Novel Intervention Approaches to Alleviate Allogeneic Transplant-Related Morbidity and Mortality

项目摘要/摘要 背景：血液系统恶性肿瘤是一种罕见的影响血液和淋巴系统的癌症。 只有通过移植供体干细胞，即异基因造血细胞才能治愈 移植(HCT)。虽然进步改善了年轻人和其他健康的人的结果 HCT对老年人和老年人的健康相关生活质量(HRQOL)具有破坏性影响 患有HM的病体虚弱(脆弱)的患者。我们是第一个开发出Hct特异性共病指数的人。 (HCT-CI)，特别表明那些高分的人在 与合并症较低的患者相比，HCT后的HRQOL和更高的发病率和死亡率 得分。在我们和其他人的初步研究的指导下，我们建议在这里随机选择那些脆弱的患者 在支持性和姑息性护理之间，针对特定并发症的临床管理，这两种方法 综合和标准护理(SOC)，看看哪种干预措施可以改善这些患者术后的HRQOL HCT。目标：(1)在随机第二阶段研究中评估四种方法的有效性 在改善异基因红细胞移植易感受者的90天HRQOL中提到的上述；(2)在 第三阶段研究第二阶段的获胜者是否与SOC相比确实改善了HRQOL；以及(3)比较 关于生存、患者报告的其他结果和资源使用的干预措施。 方法：我们将在五个大型移植中进行一项多中心无缝II/III期随机临床试验。 中锋。无缝功能意味着第二阶段分析中使用的患者将包括在第三阶段中 分析，但只有在第二阶段产生的干预措施明显优于SOC的情况下，才会发生这种情况。在AIM 我们将招募年龄为≥65岁、Hct-CI评分为≥3和/或步行速度较慢的患者 作为虚弱的迹象，在他们开始异基因红细胞移植的两周前。每个介入臂都将是 在10周内实施，在HCT之前2周和之后8周，以在以下方面实现最大好处 为患者做好接受HCT的准备，并指导他们完成程序的早期阶段。病人将会是 随机分配给上述四只手臂中的一只。如果有来自第二阶段的干预手臂 改善HRQOL，然后我们将继续在第三阶段研究中仅针对SOC测试该ARM。我们只会 第三阶段需要额外300名弱势患者(第二/第三阶段总共600人)。在目标3中，我们将看到是否有 这些干预措施可以改善存活率、患者报告的其他结果和/或资源的使用。 患者结局：这项建议首次比较了这些围移植期干预措施对易感人群的影响 HM患者接受HCT治疗。结果可以将痛苦降到最低，如果可能，还可以延长类似患者的生命。 在未来和世界范围内。结果还可能鼓励医生为更脆弱的人提供移植 患者，由于担心其发病率和死亡风险，目前被拒绝接受这一手术。最后， 国家对医疗资源的总体利用可以得到改善，以造福于其他患者。

Project Summary/Abstract BACKGROUND: Hematological malignancies (HM) are rare cancers that affect the blood and lymph system and can only be cured with transplantation of donor stem cells; namely allogeneic hematopoietic cell transplantation (HCT). While advancements have improved outcomes for younger and otherwise healthy patients, HCT can have devastating effects on the health-related quality of life (HRQOL) for older and medically infirm (vulnerable) patients with HM. We were the first to develop an HCT-specific comorbidity index (HCT-CI) that specifically showed that those with high scores can suffer from significant impairments in HRQOL and higher rates of morbidity and mortality after HCT compared to patients with lower comorbidity scores. Guided by our and others’ preliminary studies, we propose here to randomize those vulnerable patients between supportive and palliative care, clinical management targeting specific comorbidities, both approaches combined, vs. standard of care (SOC) to see which intervention can improve HRQOL of those patients after HCT. OBJECTIVES: (1) Evaluate in a randomized phase II study the effectiveness of the four approaches mentioned above in improving day-90 HRQOL for vulnerable recipients of allogeneic HCT; (2) determine in a phase III study whether the winner arm from phase II definitively improves HRQOL vs. SOC; and (3) compare the interventions with respect to survival, additional patient-reported outcomes, and the use of resources. METHODS: We will conduct a multi-center seamless phase II/III randomized clinical trial in five large transplant centers. The seamless feature means patients used in the phase II analysis will be included in the phase III analysis but that will only happen if phase II produces an intervention with a clear advantage over SOC. In Aim 1, we will enroll 300 patients who either have age of ≥65 years, HCT-CI scores of ≥3, and/or slow walk speed as indication of frailty, two weeks before they start their allogeneic HCT. Each intervention arm will be implemented over 10 weeks period, 2 weeks before and 8 weeks after HCT, to achieve the maximum benefit in preparing patients for HCT and guiding them through the early phases of the procedure. Patients will be randomly assigned to one of the four arms described above. If there is an intervention arm from phase II that improves HRQOL, then we will continue to test that arm only against SOC in a phase III study. We will only need an additional 300 vulnerable patients for phase III (total of 600 for phase II/III). In Aim 3, we will see if any of the interventions can improve survival, other patient-reported outcomes, and/or the use of resources. PATIENT OUTCOMES: This proposal is the first to compare these peri-transplant interventions in vulnerable HM patients given HCT. Results can minimize the suffering and, if possible, prolong the lives of similar patients in the future and world-wide. Results could also encourage physicians to offer transplants to more vulnerable patients, who are currently being denied the procedure for fear of its morbidity and mortality risks. Finally, the national overall use of healthcare resources could be improved for the benefit of other patients.