Transplantation and cellular therapy · 2026
Fludarabine-Treosulfan (FT10) Conditioning in Older AML Patients Undergoing Haploidentical Transplantation: A Prospective Italian Study With External Comparison to the Haplo-UK Reduced-Intensity Conditioning Cohort.
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Federico Vincenzo, Avenoso Daniele, Raj Kavita, De Lavallade Hugues, Wilson William, Matera Rosella, Salvatore Dalila, Canale Filippo A, Merla Manuela, Contento Corine, Campagna Giulia, Renzo Giuseppe Di, Vaddinelli Doriana, Natale Annalisa, Seripa Davide, Grassi Tiziana, Saraceni Francesco, Santarone Stella, Carella Angelo M, Russo Domenico, Milano Filippo, Martino Massimo, Renzo Nicola Di
Аннотация
BACKGROUND: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains the only curative strategy for high-risk acute myeloid leukemia (AML), but its applicability in elderly and comorbid patients is limited by conditioning-related toxicity. Haploidentical HSCT (haplo-HSCT) with post-transplant cyclophosphamide (PTCy) has expanded access to transplantation, yet the optimal reduced-intensity conditioning (RIC) regimen in this setting remains undefined. Treosulfan-based conditioning combined with fludarabine (FT10) has demonstrated a favourable toxicity profile in matched donor transplantation, but prospective data in the haploidentical platform are scarce.
METHODS: We conducted a prospective, multicentre feasibility study across eight transplant centres, enrolling patients with intermediate- or high-risk AML (ELN-2017), aged ≥65 years, with haematopoietic cell transplantation-comorbidity index (HCT-CI) ≥2, lacking an HLA-identical donor and undergoing FT10-based haplo-HSCT between June 2019 and December 2023. Conditioning consisted of treosulfan (30 g/m²) and fludarabine (150 mg/m²), followed by GVHD prophylaxis with PTCy, cyclosporine and mycophenolate mofetil. Primary endpoint was cumulative incidence of nonrelapse mortality (NRM). Transplant outcomes were descriptively compared with an external reduced-intensity conditioning cohort from the prospective phase II Haplo-UK study.
RESULTS: Thirty-five AML patients were included in the FT10 cohort (median age 69 years); 58% were transplanted in complete remission (CR) with negative MRD, 22% in CR with positive MRD and 20% with active disease. Median neutrophil and platelet engraftment occurred at days +14 and +22, respectively, with full donor chimerism achieved in 94% of evaluable patients and one case of graft failure (2.8%). Cumulative incidence of NRM was 18% at day +100 and 28% at 1 year, with infections representing the leading cause of nonrelapse death. Outcomes were strongly influenced by disease status at transplant: 1-year OS and LFS were 79% and 70% in patients transplanted in CR/MRD-negative, compared with 42% and 38% in those transplanted with active disease. Acute grade II-IV and chronic GVHD occurred in 13% and 40% of patients, respectively. When restricted to patients transplanted in CR, survival and relapse outcomes were broadly comparable to those observed in the Haplo-UK cohort, despite the substantially older age and higher comorbidity burden of FT10 patients.
CONCLUSIONS: In this prospective, real-world multicentre study, FT10-based haploidentical HSCT with PTCy proved feasible and effective in elderly, comorbid AML patients. These findings suggest that FT10 represents a viable conditioning option for a highly vulnerable population traditionally excluded from transplant and support further validation in larger comparative studies.
METHODS: We conducted a prospective, multicentre feasibility study across eight transplant centres, enrolling patients with intermediate- or high-risk AML (ELN-2017), aged ≥65 years, with haematopoietic cell transplantation-comorbidity index (HCT-CI) ≥2, lacking an HLA-identical donor and undergoing FT10-based haplo-HSCT between June 2019 and December 2023. Conditioning consisted of treosulfan (30 g/m²) and fludarabine (150 mg/m²), followed by GVHD prophylaxis with PTCy, cyclosporine and mycophenolate mofetil. Primary endpoint was cumulative incidence of nonrelapse mortality (NRM). Transplant outcomes were descriptively compared with an external reduced-intensity conditioning cohort from the prospective phase II Haplo-UK study.
RESULTS: Thirty-five AML patients were included in the FT10 cohort (median age 69 years); 58% were transplanted in complete remission (CR) with negative MRD, 22% in CR with positive MRD and 20% with active disease. Median neutrophil and platelet engraftment occurred at days +14 and +22, respectively, with full donor chimerism achieved in 94% of evaluable patients and one case of graft failure (2.8%). Cumulative incidence of NRM was 18% at day +100 and 28% at 1 year, with infections representing the leading cause of nonrelapse death. Outcomes were strongly influenced by disease status at transplant: 1-year OS and LFS were 79% and 70% in patients transplanted in CR/MRD-negative, compared with 42% and 38% in those transplanted with active disease. Acute grade II-IV and chronic GVHD occurred in 13% and 40% of patients, respectively. When restricted to patients transplanted in CR, survival and relapse outcomes were broadly comparable to those observed in the Haplo-UK cohort, despite the substantially older age and higher comorbidity burden of FT10 patients.
CONCLUSIONS: In this prospective, real-world multicentre study, FT10-based haploidentical HSCT with PTCy proved feasible and effective in elderly, comorbid AML patients. These findings suggest that FT10 represents a viable conditioning option for a highly vulnerable population traditionally excluded from transplant and support further validation in larger comparative studies.