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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Matthias Stelljes - , University Hospital Münster (Author)
  • Jan Moritz Middeke - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Gesine Bug - , University Hospital Frankfurt (Author)
  • Eva-Maria Wagner-Drouet - , University Medical Center Mainz (Author)
  • Lutz P Müller - , Martin Luther University Hospital (Author)
  • Christoph Schmid - , University Hospital Augsburg (Author)
  • Stefan W Krause - , University Hospital at the Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Wolfgang Bethge - , University Hospital Tübingen (Author)
  • Edgar Jost - , University Hospital Aachen (Author)
  • Uwe Platzbecker - , University Hospital Leipzig (Author)
  • Stefan A Klein - , Universitätsmedizin Mannheim (Author)
  • Judith Niederland - , HELIOS Klinikum Berlin-Buch (Author)
  • Martin Kaufmann - , Robert Bosch Krankenhaus Stuttgart (Author)
  • Kerstin Schäfer-Eckart - , Paracelsus Medical University Nuremberg, Nuremberg Clinic (Author)
  • Henning Baldauf - , DKMS Clinical Trials Unit (Author)
  • Friedrich Stölzel - , University Hospital Schleswig-Holstein Campus Kiel (Author)
  • Sarah Trost - , DKMS Clinical Trials Unit (Author)
  • Christoph Röllig - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Malte von Bonin - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Katharina Egger-Heidrich - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Desiree Kunadt - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Björn Steffen - , University Hospital Frankfurt (Author)
  • Beate Hauptrock - , University Medical Center Mainz (Author)
  • Christoph Schliemann - , University Hospital Münster (Author)
  • Katja Sockel - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Fabian Lang - , University Hospital Frankfurt (Author)
  • Oliver Kriege - , University Medical Center Mainz (Author)
  • Judith Schaffrath - , Martin Luther University Hospital (Author)
  • Christian Reicherts - , University Hospital Münster (Author)
  • Wolfgang E Berdel - , University Hospital Münster (Author)
  • Hubert Serve - , University Hospital Frankfurt (Author)
  • Gerhard Ehninger - , Cellex GmbH (Author)
  • Alexander H Schmidt - , DKMS Clinical Trials Unit (Author)
  • Jan-Henrik Mikesch - , University Hospital Münster (Author)
  • Martin Bornhäuser - , Department of Internal Medicine I, University Cancer Centre Dresden, University Hospital Carl Gustav Carus Dresden (Author)
  • Johannes Schetelig - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden, DKMS Clinical Trials Unit (Author)

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 therapy before alloHCT for all patients, because immediate alloHCT may reduce time in hospital and health care expenses. Novel bridging therapies that are well tolerated, and posttransplant maintenance with targeted drugs are urgently warranted, especially for adverse-risk AML, to improve outcomes after alloHCT. This trial was registered at www.ClinicalTrials.gov as #NCT02461537.

Details

Original languageEnglish
Pages (from-to)2293-2305
Number of pages13
JournalBlood
Volume146
Issue number19
Publication statusPublished - 6 Nov 2025
Peer-reviewedYes

External IDs

Scopus 105017672802

Keywords

Keywords

  • Humans, Leukemia, Myeloid, Acute/therapy, Female, Male, Middle Aged, Adult, Remission Induction, Hematopoietic Stem Cell Transplantation, Cytarabine/administration & dosage, Aged, Transplantation Conditioning/methods, Young Adult, Treatment Outcome, Adolescent, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Mitoxantrone/administration & dosage, Transplantation, Homologous, Follow-Up Studies, Salvage Therapy, Risk Factors