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

• 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
• 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

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 同种异性造血细胞移植（HCT）是一种基本的治疗方法，用于增强结果 患有急性髓样白血病（AML）和骨髓增生（MDS）的患者。替代捐助者的最新进展 移植和支持护理允许更多的老年人和有合并症的老年人 采用潜在的治愈性移植程序。此外，有针对性疗法的新兴时代允许 新型疾病缓解诱导方案以及可以增强的移植调节方案的发展 结果。但是，同种异体HCT后的复发仍然是成功结果的主要障碍 表明多达50％的同种异体HCT衰竭和死亡率与潜在疾病的持久性或复发有关。 检测最小残留疾病（MRD）的最新进展增强了鉴定的能力 HCT后有复发风险的患者。使用通过细胞遗传学获得的信息，原位杂交（FISH） 和基因组学，成功的结果仍然可以在移植到 移植时的形态活性或MRD可检测疾病的设置。该建议是一项试点研究 确定在移植前后的基因组MRD评估是否可以是 用于指导临床研究人员提供HCT疗法。这样我们希望确定两者的重要性 HCT前后MRD，并开始使用各种细胞和/或 靶向药理学方法。

项目成果

Post-allogeneic stem cell transplant FLT3- targeted maintenance therapy: updates and considerations for clinical practice.

• DOI: 10.46439/stemcell.3.015
• 发表时间: 2022
• 期刊: Archives of stem cell and therapy
• 作者: Cohen J;Maziarz RT
• 通讯作者: Maziarz RT