A Retrospective Cohort Study of FLT3 Turnaround Time in Acute Myeloid Leukemia (AML) Patients and the Clonal Evolution of FLT3 in Relapse/Refractory AML Patients in National Taiwan University Hospital
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,213
- 试验地点
- 1
- 主要终点
- Estimate FLT3 testing turnaround time in clinical practice.
研究概览
简要总结
This retrospective cohort study aims to describe the current FLT3 testing landscape in Taiwan. It includes two patient groups: non-M3 primary AML patients with relapsed/refractory disease (R/R cohort) and newly diagnosed non-M3 primary AML patients (newly diagnosed cohort).
Primary objectives:
Estimate FLT3 testing turnaround time in clinical practice. Assess FLT3 clonal evolution in the R/R cohort.
Secondary objectives:
Determine FLT3 mutation prevalence. Describe karyotypes, co-mutations, and allelic ratios in both cohorts. Study European LeukemiaNet (ELN) risk in the newly diagnosed cohort. Evaluate the association of FLT3 mutation changes with treatment discontinuation and overall survival (OS) in the R/R cohort.
Investigate the link between Measurable Residual Disease (MRD) outcomes with treatment discontinuation and OS in the newly diagnosed cohort.
Data from the National Taiwan University Hospital integrated Medical Database (NTUH-iMD) and NTUH-AML dataset will be used. The index date is the earliest R/R AML evidence for the R/R cohort and the initial AML diagnosis date for the newly diagnosed cohort. A three-year baseline period will provide patient history and comorbidity information. Patients will be followed until the study's end, loss to follow-up, or death.
详细描述
Acute myeloid leukemia (AML) is a heterogeneous group of hematological diseases. According to the Taiwan Cancer Registry Annual Report, 859 new AML cases were diagnosed in Taiwan in 2018, with an age-standardized incidence rate of 3.06 in males and 2.18 in females per 100,000 person-years.
The FMS-like tyrosine kinase 3 gene (FLT3) affects the proliferation and differentiation of stem cells or hematopoietic progenitor cells. FLT3 mutations are found in 25-30% of newly diagnosed AML patients and are considered a negative prognostic factor, remaining significant even after intensive chemotherapy and/or stem cell transplant.
Two critical issues for ensuring timely targeted therapy for FLT3+ patients are the speed of FLT3 test turnaround and the use of tests at key time points. Rapid turnaround times are necessary for early intervention, with European LeukemiaNet (ELN) recommending results within 3 days. However, it's unclear if this is achievable in real-world settings. FLT3 mutation status evolves, with 15-25% of patients losing and 13% acquiring the mutation at relapse. Despite guidelines recommending FLT3 testing at diagnosis and relapse, there is no consensus in Taiwan on its importance and timing.
Some observational studies on AML in Taiwan have been conducted but provide limited information on the timing and turnaround of FLT3 testing in real-world practice.
This study will describe the current FLT3 testing landscape, including turnaround time and timing of tests among adult relapsed/refractory (R/R) AML patients at NTUH. It will also investigate the clinical characteristics and survival outcomes of both adult R/R AML and newly diagnosed AML patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed/refractory cohort:
- •Adult patient (age ≥18 years) diagnosed with non-M3 primary AML (confirmed diagnosis using WHO 2016 criteria within the NTUH-AML dataset) who:
- •First experienced refractory disease (failure to achieve complete remission or complete remission with incomplete hematologic recovery) to 2 cycles of induction therapy between 1 January 2009 and 31 December 2019, OR
- •First experienced hematological relapse after a CR between 1 January 2009 and 31 December
- •Patient with bone marrow blasts ≥5 %, reappearance of blasts in the blood, or development of extramedullary disease after achieving remission is defined to have relapse of AML.
- •Newly diagnosed cohort:
- •Adult patient (age ≥ 18 years) newly diagnosed with non-M3 primary AML (confirmed diagnosis using WHO 2016 criteria within the NTUH-AML dataset) between 1 January 2009 and 31 December 2019.
排除标准
- •Relapsed/refractory cohort:
- •Patient with M3 subtype (acute promyelocytic leukemia, APL)
- •Patient with prior history of myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN)
- •Patient without any FLT3 records
- •Patient with secondary or therapy-related AML
- •Newly diagnosed cohort:
- •Patient with M3 subtype (APL)
- •Patient with prior history of MDS or MPN
- •Patient without any FLT3 records
- •Patient with secondary or therapy-related AML
结局指标
主要结局
Estimate FLT3 testing turnaround time in clinical practice.
时间窗: From date of diagnosis until the date of death from any cause, assessed up to 30 years
This outcome measure focuses on determining the average time required to complete FLT3 testing from the point of sample collection to the delivery of results in a real-world clinical setting. The goal is to evaluate the efficiency and speed of the current FLT3 testing processes. By estimating the turnaround time, the investigators aim to identify potential delays and areas for improvement to ensure timely initiation of targeted therapies for patients with acute myeloid leukemia (AML). This data will provide valuable insights into the operational aspects of FLT3 testing and its alignment with clinical practice guidelines.
Assess FLT3 clonal evolution in the relapsed/refractory cohort.
时间窗: From date of diagnosis until the date of death from any cause, assessed up to 30 years
This outcome measure involves analyzing the changes in FLT3 mutation status in patients with relapsed or refractory acute myeloid leukemia (AML). The study aims to track the presence, loss, or acquisition of FLT3 mutations over the course of the disease. By examining FLT3 clonal evolution, the investigators aim to better understand how these genetic changes correlate with disease progression, treatment response, and overall patient outcomes. The results will provide insights into the dynamics of FLT3 mutations and inform future therapeutic strategies.
次要结局
- Determine FLT3 mutation prevalence at diagnosis(From date of diagnosis until the date of death from any cause, assessed up to 30 years)
- Evaluate the association of FLT3 mutation changes with treatment discontinuation and overall survival (OS) in the relapsed/refractory cohort.(From date of diagnosis until the date of death from any cause, assessed up to 30 years)
- Investigate the link between Measurable Residual Disease (MRD) outcomes with treatment discontinuation and OS in the newly diagnosed cohort.(From date of diagnosis until the date of death from any cause, assessed up to 30 years)
研究者
National Taiwan University Clinical Trial Center
National Taiwan University Hospital
National Taiwan University Hospital