Impact of Comorbidities on Outcomes of Allogeneic Transplantation

异基因造血细胞移植是一种治疗多种血液病的潜在疗法。 疾病。然而，许多可能从HCT中受益的患者没有资格享受 由于合并症和年龄所致的手术。随着降低强度养生法的发展和 清髓红细胞移植后支持性护理的改善，老年患者和 有同种异体血细胞移植的患者。我已经发表了第一份报告，描述了 合并症在预测HCT结局中的重要性。然后我继续开发了一种更敏感的新工具 评估异基因血细胞移植受者特有的合并症。红细胞压积特异性共病指数(HCTCI) 有助于更好地了解合并症对HCT结局的影响，并为此奠定了基础 求婚。这项建议的重点是进一步评估和发展合并症的预后价值。 以建立一个普遍适用的共病指数为最终目标。 在指导阶段，我收集了来自五个机构和 证实了HCT-CI的多中心效度。我也证明了年龄对 服用&gt；50年的患者中，非清髓的HCT结局，但死亡风险更高 清髓疗法。加权年龄间隔对HCT结果影响的分数被添加到 Hct-CI形成综合评分。这些研究的结果引导我进入《独立报》 这一阶段将涉及三个平行的主要目标。首先，我将测试结果预测的同质性Per 各机构的HCT-CI和HCT-CI/年龄预后评分预测效果的验证 在来自国际血液和骨髓移植中心的一个大型数据集(n=15,000)中 研究(CIBMTR)。第二，我将评估合并症对死因的生物学影响， 尤其是与急性移植物抗宿主病和器官衰竭以及生活质量有关的疾病 采用HCT-CI/AGE评分和个体共病负荷。这将涉及到双方 既往移植患者病历回顾及远期分析 包括更多患者的临床试验，并确保影响的预期重复性 合并症。第三，我将前瞻性地研究简化收集的三种不同方法 合并症数据，并制定一项教育方案，由数据登记员评估合并症， 因此，便于更广泛地纳入HCT中心的共病评估。

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for various hematological diseases. However, many patients who could potentially benefit from HCT have been ineligible for the procedure due to comorbidities and age. With the development of reduced-intensity regimens and improvements in supportive care after myeloablative HCT, increasing numbers of elderly patients and those with comorbidities have been offered allogeneic HCT. I have published the first report describing the importance of comorbidities in predicting HCT outcomes. I then went on to develop a more sensitive new tool to assess comorbidities specific for recipients of allogeneic HCT. The HCT-specific-comorbidity index (HCTCI) served to better understand the impact of comorbidities on HCT outcomes and it forms the basis for this proposal. This proposal is focused on further evaluating and developing the prognostic value of comorbidities for outcomes in HCT recipients with the eventual aim of creating a universally applicable comorbidity index. During the Mentored Phase, I have collected data from 3331 patients transplanted at five institutions and confirmed the multi-center validity of the HCT-CI. I also demonstrated lack of impact of age on nonmyeloablatlve HCT outcomes but higher risks for mortality among patients of >50 years given myeloablative regimens. Scores weighting the impact of age intervals on HCT outcomes were added to the HCT-CI to form composite scores. Results of these studies have guided me to proceed into the Independent Phase, which will address three parallel major aims. First, I will test homogeneity of outcome prediction per the HCT-CI across institutions and validation ofthe predictive impacts ofthe HCT-CI/age scores of outcomes in a large dataset (n=15,000) of patients from the Center of International Blood and Marrow Transplantation Research (CIBMTR). Second, I will assess the biological impact of comorbidities on causes of death, particularly those associated with acute graft-versus-host-disease and organ failures, and on quality of life after HCT using the HCT-CI/age scores as well as individual comorbidity burden. This will involve both retrospective reviews of medical records of previously transplanted patients and analyses of prospective clinical trials to include larger number of patients and to ensure prospective reproducibility of the impacts of comorbidities. Third, I will prospectively investigate three different methods for simplifying collection of comorbidity data and develop an educational program for evaluation of comorbidities by data registrars and, thereby, facilitate the more wide-spread incorporation of comorbidity assessment at HCT centers.