Publication Full Title: A phase II multicenter prospective study to evaluate the safety and efficacy of myeloablative-dose treosulfan plus fludarabine (FT14) conditioning regimen in allogeneic hematopoietic stem cell transplantation for AML patients aged 40–65 in first complete remission
Journal: Bone Marrow Transplantation
Published: 24 June 2026
Publication Link: https://www.nature.com/articles/s41409-026-02937-7
Commented by: Prof. Daniele Avenoso, Associate Professor and Dr. Paolo Clementi, haematology trainee, University of Brescia and ASST Spedali Civili di Brescia, Italy.
Summary
This prospective multicenter phase II study evaluated the safety and efficacy of a fully myeloablative conditioning regimen based on treosulfan (14 g/m² for three days) plus fludarabine (FT14) in 82 patients aged 40–65 years with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation in first complete remission. The trial was designed to assess whether FT14 could provide outcomes comparable to the current standard myeloablative fludarabine-busulfan (FB4) regimen while reducing transplant-related toxicity.
The primary endpoint, 1-year leukemia-free survival (LFS), was successfully met. One-year LFS reached 81.7%, while overall survival was 90.2%. The cumulative incidence of relapse was 14.9% at one year, whereas non-relapse mortality remained remarkably low at only 3.7%. Importantly, no cases of primary graft failure, septic death, or hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) were observed. Engraftment was universal and infectious complications, although common, were never fatal. Acute grade II-IV graft-versus-host disease occurred in 12% of patients and chronic GVHD in approximately 7%, resulting in a favorable one-year GVHD-free/relapse-free survival of 74.4%.
Overall, the study suggests that FT14 combines robust anti-leukemic activity with a particularly favorable toxicity profile, supporting its use as an alternative myeloablative platform, especially in patients for whom busulfan-related toxicity is a major concern. The authors conclude that randomized studies directly comparing FT14 with FB4 are now warranted.
Comment
This study addresses one of the most relevant challenges in modern transplantation: preserving the anti-leukemic efficacy of myeloablative conditioning while reducing regimen-related toxicity. As the transplant population becomes progressively older and medically more complex, conditioning intensity is no longer simply a question of disease control but also of biological tolerability.
The prospective design deserves particular attention. Most evidence supporting myeloablative treosulfan has originated from retrospective registry analyses or indirect comparisons. Here, the investigators provide prospective data confirming what many transplant physicians have increasingly suspected in clinical practice: treosulfan can achieve true myeloablation without reproducing the organ toxicity traditionally associated with busulfan.
Perhaps the most striking observation is not the leukemia-free survival itself-which is certainly encouraging-but the exceptionally low transplant-related mortality. A one-year non-relapse mortality below 4%, combined with the complete absence of VOD/SOS, graft failure and infection-related deaths, represents an outcome that would have been difficult to imagine with conventional myeloablative regimens only a decade ago. These findings reinforce the concept that "myeloablative" and "high toxicity" no longer have to be synonymous.
Equally interesting is the low incidence of both acute and chronic GVHD (with ATG-based prophylaxis) despite maintaining effective disease control. Although the study cannot establish causality, the reduced mucosal toxicity associated with treosulfan may contribute to limiting inflammatory tissue damage and, consequently, the initiation of alloreactive responses. This hypothesis deserves further mechanistic investigation. Some limitations should nevertheless be acknowledged. The trial is a single-arm phase II study using historical controls rather than a randomized comparison. Furthermore, longer observation will be required to determine whether the excellent early safety profile translates into durable disease control. Overall, this study strengthens the growing body of evidence supporting treosulfan as more than simply a reduced-toxicity alternative. It may represent a genuine evolution of myeloablative conditioning, capable of expanding access to transplantation while maintaining curative potential. The logical next step is a randomized head-to-head comparison against contemporary busulfan-based platforms to determine whether treosulfan should become a new standard for fit AML patients undergoing allogeneic transplantation.