Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial

作者：Matthias Stelljes, Jan Moritz Middeke, Gesine Bug, Eva Wagner-Drouet, Lutz Peter Mueller, Christoph Schmid, Stefan W. Krause, Wolfgang Bethge, Edgar Jost, Uwe Platzbecker, Stefan Klein, Judith Niederland, Martin Kaufmann, Kerstin Schäfer-Eckart, Henning Baldauf, Friedrich Stölzel, Sarah Trost, Christoph Röllig, Malte von Bonin, Katharina Egger‐Heidrich, Desireé Kunadt, Björn Steffen, Beate Hauptrock, Christoph Schliemann, Katja Sockel, Fabian Lang, Oliver Kriege, Judith Schaffrath, Christian Reicherts, Wolfgang E. Berdel, Hubert Serve, Gerhard Ehninger, Alexander H. Schmidt, Jan‐Henrik Mikesch, Martin Bornhäuser, Johannes Schetelig · 发表于：Blood · 年份：2025 · DOI：10.1182/blood.2025028730 · 被引用次数：11 · 研究领域：Acute Myeloid Leukemia Research、Hematopoietic Stem Cell Transplantation、Histone Deacetylase Inhibitors Research

ABSTRACT: Attempting to induce a complete remission before allogeneic hematopoietic cell transplant (alloHCT) is current practice in patients with acute myeloid leukemia (AML). However, benefit of remission induction strategy (RIST) before alloHCT has never been proven in a prospective trial. Potent conditioning regimens exist that allow for successful alloHCT in patients with active AML. Therefore, the ASAP trial was conducted to test RIST by salvage chemotherapy before alloHCT against immediate transplant after intensified conditioning. In total, 281 patients with AML with poor response after first induction or untreated first relapse were randomized 1:1 to RIST with high-dose cytarabine plus mitoxantrone vs immediate alloHCT with sequential conditioning after nonintensive disease control (DisC) measures, preferentially watchful waiting only. Overall survival at 5 years from randomization analyzed according to intention-to-treat was 46.1% for DisC vs 47.5% for RIST (P = .82). In multivariable Cox regression analysis, genetic AML risk according to European LeukemiaNet criteria (P < .0001), age (P = .001), and comorbidities (P = .046) predicted survival, but not treatment arm (hazard ratio, 1.08 for DisC vs RIST; P = .67). In conclusion, long-term follow-up of the ASAP trial showed no survival advantage for standard salvage chemotherapy before alloHCT as opposed to immediate alloHCT. The trial results question the general concept of RIST with intensive standard salvage therap...