Novel Strategies for Assessing and Optimizing Therapy for Minimal Residual Disease after Allogeneic Transplantation for AML and MDS

项目总结 异基因造血细胞移植(HCT)是一种重要的治疗手段，用于改善急性髓细胞白血病的预后。 急性髓系白血病(AML)和骨髓发育不良(MDS)患者。替代供体的研究进展 移植和支持性护理使更多的老年人和那些合并疾病的人能够 进行有可能治愈的移植手术。此外，靶向治疗的新兴时代允许 开发新的疾病缓解诱导方案以及移植调节方案，以增强 结果。然而，根据最近的数据，异基因HCT后的复发仍然是成功结果的主要障碍 这表明高达50%的同种异体红细胞移植失败和死亡与潜在疾病的持续或复发有关。 微小残留病(MRD)检测的最新进展提高了识别某些 HCT后有复发风险的患者。利用细胞遗传学、荧光原位杂交(FISH)获得的信息 和基因组学，仍然可以取得成功的结果，在部分骨髓恶性肿瘤患者移植到 移植时形态活动性疾病或MRD可检测疾病的设置。这项建议是一项试点研究，目的是 确定髓系恶性肿瘤移植前后的增强基因组MRD评估是否可以 用于指导临床研究人员提供HCT后治疗。通过这样做，我们希望确定两者的重要性 在HCT前后进行MRD，并开始探索使用各种细胞和/或 以药理学为目标的方法。

PROJECT SUMMARY Allogeneic hematopoietic cell transplantation (HCT) is an essential therapeutic procedure used to enhance the outcome of patients with acute myeloid leukemia (AML) and myelodysplasia (MDS). Recent advances in alternative donor transplantation and supportive care have allowed for a greater number of older adults and those with co-morbidities to pursue potentially curative transplant procedures. In addition, the emerging era of targeted therapy allows for the development of novel disease remission induction regimens as well as transplant conditioning regimens that can enhance outcomes. However, relapse after allogeneic HCT remains a major barrier to successful outcomes, with recent data suggesting that up to 50% of allogeneic HCT failure and mortality relate to persistence or relapse of underlying disease. Recent advances in the detection of minimal residual disease (MRD) have enhanced the capacity of identifying some patients at risk of relapse after HCT. Using information obtained by cytogenetics, fluorescence in situ hybridization (FISH) and genomics, successful outcomes can still be achieved in a subset of myeloid malignancy patients transplanted in the setting of morphologically active or MRD-detectable disease at the time of transplant. This proposal is a pilot study to determine whether augmented genomic MRD assessment both before and after transplant for myeloid malignancies can be used to guide clinical investigators into offering post-HCT therapy. In so doing we hope to establish the importance of both pre- and post-HCT MRD and to begin to explore novel interventions for post-HCT MRD using a variety of cellular and/or pharmacologic-targeted approaches.