Comparison of Fludarabine/Treosulfan Conditioning with Melphalan-Based Sequential Conditioning in Patients with MDS and Increased Blasts Undergoing Upfront Transplantation
- 1Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany
Abstract
Background: Upfront allogeneic stem cell transplantation (allo-SCT) without pretransplant cytoreduction is an established concept in patients with myelodysplastic syndromes with increased blasts (MDS-IB), but the optimal conditioning strategy remains to be defined. While fludarabine and treosulfan (Flu/Treo) has become an established regimen for older patients based on its favorable ratio between toxicity and efficacy, its impact when used in the context of upfront transplant is less well described. Methods: Here, we retrospectively investigated Flu/Treo as the backbone for conditioning in 35 patients with MDS-IB (median blast count 13%) receiving upfront transplantation. Results: Outcomes in this high-risk cohort (75% IPSS-M high or very high) were promising, with an estimated 2-year overall (OS), relapse-free survival (RFS) and non-relapse mortality (NRM) of 76%, 56% and 13%, respectively. Relapse was the major cause of treatment failure, reflected by a relapse incidence (CIR) of 31%. We identified the TP53 mutation status as the main driver of relapse (2-year RFS TP53 mutated 17% vs. 67%, p = 0.01; 2-year CIR 54% vs. 24%, p = 0.08) and an adverse prognostic factor, while the pretransplant blast count did not affect the post-transplant outcome. Intensification with the addition of melphalan (Mel, n = 18) to a sequential conditioning approach did not improve the outcome (Mel vs. Flu/Treo 2-year OS 62% vs. 87%, RFS 50% vs. 63%, CIR 37% vs. 24%, NRM 14% vs. 12%, all not significant). Conclusions: This pilot series shows that upfront transplantation using Flu/Treo conditioning in high-risk MDS patients facilitates promising post-transplant outcomes and may serve as a backbone to further improve these results through innovative peri-transplant interventions.
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BibTeX
@article{metzdorf2026comparison,
title = {{Comparison of Fludarabine/Treosulfan Conditioning with Melphalan-Based Sequential Conditioning in Patients with MDS and Increased Blasts Undergoing Upfront Transplantation}},
author = {Judith Metzdorf and Artur Schneider and Jacob Pyka and Annemarie Mohring and Jennifer Kaivers and Tim Lohmann and Hans Christian Reinhardt and Nicolaus Kröger and Christina Rautenberg and Thomas Schroeder},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203303},
url = {https://www.mdpi.com/2072-6694/18/20/3303},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparison of Fludarabine/Treosulfan Conditioning with Melphalan-Based Sequential Conditioning in Patients with MDS and Increased Blasts Undergoing Upfront Transplantation
AU - Judith Metzdorf
AU - Artur Schneider
AU - Jacob Pyka
AU - Annemarie Mohring
AU - Jennifer Kaivers
AU - Tim Lohmann
AU - Hans Christian Reinhardt
AU - Nicolaus Kröger
AU - Christina Rautenberg
AU - Thomas Schroeder
PY - 2026
DA - 2026/10/14
JO - Cancers
DO - 10.3390/cancers18203303
UR - https://www.mdpi.com/2072-6694/18/20/3303
AB - Background: Upfront allogeneic stem cell transplantation (allo-SCT) without pretransplant cytoreduction is an established concept in patients with myelodysplastic syndromes with increased blasts (MDS-IB), but the optimal conditioning strategy remains to be defined. While fludarabine and treosulfan (Flu/Treo) has become an established regimen for older patients based on its favorable ratio between toxicity and efficacy, its impact when used in the context of upfront transplant is less well described. Methods: Here, we retrospectively investigated Flu/Treo as the backbone for conditioning in 35 patients with MDS-IB (median blast count 13%) receiving upfront transplantation. Results: Outcomes in this high-risk cohort (75% IPSS-M high or very high) were promising, with an estimated 2-year overall (OS), relapse-free survival (RFS) and non-relapse mortality (NRM) of 76%, 56% and 13%, respectively. Relapse was the major cause of treatment failure, reflected by a relapse incidence (CIR) of 31%. We identified the TP53 mutation status as the main driver of relapse (2-year RFS TP53 mutated 17% vs. 67%, p = 0.01; 2-year CIR 54% vs. 24%, p = 0.08) and an adverse prognostic factor, while the pretransplant blast count did not affect the post-transplant outcome. Intensification with the addition of melphalan (Mel, n = 18) to a sequential conditioning approach did not improve the outcome (Mel vs. Flu/Treo 2-year OS 62% vs. 87%, RFS 50% vs. 63%, CIR 37% vs. 24%, NRM 14% vs. 12%, all not significant). Conclusions: This pilot series shows that upfront transplantation using Flu/Treo conditioning in high-risk MDS patients facilitates promising post-transplant outcomes and may serve as a backbone to further improve these results through innovative peri-transplant interventions.
SN - 2072-6694
ER -