Sobas Marta Anna, Turki Amin T, Ramiro Angela Villaverde, Hernández-Sánchez Alberto, Elicegui Javier Martinez, González Teresa, Melchor Raúl Azibeiro, Abáigar María, Tur Laura, Dall'Olio Daniele, Sträng Eric, Tettero Jesse M, Castellani Gastone, Benner Axel, Döhner Konstanze, Thiede Christian, Metzeler Klaus H, Haferlach Torsten, Damm Frederik, Ayala Rosa, Martínez-López Joaquín, Mills Ken I, Sierra Jorge, Lehmann Sören, Porta Matteo G Della, Mayer Jiri, Reinhardt Dirk, Medina Rubén Villoria, Schulze-Rath Renate, Barbus Martje, Hernández-Rivas Jesús María, Huntly Brian J P, Ossenkoppele Gert, Döhner Hartmut, Bullinger Lars
Department of Hematology, Blood Neoplasm and Bone Marrow Transplantation, Wroclaw Medical University.
Department of Hematology and Oncology, Marienhospital University Hospital, Ruhr-University Bochum, Bochum.
Haematologica. 2025 May 1;110(5):1126-1140. doi: 10.3324/haematol.2024.285805. Epub 2024 Nov 7.
Since 2017, targeted therapies combined with conventional intensive chemotherapy have started to improve outcomes of patients with acute myeloid leukemia (AML). However, even before these innovations, outcomes with intensive chemotherapy had improved, which has not yet been extensively studied. Thus, we used a large pan-European multicenter dataset of the HARMONY Alliance to evaluate treatment-time dependent outcomes over two decades. In 5,359 AML patients, we compared the impact of intensive induction therapy on outcome over four consecutive 5-year calendar periods from 1997 to 2016. During that time, the 5-year survival of AML patients improved significantly, also across different genetic risk groups. In particular, the 60-day mortality rate dropped from 13.0% to 4.7% over time. The independent effect of calendar periods on outcome was confirmed in multivariate models. Improvements were documented both for patients <60 and ≥60 years old, and in those treated with and without consolidating allogeneic hematopoietic stem cell transplantation (alloHCT). While survival of AML elderly patients remains poor, patients ≥60 years old overall have a 20% survival benefit at 5 years if they receive an alloHCT. While further outcome improvement in intensively treated AML patients will likely be driven by targeted treatment approaches, this pan-European HARMONY dataset can serve as a multicenter comparator for future studies.
自2017年以来，靶向治疗与传统强化化疗相结合已开始改善急性髓系白血病（AML）患者的预后。然而，甚至在这些创新疗法出现之前，强化化疗的预后就已经有所改善，但这一点尚未得到广泛研究。因此，我们使用了HARMONY联盟的一个大型泛欧洲多中心数据集来评估二十多年来治疗时间依赖性的预后情况。在5359例AML患者中，我们比较了1997年至2016年连续四个5年日历期内强化诱导治疗对预后的影响。在此期间，AML患者的5年生存率显著提高，不同遗传风险组均如此。特别是，60天死亡率随时间从13.0%降至4.7%。多变量模型证实了日历期对预后的独立影响。年龄＜60岁和≥60岁的患者，以及接受和未接受巩固性异基因造血干细胞移植（alloHCT）的患者，其预后均有改善。虽然AML老年患者的生存率仍然很低，但≥60岁的患者如果接受alloHCT，总体上5年生存率有20%的获益。虽然强化治疗的AML患者预后的进一步改善可能将由靶向治疗方法推动，但这个泛欧洲的HARMONY数据集可作为未来研究的多中心对照。
