ACUTE LYMPHOBLASTIC LEUKEMIA--AUTOLOGOUS AND ALLOGENEIC TRANSPLANTATION

急性淋巴细胞白血病——自体和同种异体移植

• 批准号: 5206945
• 负责人: NORMA K RAMSAY
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5206945
• 关键词: acute lymphocytic leukemia; autologous transplantation; bone marrow transplantation; clinical trials; flow cytometry; homologous transplantation; human subject; human therapy evaluation; immunoconjugates; immunotoxicity; interleukin 2; neoplasm /cancer relapse /recurrence; neoplasm /cancer remission /regression

The objective of this section of the grant is to improve long term survival in high risk acute lymphoblastic leukemia (ALL) patients. This will be done utilizing allogeneic, autologous and unrelated donors for bone marrow transplantation. A biological stratification will occur whereby patients with matched siblings will receive allogeneic matched sibling marrow. For patients who lack donors, an unrelated donor transplant will be used if an unrelated donor is found within four months. Patients for whom an unrelated donor cannot be found will receive purged autologous bone marrow. Purging the marrow will be with B or T specificity immunotoxins and 4-hydroperoxycyclophosphamide. To decrease the post-transplant relapse rate, these patients will receive additional pre- and post-transplant therapy. Post-transplant immunostimulation using interleukin-2 (IL-2) will be evaluated in phase I and 11 studies in autologous B lineage leukemia patients. These trials will he extended to patients undergoing allogeneic or unrelated transplant as appropriate. In addition, a new pre-transplant conditioning therapy will be utilized employing immunotoxins. The safety, tolerance and efficacy of an anti-CD 19 monoclonal antibody linked to pokeweed antiviral protein will be evaluated (B43-PAP). Pilot studies will be performed in all B-lineage patients including those undergoing autologous, allogeneic and unrelated transplant in an effort to decrease their relapse rate. A secondary objective of this section of the grant is to evaluate the prognostic value of residual leukemic progenitor cells. The quality of remission will be determined in patients pre- and post-transplant to evaluate the impact of minimal residual disease using a quantitative assay system which combines multiparameter flow cytometry and cell sorting with leukemia progenitor cells (LPC assays). These evaluations will be performed in all patients pre-transplant and at day 28 and day 100 in an effort to evaluate the prognostic role of residual leukemia.

这部分赠款的目的是为了提高长期存活率。 在高危急性淋巴细胞白血病(ALL)患者中。这将是 利用同种异体、自体和无血缘关系的供者进行骨髓移植 移植。生物分层将会发生，因此患者 匹配的兄弟姐妹将接受异基因匹配的兄弟姐妹骨髓。为 如果患者缺乏供者，则将使用无血缘关系的供者移植 无血缘关系的捐献者在四个月内被找到。为其提供服务的患者 无法找到无血缘关系的供者将接受净化的自体骨髓。 净化骨髓将使用B或T特异性免疫毒素和 4-羟基过氧环磷酰胺。减少移植后复发 ，这些患者将在移植前和移植后接受额外的治疗 心理治疗。移植后使用白介素2(IL-2)的免疫刺激将 在自体B系白血病的I期和11期研究中进行评估 病人。这些试验将扩大到接受异基因移植的患者。 或不相关的移植。此外，一种新的移植前 将使用免疫毒素进行条件反射治疗。安全， 抗CD19单抗的耐受性和有效性 将评估商陆抗病毒蛋白(B43-PAP)。试点研究将 适用于所有B系患者，包括那些正在接受 自体、异体和无关的移植，以努力减少 他们的复发率。这一部分赠款的次要目标是 目的：评价残留白血病祖细胞的预后价值。 缓解的质量将在患者治疗前和治疗前确定。 移植后评估微小残留病的影响 多参数流式细胞仪与多参数联合定量检测系统 白血病祖细胞分选(LPC法)。这些 将在移植前和第28天对所有患者进行评估 和第100天，以努力评估残留物的预后作用 白血病。