DONOR LYMPHOCYTES TRANSDUCED WITH HERPES SIMPLEX THYMIDINE KINASE GENE

本研究将评价异基因骨髓移植（BMT）后复发性恶性血液病或爱泼斯坦巴尔病毒嗜酸性增殖综合征（EBV-LPS）患者接受异基因供体淋巴细胞输注的安全性和有效性。 供体淋巴细胞输注已导致一些异基因BMT后复发性白血病或淋巴组织增生性疾病患者的治愈，但移植物抗宿主病（GvHD）的发展使其复杂化。 我们假设，含有单纯疱疹胸苷激酶（HStk）基因的逆转录病毒载体将允许过继免疫治疗的抗白血病反应，同时允许选择性破坏这些细胞。 理论上，这应该允许评估移植物抗白血病（GvL）效应和终止不想要的程度的GvHD。 在同种异体BMT后复发的恶性血液病或EBV-LPS患者将输注离体基因修饰的供体淋巴细胞。 使用PA 317/LTKOSN.2载体上清液将HStk基因离体转导到细胞中。 将HStk基因插入淋巴细胞可使其对抗疱疹药物更昔洛韦（GCV）敏感。 如果发生移植物抗宿主病，这种原位选择性破坏供体淋巴细胞将用于消除移植物抗宿主病的影响。

This study will evaluate the safety and efficacy of allogeneic donor lymphocyte infusions in patients who have relapsed hematologic malignancies or Epstein Barr Virus Lymphoproliferative Syndrome (EBV-LPS) after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow the anti-leukemia response of adoptive immunotherapy while allowing for selective destruction of these cells. Theoretically this should allow appreciation of graft versus leukemia (GvL) effect and termination of an unwanted degree GvHD. Patients with relapsed hematologic malignancies or EBV-LPS after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The HStk gene will be transduced into the cells ex vivo using PA317/LTKOSN.2 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effects of graft versus host disease, if it develops.