) to confirm our previous observation. Blood samples were systematically obtained from patients who received either of these chemoimmunotherapies. The frequencies of peripheral blood lymphocyte subsets were monitored by flow cytometry using monoclonal antibodies OKT4 (CD4+, T-helper cells) and OKT8 (CD8+, T-suppressor cells). The overall response rate was 46.5%, and the median overall survival was 9.3 months. Patients with pre-treatment CD4+ levels above the mean level, who later responded to therapy, had a median survival of 28.1 months vs. 10.2 months for responders with low pre-treatment CD4+ levels (P=0.053, log-rank test). Responders with decreasing CD8+ levels had a median survival of 278 months vs. 10.8 months for responders with increasing CD8+ levels (P= 0.04, log-rank test). Similarly, responding patients with an increasing CD4+ /CD8 + ratio had a median survival of 28.1 months vs. 10.5 months for those with decreasing ratios (P=0.002, log-rank test). Non-responders showed no difference in median survival irrespective of low or high pre-treatment CD4+ lymphocytes, increasing or decreasing CD8+ levels, or increasing or decreasing CD4+/CD8+ ratios. This follow-up study confirms that the monitoring of CD4+ and CD8+ lymphocytes may provide important predictive and prognostic information in metastatic melanoma patients receiving chemoimmunotherapy. (C) 2004 Lippincott Williams Wilkins.