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Background <p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes in patients with acute myeloid leukemia (AML) harboring <i>FLT3</i>-internal tandem duplication (<i>FLT3-ITD</i>) mutations. However, relapse still occurs in 15–35% of these patients after transplantation. Therefore, early and highly sensitive detection methods are required to identify patients at risk of relapse and enable timely post-transplant intervention.</p> Methods <p>In this NICHE cohort study, a total of 136 patients were included, then we evaluated whether high-sensitivity polymerase chain reaction (PCR)-next-generation sequencing (NGS) for <i>FLT3-ITD</i> (limit of detection: 5 × 10<sup>−6</sup>) on day + 30 post-HSCT could identify patients at a high risk of relapse and inform decisions regarding maintenance therapy.</p> Results <p>Among the 136 patients, 37 patients (27.2%) had detectable <i>FLT3-ITD</i> clones on day + 30. These patients exhibited a significantly higher cumulative incidence of post-HSCT multiparameter flow cytometry (MFC)-measurable residual disease (MRD) relapse (40.3% vs. 18.8%, <i>p</i> = 0.001). Notably, <i>FLT3-ITD</i>–positive patients who received <i>FLT3</i> inhibitor maintenance therapy had no relapses, while 6 out of the 13 patients who did not receive maintenance therapy relapsed. Conversely, <i>FLT3-ITD</i>–negative patients without high-risk factors (2022 European LeukemiaNet adverse-risk group, relapsed/refractory AML, MFC-MRD positivity pre-HSCT) showed limited benefit from maintenance therapy (MFC-MRD–free survival: hazard ratio (HR) = 0.25 (0.03–2.11), <i>p</i> = 0.204; OS: HR = 0.20 (0.02–1.70), <i>p</i> = 0.142).</p> Conclusions <p>This is the first study to demonstrate that detection of minimal <i>FLT3-ITD</i> clones at the fixed time point of day + 30 post-HSCT can reliably stratify relapse risk in AML patients and provide a rationale for individualized post-transplant maintenance therapy.</p>

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Day + 30 detection of minimal residual FLT3-ITD by high-sensitivity PCR-NGS predicts relapse risk and guides post-transplant maintenance in AML

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月3日

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  • Shan Jiang,
  • Dan Feng,
  • Li Wan,
  • Nan Yang,
  • Jiao Ma,
  • Jiaxin Cao,
  • Pan Pan,
  • Yawei Zheng,
  • Yigeng Cao,
  • Wenbin Cao,
  • Chen Liang,
  • Xin Chen,
  • Rongli Zhang,
  • Qiaoling Ma,
  • Jialin Wei,
  • Weihua Zhai,
  • Donglin Yang,
  • Yi He,
  • Sizhou Feng,
  • Mingzhe Han,
  • Yao Yao,
  • Aiming Pang,
  • Erlie Jiang

摘要

Background

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes in patients with acute myeloid leukemia (AML) harboring FLT3-internal tandem duplication (FLT3-ITD) mutations. However, relapse still occurs in 15–35% of these patients after transplantation. Therefore, early and highly sensitive detection methods are required to identify patients at risk of relapse and enable timely post-transplant intervention.

Methods

In this NICHE cohort study, a total of 136 patients were included, then we evaluated whether high-sensitivity polymerase chain reaction (PCR)-next-generation sequencing (NGS) for FLT3-ITD (limit of detection: 5 × 10−6) on day + 30 post-HSCT could identify patients at a high risk of relapse and inform decisions regarding maintenance therapy.

Results

Among the 136 patients, 37 patients (27.2%) had detectable FLT3-ITD clones on day + 30. These patients exhibited a significantly higher cumulative incidence of post-HSCT multiparameter flow cytometry (MFC)-measurable residual disease (MRD) relapse (40.3% vs. 18.8%, p = 0.001). Notably, FLT3-ITD–positive patients who received FLT3 inhibitor maintenance therapy had no relapses, while 6 out of the 13 patients who did not receive maintenance therapy relapsed. Conversely, FLT3-ITD–negative patients without high-risk factors (2022 European LeukemiaNet adverse-risk group, relapsed/refractory AML, MFC-MRD positivity pre-HSCT) showed limited benefit from maintenance therapy (MFC-MRD–free survival: hazard ratio (HR) = 0.25 (0.03–2.11), p = 0.204; OS: HR = 0.20 (0.02–1.70), p = 0.142).

Conclusions

This is the first study to demonstrate that detection of minimal FLT3-ITD clones at the fixed time point of day + 30 post-HSCT can reliably stratify relapse risk in AML patients and provide a rationale for individualized post-transplant maintenance therapy.