Abstract：
Juvenile myelomonocytic leukaemia (JMML) is a rare myeloproliferative neoplasm requiring haematopoietic stem cell transplantation (HSCT) for potential cure. Relapse poses a significant obstacle to JMML HSCT treatment, as the lack of effective minimal residual disease (MRD)-monitoring methods leads to delayed interventions. This retrospective study utilized the droplet digital PCR (ddPCR) technique, a highly sensitive nucleic acid detection and quantification technique, to monitor MRD in 32 JMML patients. The results demonstrated that ddPCR detected relapse manifestations earlier than traditional methods and uncovered molecular insights into JMML MRD dynamics. The findings emphasized a critical 1- to 3-month window post-HSCT for detecting molecular relapse, with 66.7% (8/12) of relapses occurring within this period. Slow MRD clearance post-HSCT was observed, as 65% (13/20) of non-relapse patients took over 6 months to achieve ddPCR-MRD negativity. Furthermore, bone marrow ddPCR-MRD levels at 1-month post-HSCT proved to be prognostically significant. Relapsed patients exhibited significantly elevated ddPCR-MRD levels at this time point (p = 0.026), with a cut-off of 0.465% effectively stratifying overall survival (p = 0.007), event-free survival (p = 0.035) and cumulative incidence of relapse (p = 0.035). In conclusion, this study underscored ddPCR\'s superiority in JMML MRD monitoring post-HSCT. It provided valuable insights into JMML MRD dynamics, offering guidance for the effective management of JMML.
摘要：
幼年型粒单核细胞白血病（JMML）是一种罕见的骨髓增殖性肿瘤，需要造血干细胞移植（HSCT）才能治愈。复发对JMMLHSCT治疗构成重大障碍，由于缺乏有效的微小残留病（MRD）监测方法导致延迟干预。这项回顾性研究利用了液滴数字PCR(ddPCR)技术，一种高灵敏度的核酸检测和定量技术，监测32例JMML患者的MRD。结果表明，ddPCR比传统方法更早地检测到复发表现，并揭示了对JMMLMRD动力学的分子见解。研究结果强调了HSCT后检测分子复发的关键1至3个月窗口，66.7%(8/12)的复发发生在这一时期。观察到HSCT后MRD清除缓慢，因为65%(13/20)的非复发患者需要6个月以上才能达到ddPCR-MRD阴性.此外，HSCT后1个月的骨髓ddPCR-MRD水平被证明具有预后意义。复发患者在该时间点表现出显著升高的ddPCR-MRD水平(p=0.026),截断率为0.465%，可有效分层总生存率(p=0.007)，无事件生存率(p=0.035)和累积复发率(p=0.035).总之,这项研究强调了ddPCR在HSCT后JMMLMRD监测中的优越性。它提供了对JMMLMRD动态的宝贵见解，为JMML的有效管理提供指导。
