HIGH DOSE CHEMO & STEM CELL TRANSPLANT IN HIV NON HODGKINS LYMPHOMA

这是一项I期研究，旨在评估基因工程自体CD34外周血祖细胞（PBPC）在接受非霍奇金淋巴瘤（NHL）治疗的HIV+患者中的安全性、移植和相对存活率。患有艾滋病和非hl的成年受试者如果对化疗有初步反应，CD4计数为100/ml，并且没有活动性机会性感染，则符合本研究的资格。在初始化疗后，受试者将进行自体PBPC移植。PBPC将通过细胞因子G-CSF的动员和分离从外周血中富集。移植前，三分之二的分离产物将被选择用于PBPC，分为两个培养，在含有细胞因子IL-3， IL-6和SCF的生长培养基中在自体基质培养物上生长三天。在此期间，一种培养物将用含有抗艾滋病毒双核酶基因的逆转录病毒载体进行转导，这种逆转录病毒载体直接指向艾滋病毒的转录区和转录区，另一种培养物将用不编码核酶的对照载体进行转导。这两种培养的工程细胞将被混合并注入受试者体内。然后注入未转导的干细胞。输注后，第1天和第1、3、6、9、12、18和24个月的血液样本和第1、3、6、12和24个月的骨髓样本的比例。与含有中性标记基因的细胞相比，含有抗hiv -1 TR/TAT核酶基因的细胞频率相对增加，这意味着抗hiv -1核酶赋予了细胞选择性生存优势。该研究的具体目的是：1)评估使用编码抗HIV双核酶的逆转录病毒载体转导的PBPC对接受NHL强化化疗和干细胞移植的HIV阳性患者的安全性和可行性。2)确定这些基因修饰的PBPC能否移植、分化并在移植受者血液中循环。3)比较核酶载体转导PBPC后代细胞与外周对照载体标记细胞的存活率。4)评价大剂量化疗联合干细胞移植对HIV+ NHL患者的毒性和无病生存期。

This is a phase I study to evaluate the safety, engraftment and relative survival of genetically engineered autologous CD34 peripheral blood progenitor cells (PBPC) in HIV+ persons undergoing therapy for non-Hodgkin's lymphoma (NHL). Adult subjects with AIDS and NHL will be eligible for this study if they had an initial response to chemotherapy and have CD4 counts & 100/ml and are free of active opportunistic infections. After initial chemotherapy, subjects will undergo autologous PBPC transplantation. PBPC will be enriched from peripheral blood by mobilization with the cytokine G-CSF followed by apheresis. Prior to transplantation, two thirds of the apheresis product will be selected for PBPC, divided into two cultures, and grown on autologous stromal cultures for three days in growth medium containing the cytokines IL-3, IL-6, and SCF. During this time one culture will be transduced with a retroviral vector containing the anti-HIV double-ribozyme genes, which is directed toward the HIV tat and rev regions and the second culture will be transduced with a control vector that does not encode for a ribozyme. The two cultures of engineered cells will be mixed and infused into the subject. The untransduced stem cells will then be infused. Following infusions, the ratios of blood samples obtained at day +1 and months 1, 3, 6, 9, 12,18, and 24 and from marrow samples obtained at 1, 3, 6, 12, and 24 months. A relative increase in the frequency of cells containing the anti-HIV-1 TR/TAT ribozyme gene, compared to cells with the neutral marker gene, would imply that a selective survival advantage has been conferred to the cells by the anti-HIV-1 ribozymes. The specific aims of the study are: 1) to assess the safety and feasibility of administering PBPC transduced with retroviral vectors encoding an anti-HIV double ribozyme to HIV+ subjects undergoing intensive chemotherapy and stem cell transplantation for NHL. 2) To determine whether these genetically modified PBPC can engraft, differentiate, and circulate in the blood of transplanted recipients. 3) To determine the comparative survival of ribozyme-vector transduced PBPC progeny cells versus control vector marked cells in the periphery. 4) To evaluate the toxicity and disease-free survival of high dose chemotherapy with stem cell transplantation in HIV+ subjects with NHL.