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

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.

Authors

Institutions

Publication Details

Journal
Haematologica
Published
2026-01-29
DOI
https://doi.org/10.3324/haematol.2025.288770
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Imran Khan, Gerald Wulf, Eva Wagner-Drouet, Fabio Ciceri et al.
Haematologica
Hematopoietic Stem Cell Transplantation
article

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

Imran Khan, Gerald Wulf, Eva Wagner-Drouet, Fabio Ciceri, Inken Hilgendorf, Friedrich Stölzel, Desireé Kunadt, Christoph Scheid, Kerstin Schaefer-Eckart, Fabio Benedetti, Maria Bieniaszewska, Gernot Stuhler, Xieran Li, G. Socié, Bertram Glass, Beelen Dw, Ernst Holler, Jochen Casper, Péter Reményi, Anna Paola Iori, Francesca Patriarca, Jelena Mihajlović, Bettina Schild, Matthias Stelljes, Alessandro Rambaldi, Miroslaw Markiewicz, Domenico Russo, Thomas Luft
article en

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.

Haematologica
University of Verona (IT), University of Udine (IT), Carl von Ossietzky Universität Oldenburg (DE), Johannes Gutenberg University Mainz (DE), Heidelberg University (DE), University of Würzburg (DE), Policlinico Umberto I (IT), Saint Louis University Hospital (US), Brescia University (US), University Hospital Regensburg (DE), Christian-Albrechts-Universität zu Kiel (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), Nuremberg Hospital (DE), Hospices Civils de Lyon (FR), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), University Hospital Münster (DE), Ospedale Papa Giovanni XXIII (IT), Klinikum Oldenburg (DE), Hôpital Lyon Sud (FR), Paracelsus Medizinische Privatuniversität (DE), Unified Szent István and Szent László Hospital (HU), Essen University Hospital (DE), Asklepios Klinik St. Georg (DE), Jena University Hospital (DE), Hôpital Saint-Louis (FR), Klinik und Poliklinik für Kinder- und Jugendpsychiatrie (DE), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University Hospital Cologne (DE), University Hospital Carl Gustav Carus (DE), Medac (Germany) (DE), University of Rostock (DE), University of Duisburg-Essen (DE), University of Göttingen (DE), Gdańsk Medical University (PL), University of Tübingen (DE), University of Rzeszów (PL)
Medac
Good health and well-being
Openalex Percentile: Top 76%
Hematopoietic Stem Cell Transplantation
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.