Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA.
Bone Marrow Transplant. 2021 Dec;56(12):3091-3093. doi: 10.1038/s41409-021-01475-8. Epub 2021 Sep 28.
Measurable residual disease (MRD) is associated with poor prognosis in acute myeloid leukemia (AML), even after allogeneic hematopoietic cell transplantation (HCT). New next-generation sequencing (NGS) methods have emerged as a highly sensitive and specific method to detect MRD. In addition to defining the role of post-HCT MRD monitoring in FLT3-ITD mutated AML, there is great interest in the optimal use of oral FLT3 tyrosine kinase inhibitors (FLT3 inhibitors) to maintain remission following HCT. In this study, we evaluated the clinical impact of sensitive FLT3 MRD testing early after HCT and maintenance FLT3 inhibitor use at our transplant center. We found that there was a trend towards inferior progression-free survival (PFS) for patients with early post-HCT MRD, but that overall survival (OS) was not significantly impacted by MRD. The use of maintenance FLT3 inhibitors led to a significantly superior PFS and OS in our cohort, and improved PFS and OS in both MRD-negative and MRD-positive patients. Altogether, our results demonstrate the prognostic significance of NGS-based MRD monitoring for FLT3-ITD and the ability of post-HCT maintenance therapy to prevent relapse and death in FLT3-ITD mutated AML.
可测量残留疾病 (MRD) 与急性髓系白血病 (AML) 的预后不良相关,即使在异基因造血细胞移植 (HCT) 后也是如此。新的下一代测序 (NGS) 方法已成为一种高度敏感和特异的检测 MRD 的方法。除了定义移植后 MRD 监测在 FLT3-ITD 突变 AML 中的作用外,人们对最佳使用口服 FLT3 酪氨酸激酶抑制剂 (FLT3 抑制剂) 以维持 HCT 后缓解也非常感兴趣。在这项研究中,我们评估了我们移植中心在 HCT 后早期进行敏感的 FLT3 MRD 检测和维持 FLT3 抑制剂使用的临床影响。我们发现,HCT 后早期 MRD 患者的无进展生存期 (PFS) 有下降趋势,但 MRD 对总生存期 (OS) 没有显著影响。在我们的队列中,使用维持性 FLT3 抑制剂可显著改善 PFS 和 OS,并且在 MRD 阴性和 MRD 阳性患者中均改善了 PFS 和 OS。总之,我们的结果表明,基于 NGS 的 MRD 监测对 FLT3-ITD 具有预后意义,以及移植后维持治疗能够预防 FLT3-ITD 突变 AML 的复发和死亡。