急性骨髓性白血病根據歐洲白血病研究網2022風險分類之預後分析與驗證：以18至65歲新診斷且接受標準引導化療的病人為族群

Abstract

急性骨髓性白血病為一複雜的惡性血液疾病。目前的治療主要根據歐洲白血病研究網提出之風險分類來進行。目前最常使用的為歐洲白血病研究網2017風險分類，其將病人分為「良好、中等、不良」，三種風險分類。然而，由於基因分析的進步與新的與預後相關的基因變化漸漸被發現，歐洲白血病研究網於2022年更新了風險分類準則，但是目前仍缺乏大型真實病人族群的驗證。 本研究以共809位、18至65歲新診斷且接受標準引導化療的急性骨髓性白血病病人為族群嘗試驗證歐洲白血病研究網2022風險分類。原先使用舊的歐洲白血病研究網2017風險分類的病人，在使用新的歐洲白血病研究網2022風險分類後，共106 (13.1%)位病人的分類有所改變。就存活率與疾病緩解率來看，歐洲白血病研究網2022風險分類能夠恰當的將病人分為良好、中等與不良，共三種風險。在接受標準引導化療後能達到完全緩解的病人之中，異體造血幹細胞移植能夠改善中等風險病人的預後，但是對於良好與不良兩種風險的病人沒有顯著幫助。 我們接著嘗試進一步改良歐洲白血病研究網2022風險分類。我們將良好風險之中的帶有染色體t(8;21)(q22;q22.1)/RUNX1::RUNX1T1變化合併KIThigh, JAK2或FLT3-ITDhigh基因突變的病人分類為中等風險、將中等風險之中的t(7;11)(p15;p15)/NUP98::HOXA9染色體變化以及DNMT3A合併FLT3-ITD基因突變的病人分類為不良風險、將不良風險中的complex or monosomal karyotypes、inv(3)(q21.3q26.2) or t(3 ;3)(q21.3 ;q26.2)/GATA2,MECOM(EVI1) 染色體變化或TP53基因突變分類為新增的「非常不良」風險。改良後的歐洲白血病研究網2022風險分類能夠恰當的將病人分為良好、中等、不良與非常不良，共四種風險。 綜上所述，歐洲白血病研究網2022風險分類能夠鑑別較年輕、接受標準引導化療的急性骨髓性白血病病人。由我們改良後的歐洲白血病研究網2022風險分類有機會能更加改善風險評估方式，而這需要日後大型前瞻性族群來驗證。

The European LeukemiaNet (ELN) recently proposed a revised recommendation for the diagnosis and management of acute myeloid leukemia (AML) in adults, recognized as ELN-2022. However, validation in a large real-world cohort remains lacking. In this study, we aimed to validate the prognostic relevance of the ELN-2022 in a cohort of 809 de novo, non-M3, younger (ages 18–65 years) AML patients receiving standard chemotherapy. The risk categories of 106 (13.1%) patients were reclassified from that determined using ELN-2017 to that determined using ELN-2022. The ELN-2022 effectively helped distinguish patients as favorable, intermediate, and adverse risk groups in terms of remission rates and survival. Among patients who achieved first complete remission (CR1), allogeneic transplantation was beneficial for those in the intermediate risk group, but not for those in the favorable or adverse risk groups. We further refined the ELN-2022 system by re-categorizing AML patients with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 with KIThigh, JAK2 or FLT3-ITDhigh mutations into the intermediate risk subset, AML patients with t(7;11)(p15;p15)/NUP98::HOXA9 and AML patients with co-mutated DNMT3A and FLT3-ITD into the adverse risk subsets, and AML patients with complex or monosomal karyotypes, inv(3)(q21.3q26.2) or t(3 ;3)(q21.3 ;q26.2)/GATA2,MECOM(EVI1) or TP53 mutation into the very adverse risk subset. The refined ELN-2022 system performed effectively to distinguish patients as favorable, intermediate, adverse and very adverse risk groups. In conclusion, the ELN-2022 helped distinguish younger, intensively treated patients into three groups with distinct outcomes; the proposed refinement of ELN-2022 may further improve risk stratification among AML patients. Prospective validation of the new predictive model is necessary.