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

评估和优化 AML 和 MDS 异基因移植后微小残留病治疗的新策略

基本信息

批准号：
10434659
负责人：
RICHARD Thomas MAZIARZ
金额：
$ 18.66万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-27 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10434659
关键词：
Acute Lymphocytic Leukemia Acute Myelocytic Leukemia Address Allogenic Area Azacitidine Biology Blood Blood Cells Bone Marrow Cell Therapy Cessation of life Chimerism Clinical Clinical Investigator Clinical Trials Network Collaborations Cytogenetics DNA sequencing Data Decitabine Detection of Minimal Residual Disease Development Disease Disease remission Donor Lymphocyte Infusion Donor person Dysmyelopoietic Syndromes Early Diagnosis Educational workshop Effectiveness Elderly Failure Flow Cytometry Fluorescent in Situ Hybridization Genomics Homologous Transplantation Immunity Immunosuppression In complete remission Infrastructure Infusion procedures Institutes Institution International Intervention Investigation Leadership Literature Maintenance Therapy Malignant Neoplasms Marrow Measurement Methods Molecular Molecular Cytogenetics Morphology Multicenter Studies Mutation Myelogenous Myeloproliferative disease Natural Killer Cells Outcome Patient-Focused Outcomes Patients Pharmacology Pilot Projects Polymerase Chain Reaction Prevention Preventive therapy Procedures Prognostic Factor Recurrent disease Regimen Relapse Remission Induction Reporting Research Residual Neoplasm Role Salvage Therapy Site Stem cell transplant Supportive care Survival Rate T-Lymphocyte Technology Tetrahydrouridine Therapeutic procedure Time Transplant Recipients Transplantation Transplantation Conditioning Treatment Failure Umbilical Cord Blood Valproic Acid Withdrawal burden of illness chemotherapy cohort comorbidity conditioning detection method experience hematopoietic cell transplantation high risk immune reconstitution improved improved outcome meetings member mortality next generation novel novel strategies novel therapeutics participant enrollment phase 2 study post intervention post-transplant post-transplant disease prevent prognostic prognostic significance relapse risk sequencing platform standard measure targeted treatment transplantation therapy treatment optimization

项目摘要

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.

项目摘要异基因造血细胞移植（HCT）是一种重要的治疗程序，用于提高造血干细胞移植的结果。急性髓性白血病（AML）和骨髓增生异常（MDS）患者。替代供体的最新进展移植和支持性护理使更多的老年人和患有合并症的人能够寻求潜在的治愈性移植手术。此外，新兴的靶向治疗时代允许开发新的疾病缓解诱导方案以及移植预处理方案，结果。然而，最近的数据显示，同种异体HCT后复发仍然是成功结局的主要障碍，提示高达50%的同种异体HCT失败和死亡率与潜在疾病的持续或复发有关。最近在微小残留病（MRD）检测方面的进展提高了识别某些肿瘤的能力， HCT后有复发风险的患者。利用细胞遗传学、荧光原位杂交（FISH）和基因组学，成功的结果仍然可以在骨髓恶性肿瘤患者的一个子集中实现移植，在移植时存在形态学活性或MRD可检测的疾病。这项建议是一项试验性研究，确定是否可以在骨髓恶性肿瘤移植前后进行增强的基因组MRD评估，用于指导临床研究者提供HCT后治疗。我们希望通过这样做来确立两者的重要性 HCT前和HCT后MRD，并开始探索使用各种细胞和/或药理学靶向方法。