Long-Term Safety and Efficacy of Treosulfan-Based Conditioning Regimens of Allogeneic Hematopoietic Cell Transplantation

Background: Treosulfan-based regimens have been widely used, with outcomes comparable to other myeloablative conditionings, even in older or frail patients. However, the long-term safety and efficacy of these regimens remain unknown.

Methods: We prospectively studied consecutive patients that received allogeneic hematopoietic cell transplantation (alloHCT) in our JACIE-accredited center over the last decade with the conditioning regimen of FT14 (Fludarabine 150mg/m²-Treosulfan 42mg/m²). Post-transplant Cyclophosphamide was added in haploidentical donors and ATG (Thymoglobulin 5mg/kg) in patients with unrelated donors. The following factors were studied: age, type of disease/donor/graft, phase at transplant, CD34 cells infused, infections, cumulative incidence/CI of graft-versus-host disease (GVHD) and treatment-related mortality (TRM), overall (OS) and disease-free survival (DFS).

Results: We studied 186 patients, with a median age of 59 (18-70) years, transplanted with FT14 due to de novo and secondary acute myeloid leukemia (80 and 30 patients respectively), myelodysplastic syndrome (46), and myeloproliferative neoplasm (30). The majority (89) was transplanted in first complete remission/CR, while 62 in second CR, and 35 in refractory/relapsed disease. Grafts were peripheral blood stem cells from matched/mismatched unrelated (90/23), sibling (59) and haploidentical (12) donors. Median time of hospitalization in the BMT unit was 18 (14-29) days. Median time to neutrophil engraftment was 10 (8-13) days and to platelet engraftment 12 (9-55) days. Only 6 patients (3.2%) presented with grade 3 diarrhea. No other severe adverse events were related to the conditioning regimen.

Full donor chimerism was achieved in all patients at median 31 (14-92) post-transplant days. We calculated acceptable rates of CI in acute (gr 2-4) GVHD (37,6%) and moderate/severe chronic GVHD (30.6%). Disease relapse was observed in 47/186 (25.3%) patients. With a median follow-up of 16.3 (1.5-84.5) months, 5-year DFS and OS were 49% and 71% respectively, in all patients, while in patients transplanted in CR1 DFS and OS were 59% and 75.8% respectively. Disease relapse (p<0.001) and gr 2-4 acute GVHD (p=0.001) predicted poor OS in the multivariate analysis, independently of disease phase in transplant. Five-year CI of TRM was 15,3 %, independently predicted by grade 2-4 acute GVHD (p=0.003).

Conclusion: Our real-world study confirms that alloHCT with treosulfan-based regimens is safe and effective in a wide range of myeloid neoplasms, expanding the population eligible for transplantation. Therefore, the choice of alloHCT in this patient population needs to be personalized.