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: 6236427
• 负责人: NORMA K RAMSAY
• 金额: $ 2.48万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-01-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6236427
• 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; minimal residual disease; 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.

这部分补助金的目的是提高长期生存率 高危急性淋巴细胞白血病（ALL）患者。 这将是 利用同种异体、自体和无关供体进行骨髓移植 移植 将发生生物分层， 将接受同种异体匹配的同胞骨髓。 为 对于缺乏供体的患者，如果患者的血液中含有 四个月内找到无关的捐赠者。 患者， 找不到无关的捐献者将接受净化的自体骨髓。 用B或T特异性免疫毒素净化骨髓， 4-氢过氧环磷酰胺。 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 疗法 使用白细胞介素-2（IL-2）的移植后免疫刺激将 在自体B系白血病的I期和11项研究中进行评价 患者 这些试验将扩展到接受同种异体移植的患者。 或不相关的移植。 此外，一种新的移植前 使用免疫毒素进行调节治疗。 安全性， 抗CD 19单克隆抗体的耐受性和有效性 将评估美洲商陆抗病毒蛋白（B43-PAP）。 试点研究将 在所有B系患者中进行，包括接受 自体、同种异体和无关移植， 复发率。 这部分补助金的第二个目的是 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后确定。 移植后，使用 定量分析系统结合了多参数流式细胞术和 用白血病祖细胞进行细胞分选（LPC测定）。 这些 在移植前和第28天对所有患者进行评估 和第100天，以评估残留的 白血病