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Publications

Journal Article Ahead of print

PubMed: 41609025 DOI: 10.3324/haematol.2025.288770

GVHD and GRFS in patients with acute myeloid leukemia undergoing allogeneic HCT with treosulfan- versus reduced-intensity busulfan-based conditioning: a subgroup analysis of a randomized phase 3 trial.

Haematologica

Authors: Friedrich Stölzel, Matthias Stelljes, Dietrich Wilhelm Beelen, Miroslaw Markiewicz, Péter Reményi, Thomas Luft, Fabio Ciceri, Eva-Maria Wagner-Drouet, Christian Junghanss, Christoph Scheid, Francesca Patriarca, Gerard Socié, Inken Hilgendorf, Alessandro Rambaldi, Kerstin Schaefer-Eckart, Domenico Russo, Gerald Wulf, Bertram Glass, Hélène Labussiere-Wallet, Gernot Stuhler, Maria Bieniaszewska, Jochen Casper, Ernst Holler, Fabio Benedetti, Anna Paola Iori, Desiree Kunadt, Jelena Mihajlović, Bettina Schild, Imran Khan, Xieran Li, Wolfgang Bethge

Affiliations

  • Division of Stem Cell Transplantation and Cellular Immunotherapy, University Hospital Schleswig-Holstein, Kiel, Christian Albrechts University, Kiel, Germany; Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Technical University Dresden.
  • Department of Medicine / Hematology and Oncology, University Hospital of Münster, Münster.
  • Department of Hematology and Stem Cell Transplantation, Faculty of Medicine and University Hospital Essen, University of Duisburg-Essen, Essen.
  • Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow.
  • Department of Hematology and Stem Cell Transplantation, St István and St László Hospital of Budapest, Budapest.
  • Department of Medicine, University of Heidelberg, Heidelberg.
  • Hematology and Bone Marrow Transplantation Unit, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan.
  • 3rd Department of Medicine - Hematology, University Medical Center, Mainz Germany.
  • Department of Hematology, Oncology and Palliative Care, University of Rostock.
  • Department I of Internal Medicine, University Hospital of Cologne, Cologne.
  • Hematological Clinic, University Hospital of Udine, Udine.
  • Hematology - BMT, Saint Louis Hospital, Paris.
  • Hematology and Oncology, University Hospital Jena, Jena.
  • Department of Oncology-Hematology, University of Milan and Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo.
  • Oncology, Hematology and Bone Marrow Transplantation, Klinikum Nürnberg, Campus Nord, Germany Paracelsus Medizinische Privat-Universität, Klinikum Nürnberg.
  • Unit of Blood Diseases and Bone Marrow Transplantation, ASST Spedali Civili Hospital, University of Brescia, Brescia.
  • Georg-August-University Göttingen, University Medicine Göttingen.
  • Department of Hematology, Asklepios Klinik St. Georg, Hamburg.
  • Department of Hematology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon.
  • Medizinische Klinik und Poliklinik II, Julius-Maximilians University, Würzburg.
  • Department of Hematology and Transplantology, Medical University of Gdańsk, Gdańsk.
  • University Clinic for Internal Medicine II - Oncology and Hematology, Clinic Oldenburg AöR, Oldenburg.
  • Department of Hematology and Oncology, Internal Medicine III, University Hospital of Regensburg, Regensburg.
  • Policlinic GB Rossi (Borgo Rome), Verona.
  • Policlinic Umberto I, University La Sapienza, Rome.
  • Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Technical University Dresden.
  • medac GmbH, Wedel.
  • Department of Hematology and Oncology, University of Tübingen, Tübingen.

Abstract

Acute myeloid leukemia (AML) is the most common indication for allogeneic hematopoietic cell transplantation (alloHCT), yet graft-versus-host disease (GVHD) remains a major post-transplant complication. Conditioning regimens, particularly reduced-intensity approaches, are critical in optimizing outcomes. This subgroup analysis of the phase 3 MC-FludT.14/L trial compared treosulfan-fludarabine with reduced-intensity busulfan-fludarabine in 352 AML patients (aged 31-70) undergoing alloHCT. The primary endpoint was 24-month event-free survival (EFS); secondary endpoints included overall survival (OS), GVHD incidence, relapse/progression, and non-relapse mortality (NRM). Treosulfan compared to busulfan demonstrated superiority: 24-month EFS was 65% vs. 53% (p = 0.01), and OS was 73% vs. 65%. EFS benefits were consistent across AML risk categories and notably higher in patients with hematopoietic cell transplantation comorbidity index >2 (62% vs. 42%, p = 0.02). Treosulfan also showed lower NRM and relapse rates. GVHD outcomes favored treosulfan, with a significantly lower incidence of extensive chronic GVHD at 24 months (15.1% vs. 28.1%, p = 0.01). GVHD-free and relapse-free survival was also improved (53% vs. 40%, p = 0.02). The safety profile was more favorable with treosulfan. These findings support treosulfan-fludarabine as a more effective and safer conditioning regimen than busulfan-fludarabine for AML patients undergoing alloHCT, particularly those at higher risk.

MeSH

Cells, Hematology, Incidence, Leukemia, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Transplants, Cell Transplantation, Conditioning, Psychological, Busulfan, Transplantation