Ong Shin Yeu, Tan Si Yun Melinda, Abdul Halim Nurul Aidah, Christopher Dheepa, Jen Wei Ying, Gallardo Christian, Tan Hwee Yim Angeline, Woon Yeow Kheong, Ng Heng Joo, Ooi Melissa, Wong Gee Chuan
Department of Haematology, Singapore General Hospital, Singapore 169856, Singapore.
Department of Haematology, Tan Tock Seng Hospital, Singapore 169856, Singapore.
Cancers (Basel). 2022 Jul 22;14(15):3576. doi: 10.3390/cancers14153576.
The prognostic value of measurable residual disease (MRD) by flow cytometry in acute myeloid leukemia (AML) patients treated with non-intensive therapy is relatively unexplored. The clinical value of MRD threshold below 0.1% is also unknown after non-intensive therapy. In this study, MRD to a sensitivity of 0.01% was analyzed in sixty-three patients in remission after azacitidine/venetoclax treatment. Multivariable cox regression analysis identified prognostic factors associated with cumulative incidence of relapse (CIR), progression-free survival (PFS) and overall survival (OS). Patients who achieved MRD < 0.1% had a lower relapse rate than those who were MRD ≥ 0.1% at 18 months (13% versus 57%, p = 0.006). Patients who achieved an MRD-negative CR had longer median PFS and OS (not reached and 26.5 months) than those who were MRD-positive (12.6 and 10.3 months, respectively). MRD < 0.1% was an independent predictor for CIR, PFS, and OS, after adjusting for European Leukemia Net (ELN) risk, complex karyotype, and transplant (HR 5.92, 95% CI 1.34−26.09, p = 0.019 for PFS; HR 2.60, 95% CI 1.02−6.63, p = 0.046 for OS). Only an MRD threshold of 0.1%, and not 0.01%, was predictive for OS. Our results validate the recommended ELN MRD cut-off of 0.1% to discriminate between patients with improved CIR, PFS, and OS after azacitidine/venetoclax therapy.
对于接受非强化治疗的急性髓系白血病（AML）患者，通过流式细胞术检测可测量残留病（MRD）的预后价值相对未被充分探索。非强化治疗后，MRD阈值低于0.1%的临床价值也尚不清楚。在本研究中，对63例接受阿扎胞苷/维奈克拉治疗后缓解的患者进行了灵敏度为0.01%的MRD分析。多变量cox回归分析确定了与复发累积发生率（CIR）、无进展生存期（PFS）和总生存期（OS）相关的预后因素。在18个月时，MRD<0.1%的患者复发率低于MRD≥0.1%的患者（13%对57%，p = 0.006）。达到MRD阴性完全缓解（CR）的患者中位PFS和OS（未达到和26.5个月）比MRD阳性患者更长（分别为12.6个月和10.3个月）。在调整欧洲白血病网（ELN）风险、复杂核型和移植因素后，MRD<0.1%是CIR、PFS和OS的独立预测因素（PFS的HR为5.92，95%CI为1.34−26.09，p = 0.019；OS的HR为2.60，95%CI为1.02−6.63，p = 0.046）。只有0.1%的MRD阈值，而不是0.01%，可预测OS。我们的结果验证了推荐的ELN MRD临界值0.1%可用于区分阿扎胞苷/维奈克拉治疗后CIR、PFS和OS改善的患者。
