Department of Microbiology, Tumor and Cell Biology-MTC and Center for Integrative Recognition in the Immune System-IRIS, Karolinska Institute, Box 280 SE-17177 Stockholm, Sweden.
BMC Cancer. 2011 Oct 12;11:441. doi: 10.1186/1471-2407-11-441.
Primary effusion lymphoma (PEL) is a rare KSHV/HHV8-associated high-grade non-Hodgkin's lymphoma (NHL) of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected men with severe immunosuppression and other HHV8-associated diseases such as Kaposi's sarcoma (KS). The prognosis for those infected is poor, with a median survival of less than 6 months in most cohorts. Sustained complete remission is rare. High-dose chemotherapy regimens are used to improve remission rate and survival. The aim of the present study was to compare the drug sensitivity pattern of the available primary effusion (body cavity based) lymphoma-derived cell lines in order to find additional, potentially effective drugs that are not included in current chemotherapy treatment protocols.
We have analyzed 11 cell lines against 27 frequently used cytostatic drugs in short term (3 days) survival assays using automated high throughput confocal microscopy.
All cell lines showed a distinct, individual drug sensitivity pattern. Considering the in vitro used and clinically achieved drug concentration, Vinorelbine, Paclitaxel, Epirubicin and Daunorubicin were the most effective drugs.
We suggest that inclusion of the above drugs into PEL chemotherapy protocols may be justified. The heterogeneity in the drug response pattern however indicated that assay-guided individualized therapy might be required to optimize therapeutic response.
原发性渗出性淋巴瘤(PEL)是一种罕见的与卡波西肉瘤疱疹病毒(KSHV)/人类疱疹病毒 8 型(HHV8)相关的 B 细胞来源的高级别非霍奇金淋巴瘤(NHL),其特征是体腔中存在浆液性渗出液。大多数患者为 HIV 感染的男性,存在严重的免疫抑制和其他 HHV8 相关疾病,如卡波西肉瘤(KS)。受感染患者的预后较差,大多数队列的中位生存期均不足 6 个月。持续性完全缓解很少见。高剂量化疗方案用于提高缓解率和生存率。本研究旨在比较现有原发性渗出(基于体腔)淋巴瘤衍生细胞系的药物敏感性模式,以寻找尚未包含在当前化疗治疗方案中的其他潜在有效药物。
我们使用自动高通量共聚焦显微镜,在短期(3 天)生存测定中分析了 11 个细胞系对 27 种常用细胞毒药物的反应。
所有细胞系均表现出独特的个体药物敏感性模式。考虑到体外使用和临床达到的药物浓度,长春瑞滨、紫杉醇、表柔比星和柔红霉素是最有效的药物。
我们建议将上述药物纳入 PEL 化疗方案可能是合理的。然而,药物反应模式的异质性表明,可能需要基于检测的个体化治疗来优化治疗反应。