Poonsombudlert Kittika, Yodsuwan Ratdanai, Mott Sarah, Crawford Kathryn, Hornberg Sarah, Snow Anthony N, Sutamtewagul Grerk, Magalhaes-Silverman Margarida, Dhakal Prajwal
University of Iowa Health Care, Holden Comprehensive Cancer Center, Iowa City, Iowa, USA.
Eur J Haematol. 2025 Jul;115(1):29-35. doi: 10.1111/ejh.14415. Epub 2025 Mar 19.
NPM1 mutated AML without FLT3-ITD is considered "favorable" per the recent ELN 2022 criteria. However, our center has been challenged with treatment-refractory patients, prompting a search for additional prognostic factors.
We reviewed records of NPM1 AML patients from 2015 to 2024. Factors associated with event-free survival (EFS) and overall survival (OS) were evaluated using Cox regression.
Among 141 patients with NPM1 AML, subtype A was the most common (N = 99), followed by subtype D (N = 10), subtype B (N = 6), subtype G/I/J/K/R (N = 3/5/3/2/1) and other subtypes (N = 12). Ninety patients received chemotherapy (chemo), 41 received hypomethylating agent +/- venetoclax (HMA/ven) and 10 did not receive specific anti-AML therapy. At 12 months, EFS for subtypes A, D, B, G/I/J/K/R, and other subtypes were 49%, 58%, 50%, 49%, and 31%, and OS were 71%, 79%, 50%, 44%, and 56%, respectively. Fifty patients had allogeneic stem cell transplants: 33 in CR1 and 17 in CR2+. EFS at 12 months post-HSCT was 72%. On multivariable analysis, co-mutation with KRAS (HR: 2.69, 95% CI: 1.20-6.00) or TET2 (HR: 1.99, 95% CI: 1.22-3.26) was associated with worse EFS. For each 50 k/mm increase in WBC at diagnosis, the risk of relapse or death increased by 21%. For OS, co-mutation with IDH1/IDH2 (HR: 0.40, 95% CI: 0.21-0.74) was associated with better OS, whereas co-mutation with SRSF2 (HR: 2.70, 95% CI: 1.35-5.40) was associated with worse OS.
We did not find a statistically significant difference in EFS and OS among the NPM1 subtypes. However, our results showed that the prognoses of NPM1 AML can be influenced by other co-occurring mutations. A larger study is needed to confirm our findings.
根据最近的2022年欧洲白血病网络（ELN）标准，无FLT3-ITD突变的NPM1突变型急性髓系白血病（AML）被认为是“预后良好”的。然而，我们中心一直面临着治疗难治性患者的挑战，这促使我们寻找其他预后因素。
我们回顾了2015年至2024年NPM1 AML患者的记录。使用Cox回归评估与无事件生存期（EFS）和总生存期（OS）相关的因素。
在141例NPM1 AML患者中，A型是最常见的亚型（N = 99），其次是D型（N = 10）、B型（N = 6）、G/I/J/K/R型（N = 3/5/3/2/1）和其他亚型（N = 12）。90例患者接受了化疗（chemo），41例接受了去甲基化药物+/-维奈克拉（HMA/ven）治疗，10例未接受特定的抗AML治疗。在12个月时，A型、D型、B型、G/I/J/K/R型和其他亚型的EFS分别为49%、58%、50%、49%和31%，OS分别为71%、79%、50%、44%和56%。50例患者进行了异基因干细胞移植：33例在CR1期，17例在CR2+期。HSCT后12个月的EFS为72%。多变量分析显示，与KRAS（HR：2.69，95%CI：1.20-6.00）或TET2（HR：1.99，95%CI：1.22-3.26）共突变与较差的EFS相关。诊断时白细胞每增加50×10⁹/L，复发或死亡风险增加21%。对于OS，与IDH1/IDH2共突变（HR：0.40，95%CI：0.21-0.74）与较好的OS相关，而与SRSF2共突变（HR：2.70，95%CI：1.35-5.40）与较差的OS相关。
我们未发现NPM1各亚型之间在EFS和OS上有统计学显著差异。然而，我们的结果表明，NPM1 AML的预后可能受其他同时发生的突变影响。需要更大规模的研究来证实我们的发现。
