文章：

成人急性髓系白血病患者合并KMT2A重排的结局预测因素

Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements

原文发布日期：2021-09-29

DOI: 10.1038/s41408-021-00557-6

类型: Article

开放获取: 是

英文摘要：

Acute myeloid leukemia (AML) with rearrangement of the lysine methyltransferase 2a gene (KMT2Ar) has adverse outcomes. However, reports on the prognostic impact of various translocations causing KMT2Ar are conflicting. Less is known about associated mutations and their prognostic impact. In a retrospective analysis, we identified 172 adult patients with KMT2Ar AML and compared them to 522 age-matched patients with diploid AML. KMT2Ar AML had fewer mutations, most commonly affecting RAS and FLT3 without significant impact on prognosis, except for patients with ≥2 mutations with lower overall survival (OS). KMT2Ar AML had worse outcomes compared with diploid AML when newly diagnosed and at relapse, especially following second salvage (median OS of 2.4 vs 4.8 months, P < 0.0001). Therapy-related KMT2Ar AML (t-AML) had worse outcomes compared with de novo KMT2Ar AML (median OS of 0.7 years vs 1.4 years, P < 0.0001). Allogeneic hematopoietic stem cell transplant (allo-HSCT) in first remission was associated with improved OS (5-year, 52 vs 14% for no allo-HSCT, P < 0.0001). In a multivariate analysis, translocation subtypes causing KMT2Ar did not predict survival, unlike age and allo-HSCT. In conclusion, KMT2Ar was associated with adverse outcomes regardless of translocation subtype. Therefore, AML risk stratification guidelines should include all KMT2Ar as adverse.
 

摘要翻译： 

赖氨酸甲基转移酶2a基因重排（KMT2Ar）的急性髓系白血病（AML）预后不良。然而，关于导致KMT2Ar的不同易位对预后影响的报告存在矛盾。对其相关突变及其预后影响的了解较少。在一项回顾性分析中，我们确定了172例成人KMT2Ar AML患者，并将其与522例年龄匹配的二倍体AML患者进行了比较。KMT2Ar AML的突变较少，最常见的是影响RAS和FLT3基因的突变，除了≥2个突变患者的总生存期（OS）较低外，这些突变对预后无显著影响。与二倍体AML相比，KMT2Ar AML在新诊断和复发时，尤其是在第二次挽救治疗后（中位OS为2.4个月 vs 4.8个月，P＜0.0001）的预后更差。与原发性KMT2Ar AML相比，治疗相关的KMT2Ar AML（t-AML）预后更差（中位OS为0.7年 vs 1.4年，P＜0.0001）。首次缓解期进行异基因造血干细胞移植（allo-HSCT）与改善OS相关（5年OS为52% vs 未移植组的14%，P＜0.0001）。在多变量分析中，与年龄和allo-HSCT不同，导致KMT2Ar的易位亚型不能预测生存率。总之，无论易位亚型如何，KMT2Ar均与不良预后相关。因此，AML风险分层指南应将所有KMT2Ar列为不良预后因素。

原文链接：

Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements