Droplet digital PCR improves measurable residual disease detection and predicts relapse in KMT2A-rearranged leukemia after allogeneic hematopoietic stem cell transplantation: A prospective study

作者：Ya Luo, Ya‐Zhen Qin, Xiaosu Zhao, Ying‐Jun Chang, Jing Liu, Xiao‐Dong Mo, Yuqian Sun, Yu Wang, Lanping Xu, Xiaohui Zhang, Xiaojun Huang, Meng Lv · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-3518 · 被引用次数：1 · 研究领域：Acute Myeloid Leukemia Research、Innovative Microfluidic and Catalytic Techniques Innovation、Hematopoietic Stem Cell Transplantation

Abstract Background: KMT2A-rearranged (KMT2A-r) leukemia represents a high-risk subtype marked by aggressive biology and high early relapse risk. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is commonly used for remission consolidation. Our prior work showed that detectable KMT2A transcripts by real-time quantitative PCR (RT-qPCR) before HSCT was associated with inferior 3-year outcomes: OS (51% vs. 82%, p < .001), LFS (42% vs. 81%, p < .001), and CIR (33% vs. 12%, p < .001) (Cancer, 2025). Post-HSCT, KMT2A transcript–positive patients experienced poor outcomes: relapse rate 93.5%, 3-year OS 12.5%, and LFS 0% (Br J Haematol, 2025; BBMT, 2014). Notably, 77.8% of transcript reappearance occurred within 3–4 months post-HSCT, with a median interval of 109 days (range, 44–305) from re-positivity to relapse. Given this high relapse risk, whether droplet digital PCR (ddPCR)—with greater sensitivity and absolute quantification—can improve MRD monitoring and relapse prediction remains unknown. Methods In this prospective trial (NCT06211166), we enrolled patients with KMT2A-r acute leukemia undergoing allo-HSCT. Serial MRD monitoring was performed post-HSCT using both RT-qPCR and ddPCR targeting patient-specific KMT2A fusion transcripts. Patients were categorized into three cohorts based on longitudinal MRD results: (1) Double-negative (DN): persistently negative by both assays; (2) Discordant (Dis): persistently RT-PCR–negative but with ≥1 ddPCR-...