Fludarabine-treosulfan compared with fludarabine-melphalan conditioning for adult acute lymphoblastic leukemia.

The optimal conditioning strategy for adult acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains undefined, particularly in older or medically vulnerable patients. Reduced-intensity regimens lower non-relapse mortality (NRM) but increase relapse risk. Treosulfan-based conditioning may represent an intermediate-intensity alternative, though comparative data in ALL are limited. We conducted a retrospective registry-based study including 967 adult patients with B- or T-ALL undergoing first allo-HSCT in complete remission (CR1 or CR2+) between 2012 and 2024. Patients received fludarabine-melphalan (Flu/Mel, n=778) or fludarabine-treosulfan (Flu/Treo, n=189). The primary endpoint was leukemia-free survival (LFS); secondary endpoints included overall survival (OS), relapse incidence (RI), NRM, and graft-versus-host disease. Outcomes were censored at 2 years. Multivariable Cox models adjusted for clinical and transplant-related variables. Flu/Treo recipients were transplanted more recently, more often received haploidentical donors, and were more frequently beyond CR1. Median age was slightly higher in the Flu/Treo group. At 2 years, OS was 65.6% with Flu/Treo versus 60.5% with Flu/Mel, and LFS 57.2% versus 49.7%. RI was lower with Flu/Treo (24.1% vs 31.5%), while NRM was similar (18.6% vs 18.8%). In multivariable analysis, conditioning regimen did not significantly affect OS or LFS, but Flu/Treo was associated with reduced RI (HR 0.61, p=0.011) without differences in NRM. Similar results were observed in B-ALL, while no differences emerged in T-ALL. Flu/Treo was associated with a lower relapse incidence compared with Flu/Mel, particularly in patients with B-cell ALL, without an increase in non-relapse mortality. However, no significant differences were observed in overall survival or leukemia-free survival. These findings support Flu/Treo as a reasonable alternative conditioning platform for adult patients with ALL and warrant prospective validation.

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Publication Details

Journal
Blood Advances
Published
2026-10-28
DOI
https://doi.org/10.1182/bloodadvances.2026021035
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
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article

Fludarabine-treosulfan compared with fludarabine-melphalan conditioning for adult acute lymphoblastic leukemia.

Kavita K Raj, Éolia Brissot, Mohamad Mohty, Fabio Ciceri et al.
Blood Advances
Hematopoietic Stem Cell Transplantation
article

Fludarabine-treosulfan compared with fludarabine-melphalan conditioning for adult acute lymphoblastic leukemia.

Kavita K Raj, Éolia Brissot, Mohamad Mohty, Fabio Ciceri, Allain-Thibeault Le Sourd Ferhat, Mirko Farina, Victoria T. Potter, Michele Malagola, Matthew P. Collin, Rachel Elizabeth Protheroe, Arnon Nagler, Kate Stringaris, Daniele Avenoso, Jenny Byrne, Ángela Maria Trujillo, Emma Nicholson, Deborah Susan Richardson, Mohamed Houhou, Harpreet Kaur, JENNIFER C. CLAY, Sridhar Chaganti, Muhammad Saif, Andrew D Clark
article en

Abstract

The optimal conditioning strategy for adult acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains undefined, particularly in older or medically vulnerable patients. Reduced-intensity regimens lower non-relapse mortality (NRM) but increase relapse risk. Treosulfan-based conditioning may represent an intermediate-intensity alternative, though comparative data in ALL are limited. We conducted a retrospective registry-based study including 967 adult patients with B- or T-ALL undergoing first allo-HSCT in complete remission (CR1 or CR2+) between 2012 and 2024. Patients received fludarabine-melphalan (Flu/Mel, n=778) or fludarabine-treosulfan (Flu/Treo, n=189). The primary endpoint was leukemia-free survival (LFS); secondary endpoints included overall survival (OS), relapse incidence (RI), NRM, and graft-versus-host disease. Outcomes were censored at 2 years. Multivariable Cox models adjusted for clinical and transplant-related variables. Flu/Treo recipients were transplanted more recently, more often received haploidentical donors, and were more frequently beyond CR1. Median age was slightly higher in the Flu/Treo group. At 2 years, OS was 65.6% with Flu/Treo versus 60.5% with Flu/Mel, and LFS 57.2% versus 49.7%. RI was lower with Flu/Treo (24.1% vs 31.5%), while NRM was similar (18.6% vs 18.8%). In multivariable analysis, conditioning regimen did not significantly affect OS or LFS, but Flu/Treo was associated with reduced RI (HR 0.61, p=0.011) without differences in NRM. Similar results were observed in B-ALL, while no differences emerged in T-ALL. Flu/Treo was associated with a lower relapse incidence compared with Flu/Mel, particularly in patients with B-cell ALL, without an increase in non-relapse mortality. However, no significant differences were observed in overall survival or leukemia-free survival. These findings support Flu/Treo as a reasonable alternative conditioning platform for adult patients with ALL and warrant prospective validation.

Blood Advances
University Hospitals Birmingham NHS Foundation Trust (GB), Royal Marsden NHS Foundation Trust (GB), Nottingham University Hospitals NHS Trust (GB), University College London Hospitals NHS Foundation Trust (GB), Inserm (FR), Leeds Teaching Hospitals NHS Trust (GB), Sheba Medical Center (IL), University Hospital Southampton NHS Foundation Trust (GB), Clatterbridge Cancer Centre NHS Foundation Trust (GB), Sorbonne Université (FR), Assistance Publique – Hôpitaux de Paris (FR), Sheffield Teaching Hospitals NHS Foundation Trust (GB), Hôpital Saint-Antoine (FR), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Royal Marsden Hospital (GB), IRCCS Ospedale San Raffaele (IT), King's College Hospital (GB), Queen Elizabeth University Hospital (GB), European Society for Blood and Marrow Transplantation (FR), Bristol NHS Foundation Trust (GB), University College London (GB), University of Brescia (IT), Newcastle University (GB)
Openalex Percentile: Top 11%
Hematopoietic Stem Cell Transplantation
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