Intensification of Treosulfan-Fludarabine Conditioning With Thiotepa Exhibited Effectiveness and Tolerability in Older or Comorbid Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant With Active Myeloid Neoplasm: A Real-world Study

Background. – Reduced-intensity regimens such as treosulfan-fludarabine (TF) are currently considered cornerstones for older or comorbid patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) undergoing allogeneic hematopoietic stem cell transplant (alloSCT). However, data on its use in active disease cases are limited, and intensification strategies (such as thiotepa addition [TTF]) are not standardized in this setting. Methods. – To evaluate the efficacy and tolerability of treosulfan-based conditioning in the real-world setting and to provide insights into the use of thiotepa intensification, we retrospectively analyzed 66 (AML, n = 58; MDS, n = 8) patients transplanted between January 2016 and December 2023 at the Hematology Division of Udine, receiving TF (n = 48) or TTF (n = 18). Results. – At alloSCT, the median age was 67 y; 37 patients (56%) had a hematopoietic cell transplantation-comorbidity index of >2, and 13 (20%) had received previous alloSCT. Complete remission status was achieved by 52 (79%). A matched donor was used in 35 cases (53%). With a median follow-up of 16 mo, the cumulative incidences of 100-d grade ≥2 acute graft-versus-host disease and 3-y moderate-to-severe chronic graft-versus-host disease were 34% and 21%, respectively. After 3 y, cumulative incidences of nonrelapse mortality and disease relapse were 18% and 40%, with 46% progression-free survival and 52% overall survival. The TTF cohort included more cases with active disease status at alloSCT, both cytological (43% versus 12%, P = 0.005) and minimal residual disease positive (90% versus 40%, P = 0.005), compared with TF. Nevertheless, survival analysis confirmed no difference in nonrelapse mortality, progression-free survival, and overall survival among groups. Conclusions. – Our results confirmed the efficacy and tolerability of the TF regimen in older or comorbid AML and MDS patients in the real-world setting and suggest that double alkylation might counterbalance the adverse outcome risk posed by active disease at alloSCT. Furthermore, larger, prospective studies are needed to better elucidate the patients for whom the addition of thiotepa might be most beneficial.