Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome using treosulfan based compared to other reduced‐intensity or myeloablative conditioning regimens. A report of the chronic malignancies working party of the EBMT

Abstract

Allogeneic haematopoietic-cell transplantation (allo-HCT) is a potentially curative therapy for high-risk myelodysplastic syndrome (MDS). Reducedintensity conditioning (RIC) is usually associated with lower non-relapse mortality (NRM), higher relapse rate and similar overall-survival (OS) as myeloablative-conditioning (MAC). Fludarabine/treosulfan (FT) is a reduced-toxicity regimen with intense anti-leukaemia activity and a favourable toxicity profile. We investigated post-transplant outcomes in 1722 MDS patients following allo-HCT with FT (n = 367), RIC (n = 687) or MAC (n = 668). FT and RIC recipients were older than MAC recipients, median age 59, 59 and 51 years, respectively (P < 0Á001) but other disease characteristics were similar. The median follow-up was 64 months (1-171). Five-year relapse rates were 25% (21-30), 38% (34-42) and 25% (22-29), after FT, RIC and MAC, respectively, (P < 0Á001). NRM was 30% (25-35), 27% (23-30) and 34% (31-38, P = 0Á008), respectively. Five-year OS was 50% (44-55), 43% (38-47), and 43% (39-47), respectively (P = 0Á03). In multivariate analysis, FT was associated with a lower risk of relapse (HR 0Á55, P < 0Á001) and better OS (HR 0Á72, P = 0Á01). MAC was associated with higher NRM (HR 1Á44, P = 0Á001). In conclusion, FT is associated with similar low relapse rates as MAC and similar low NRM as RIC, resulting in improved OS. FT may be the preferred regimen for allo-HCT in MDS.

What’s Next after Hypomethylating Agents Failure in Myeloid Neoplasms? A Rational Approach

“…In addition, early studies suggested that a high-intensity myeloablative conditioning (MAC) regimen should be considered whenever clinically suitable as the risk of MDS relapse after Allo-HCT in the HMA-exposed is higher in patients who receive lower-intensity conditioning (HR 1.81, 95% CI 1.07–3.06, p = 0.03) [ 88 ]. Yet, recent evidence suggests that a lower-intensity regimen of Fludrabine/Treosulfan (FT) possesses survival advantages over MAC or other reduced-intensity conditioning (RIC) regimens [ 89 ]. A comparison of the three types of conditioning regimens suggested indeed that FT was associated with a lower relapse risk than RIC (HR 0.55, 95% CI 0.42–0.73, p < 0.001), in a similar fashion to MAC (HR 0.61, 95% CI 0.28–0.77, p < 0.001) [ 89 ].…”

“…Yet, recent evidence suggests that a lower-intensity regimen of Fludrabine/Treosulfan (FT) possesses survival advantages over MAC or other reduced-intensity conditioning (RIC) regimens [ 89 ]. A comparison of the three types of conditioning regimens suggested indeed that FT was associated with a lower relapse risk than RIC (HR 0.55, 95% CI 0.42–0.73, p < 0.001), in a similar fashion to MAC (HR 0.61, 95% CI 0.28–0.77, p < 0.001) [ 89 ]. In contrast, patients receiving MAC had higher nonrelapse mortality (NRM) when compared to RIC (HR 1.44, 95% CI 1.15–1.8, p = 0.001) and FT, which had a similar NRM risk to RIC (HR 0.88, 95% CI 0.67–1.15, p = 0.35) [ 89 ].…”

“…A comparison of the three types of conditioning regimens suggested indeed that FT was associated with a lower relapse risk than RIC (HR 0.55, 95% CI 0.42–0.73, p < 0.001), in a similar fashion to MAC (HR 0.61, 95% CI 0.28–0.77, p < 0.001) [ 89 ]. In contrast, patients receiving MAC had higher nonrelapse mortality (NRM) when compared to RIC (HR 1.44, 95% CI 1.15–1.8, p = 0.001) and FT, which had a similar NRM risk to RIC (HR 0.88, 95% CI 0.67–1.15, p = 0.35) [ 89 ]. Thus, FT offers a comparable low relapse risk to MAC and a similar NRM risk to RIC, resulting in improved OS [ 89 ].…”

Allogeneic stem cell transplantation for patients with myelodysplastic syndromes

“…Due to its presumed more favorable organ toxicity profile, treosulfan has been incorporated in conditioning regimens for allo‐HSCT. A retrospective study from the EBMT registry for MDS patients showed that treosulfan in combination with fludarabine (Tre/Flu) was associated with lower risk of relapse (HR 0.55; p < .001) and higher OS (HR 0.72; p = .01) when compared with other MAC and other RIC regimens 45 . Recently, a phase III randomized study was published, which compared RIC Tre/Flu and Flu/Bu2 RIC regimen for AML/MDS patients, 50–70 years or younger patients with significant comorbidities (HCT‐CI >2).…”

Treosulphan versus busulphan: pros and cons

“…Shimoni et al . build on the existing literature to specifically describe outcomes in patients with MDS comparing FT with other RIC and MAC regimens 11 . In their analysis they confirm that FT has comparable non‐relapse mortality (NRM) to RIC regimens but at the same time less risk of relapse compared to both RIC and MAC regimens resulting in an improved OS.…”