Vecchio Veronica, Duminuco Andrea, Leotta Salvatore, Mauro Elisa, Maugeri Cinzia, Parisi Marina, Fiumara Paolo Fabio, Di Raimondo Francesco, Palumbo Giuseppe A, Gozzo Lucia, Palumbo Fanny Erika, Vetro Calogero
Hematology Unit with BMT, A.O.U. Policlinico "G. Rodolico-San Marco", 95123 Catania, Italy.
Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.
J Clin Med. 2025 Jul 18;14(14):5110. doi: 10.3390/jcm14145110.
: Acute myeloid leukemia (AML) with internal tandem duplication (-ITD) mutations carries a poor prognosis. While inhibitors like midostaurin show benefits in combination with chemotherapy, the role of allelic ratio (AR), mutation status, and hematopoietic stem cell transplantation (HSCT) remains uncertain. Real-world data can help refine prognostic classification and treatment strategies. : We retrospectively analyzed 37 fit patients with -ITD AML treated with standard "7+3" chemotherapy, with and without midostaurin, between 2013 and 2022. Patients were stratified by -ITD AR, status, and treatment approach. Outcomes assessed included complete remission (CR), disease-free survival (DFS), and overall survival (OS). : Overall, 67.6% achieved CR/CRi. Response rates did not differ significantly by AR (low vs. high: 66.7% vs. 69.2%) or midostaurin use (72.6% vs. 60%; = 0.49). mutations were associated with improved DFS (10.3 vs. 3 months, = 0.036) but not OS. HSCT, performed in 54.1% of patients, mainly in first remission (CR1), significantly prolonged DFS (not reached vs. 5.3 months, = 0.005) and remained an independent predictor in multivariate analysis (HR: 0.160, = 0.039). OS (median 15.1 months) did not vary significantly across subgroups. Among patients achieving CR1, OS was significantly longer in those who underwent HSCT after midostaurin-based induction compared to those not transplanted (median OS not reached vs. 12.8 months; 95% CI, 6.9-18.7; = 0.045), whereas no significant benefit was observed after standard induction. In a landmark analysis restricted to patients transplanted in CR1, those who had received midostaurin-based induction showed a trend toward improved OS compared to those treated with standard induction (median OS not reached vs. 11.5 months; 95% CI, 0.5-25.0; = 0.086). : This real-life study supports the importance of mutations and HSCT in CR1, especially in the midostaurin era, for improving DFS in -ITD AML. These findings support updated guidelines for reducing the prognostic weight of AR and highlight the need for improved post-remission strategies in this setting.
伴有内部串联重复（-ITD）突变的急性髓系白血病（AML）预后较差。虽然像米哚妥林这样的抑制剂与化疗联合使用显示出益处，但等位基因比例（AR）、突变状态和造血干细胞移植（HSCT）的作用仍不确定。真实世界的数据有助于完善预后分类和治疗策略。我们回顾性分析了2013年至2022年间37例适合接受标准“7+3”化疗的-ITD AML患者，这些患者接受或未接受米哚妥林治疗。患者按-ITD AR、状态和治疗方法进行分层。评估的结局包括完全缓解（CR）、无病生存（DFS）和总生存（OS）。总体而言，67.6%的患者实现了CR/CRi。缓解率在AR（低 vs. 高：66.7% vs. 69.2%）或米哚妥林使用情况（72.6% vs. 60%；P = 0.49）方面无显著差异。 突变与DFS改善相关（10.3个月 vs. 3个月，P = 0.036）但与OS无关。54.1%的患者接受了HSCT，主要是在首次缓解期（CR1），显著延长了DFS（未达到 vs. 5.3个月，P = 0.005），并且在多变量分析中仍然是独立的预测因素（HR：0.160，P = 0.039）。OS（中位15.1个月）在各亚组间无显著差异。在达到CR1的患者中，与未接受移植的患者相比，在基于米哚妥林的诱导后接受HSCT的患者OS显著更长（中位OS未达到 vs. 12.8个月；95% CI，6.9 - 18.7；P = 0.045），而在标准诱导后未观察到显著益处。在一项仅限于在CR1期接受移植的患者的标志性分析中，与接受标准诱导治疗的患者相比，接受基于米哚妥林诱导治疗的患者显示出OS改善的趋势（中位OS未达到 vs. 11.5个月；95% CI，0.5 - 25.0；P = 0.086）。这项真实世界研究支持了 突变和CR1期HSCT在改善-ITD AML的DFS方面的重要性，特别是在米哚妥林时代。这些发现支持了降低AR预后权重的更新指南，并强调了在这种情况下改善缓解后策略的必要性。
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