Nonmyeloablative Hematopoietic Cell Allotransplants

非清髓性造血细胞同种异体移植

• 批准号: 7226426
• 负责人: Rainer F. Storb
• 金额: $ 37.15万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7226426
• 关键词: Accelerated Phase; Acute; Acute Lymphocytic Leukemia; Age; Allogenic; Ambulatory Care; Autologous; Blast Phase; Busulfan/Cyclophosphamide; Busulfan/Fludarabine; Canis familiaris; Cell Transplantation; Cells; Characteristics; Chronic Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic-Phase Myeloid Leukemia; Class; Comorbidity; Comorbidity Index; Data; Diagnosis; Disease; Disease remission; Engraftment; Foundations; Fred Hutchinson Cancer Research Center; Graft vs Tumor Effect; HIV-1; Hematologic Neoplasms; Hematological Disease; Hematopoietic; Immunosuppression; Infection; Malignant - descriptor; Malignant Neoplasms; Medical; Modality; Modeling; Multiple Myeloma; Myeloproliferative disease; Numbers; Outcome; Patients; Prevention; Protocols documentation; Public Health; Randomized; Randomized Controlled Clinical Trials; Range; Safety; Staging; Therapeutic immunosuppression; Toxic effect; Translating; Treatment Protocols; Validation; cancer diagnosis; conditioning; graft vs host disease; human old age (65+); older patient; pre-clinical; prognostic; prospective; response; success; trial comparing

Project 1: Nonmyeloablative Hematopoietic Cell Allotransplants We propose to continue exploring nonmyeloablative conditioning regimens for allogeneic hematopoietic cell transplantation (HCT) in the treatment of patients with malignant blood disorders and those infected with human immunodeficiency virus 1 (HIV1). The principal regimens proposed have been translated from a preclinical canine model, use postgrafting immunosuppression to both enhance engraftment and control graft-vs-host disease (GVHD), rely on graft-vs-tumor effects for eradicating cancer, and can largely be administered in the ambulatory care setting owing to lack of serious regimen-related toxicities. The latter characteristic has enabled us to ignore the age and comorbidity limitations currently existing for myelo- ablative regimens. Given that and the fact that median ages at diagnoses for patients with most candidate diseases range from 65-70 years, the number of patients treatable and potentially curable by allogeneic HCT has been greatly increased. The first two Specific Aims will investigate HCT from HLA-matched and mismatched donors. While the focus is on unrelated HCT,several protocols will also include related donors. Two protocols are prospective randomized trials, one on prevention of acute GVHD, and one on outcomes for patients with myeldid malignancies given either myeloablative or nonmyeloablative conditioning. Several disease-specific protocols will assess the value of the nonmyeloablative HCT approach for patients with chronic myelocytic leukemia, Ph1+ acute lymphocytic leukemia, chronic lymphocytic leukemia, multiple myeloma, and patients with HIV1/AIDS. The third Aim will validate the prognostic value of a newly developed HCT-specific comorbidity index in a multi-center study. Almost all studies are being conducted under the auspices of a multi-institutional consortium which includes 17 academic centers outside of Seattle, and in which the Fred Hutchinson Cancer Research Center serves as the coordinating center. Relevance to Public Health: These proposed studies are aimed at increasing the safety of allogeneic HCT, a therapy already used to treat thousands of patients each year. Success in this project will broaden considerably the application of allogeneic HCT by allowing its use in elderly patients and others with additional medical problems. Further, the proposed regimen allows for'the purest determination of graft-vs- tumor effects, apart from intensive conditioning, and provides an excellent foundation on which to add disease-specific modalities. Finally, comorbidity data will likely become as important as defining cancer diagnosis, stage, remission status, and other more familiar variables in predicting patient response and outcome.

项目1：非甲状腺素造血细胞同倍移植植物 我们建议继续探索同种异体造血的非甲状腺素调节疗法 细胞移植（HCT）治疗恶性血液疾病患者和感染患者 与人类免疫缺陷病毒1（HIV1）。提议的主要方案已从 临床前犬模型，使用后修剪后的免疫抑制来增强植入和控制 移植-VS宿主疾病（GVHD），依赖于根除癌症的移植物-VS肿瘤作用，并且很大程度上可以是 由于缺乏严重的方案相关毒性，因此在门诊护理环境中管理。后者 特征使我们能够忽略Myelo-当前存在的年龄和合并症限制 消融方案。鉴于这一点以及大多数候选人患者的诊断中位数年龄 疾病范围为65 - 70年，可通过同种异体治疗的患者数量可治疗和可能治愈 HCT大大增加了。前两个具体目标将从HLA匹配的HCT调查，并 不匹配的捐助者。虽然重点是无关的HCT，但几个方案也将包括相关的捐助者。 两个方案是前瞻性随机试验，一项是预防急性GVHD，另一个关于结果 对于骨髓性或非乳不公动调理的肌动脉恶性肿瘤的患者。一些 特定于疾病的方案将评估非甲状腺素HCT方法的价值 慢性骨髓细胞白血病，PH1+急性淋巴细胞性白血病，慢性淋巴细胞性白血病，多个 骨髓瘤和HIV1/AIDS患者。第三个目标将验证新的预后价值 在一项多中心研究中，开发了HCT特异性合并症指数。几乎所有研究正在进行 在一个多机构财团的主持下，其中包括17个学术中心 西雅图，弗雷德·哈钦森癌症研究中心担任协调中心。 与公共卫生有关：这些拟议的研究旨在提高同种异体的安全性 HCT，每年已经用于治疗数千名患者的疗法。该项目的成功将扩大 同种异体HCT的应用大多是通过允许在老年患者和其他患者中的使用来应用 其他医疗问题。此外，所提出的方案允许最纯粹测定移植物。 肿瘤作用，除了强化条件外，还为添加的良好基础提供了良好的基础 疾病特定的方式。最后，合并症数据可能与定义癌症一样重要 诊断，阶段，缓解状态以及其他更熟悉的变量，以预测患者反应和 结果。