Markasz Laszlo, Stuber György, Flaberg Emilie, Jernberg Asa Gustafsson, Eksborg Staffan, Olah Eva, Skribek Henriette, Szekely Laszlo
Department of Microbiology, Tumor and Cell Biology and Center for Integrative Recognition in the Immune System, Karolinska Institute, Box 280 S-17177 Stockholm, Sweden.
BMC Cancer. 2006 Nov 13;6:265. doi: 10.1186/1471-2407-6-265.
Epstein-Barr virus (EBV) is the causative agent of immunosuppression associated lymphoproliferations such as post-transplant lymphoproliferative disorder (PTLD), AIDS related immunoblastic lymphomas (ARL) and immunoblastic lymphomas in X-linked lymphoproliferative syndrome (XLP). The reported overall mortality for PTLD often exceeds 50%. Reducing the immunosuppression in recipients of solid organ transplants (SOT) or using highly active antiretroviral therapy in AIDS patients leads to complete remission in 23-50% of the PTLD/ARL cases but will not suffice for recipients of bone marrow grafts. An additional therapeutic alternative is the treatment with anti-CD20 antibodies (Rituximab) or EBV-specific cytotoxic T-cells. Chemotherapy is used for the non-responding cases only as the second or third line of treatment. The most frequently used chemotherapy regimens originate from the non-Hodgkin lymphoma protocols and there are no cytotoxic drugs that have been specifically selected against EBV induced lymphoproliferative disorders.
As lymphoblastoid cell lines (LCLs) are well established in vitro models for PTLD, we have assessed 17 LCLs for cytotoxic drug sensitivity. After three days of incubation, live and dead cells were differentially stained using fluorescent dyes. The precise numbers of live and dead cells were determined using a custom designed automated laser confocal fluorescent microscope.
Independently of their origin, LCLs showed very similar drug sensitivity patterns against 29 frequently used cytostatic drugs. LCLs were highly sensitive for vincristine, methotrexate, epirubicin and paclitaxel.
Our data shows that the inclusion of epirubicin and paclitaxel into chemotherapy protocols against PTLD may be justified.
爱泼斯坦-巴尔病毒（EBV）是免疫抑制相关淋巴细胞增殖性疾病的病原体，如移植后淋巴细胞增殖性疾病（PTLD）、艾滋病相关免疫母细胞淋巴瘤（ARL）以及X连锁淋巴细胞增殖综合征（XLP）中的免疫母细胞淋巴瘤。据报道，PTLD的总体死亡率通常超过50%。降低实体器官移植（SOT）受者的免疫抑制或在艾滋病患者中使用高效抗逆转录病毒疗法可使23%至50%的PTLD/ARL病例完全缓解，但这对骨髓移植受者来说并不足够。另一种治疗选择是用抗CD20抗体（利妥昔单抗）或EBV特异性细胞毒性T细胞进行治疗。化疗仅在无反应的病例中作为二线或三线治疗使用。最常用的化疗方案源自非霍奇金淋巴瘤方案，且没有专门针对EBV诱导的淋巴细胞增殖性疾病选择的细胞毒性药物。
由于淋巴母细胞系（LCLs）是PTLD成熟的体外模型，我们评估了17个LCLs对细胞毒性药物的敏感性。孵育三天后，使用荧光染料对活细胞和死细胞进行差异染色。使用定制设计的自动激光共聚焦荧光显微镜确定活细胞和死细胞的精确数量。
无论其来源如何，LCLs对29种常用的细胞生长抑制剂显示出非常相似的药物敏感性模式。LCLs对长春新碱、甲氨蝶呤、表柔比星和紫杉醇高度敏感。
我们的数据表明，在针对PTLD的化疗方案中加入表柔比星和紫杉醇可能是合理的。
