Treosulfan in conjunction with fludarabine may yield superior outcomes compared with busulfan for conditioning prior to allogeneic haemopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), according to research published in The Lancet Haematology.

More than half of HSCTs conducted for patients with any malignancy worldwide are for those with AML or MDS. Although this procedure can lead to long-term health improvements, many patients experience disease recurrence, and age, performance status, and pretransplant comorbidity or organ function impairment each correlate with risk for nonrelapse mortality.

Given the risk for nonrelapse mortality, there is ongoing controversy about whether to recommend maximum tolerable or minimum effective conditioning regimens prior to HSCT. Although busulfan forms the basis of a widely used regimen, some data suggest that treosulfan — a water-soluble, bifunctional alkylating drug — may be a noninferior option.

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For this randomized phase 3 trial, researchers assigned 460 patients to receive busulfan plus fludarabine (240 patients) or treosulfan plus fludarabine (220 patients). In the busulfan group, 138 patients had AML, 102 had MDS, 149 were male, 229 were 50 years or older, and 140 had a HSCT-comorbidity index (HCT-CI) score of greater than 2. In the treosulfan group, 155 patients had AML, 65 had MDS, 130 were male, 205 were 50 years or older, and 131 had an HCT-CI score of greater than 2.

Median follow-up was 17.4 months in the busulfan group and 15.4 months in the treosulfan group. An event occurred in 42% of patients who received busulfan and 31% of patients in the treosulfan group. Event-free survival at 24 months was 50.4% with busulfan compared with 64% with treosulfan (hazard ratio, 0.65; P <.0001 for noninferiority; P =.0051 for superiority); overall survival at 24 months was 56.4% with busulfan compared with 71.3% with treosulfan (hazard ratio, 0.61; P =.0082).

However, the rates of disease relapse or progression were similar between patients receiving busulfan and treosulfan (21% vs 20%). The rates of adverse events were also similar between the groups, with 54% and 53% of patients in the busulfan and treosulfan groups, respectively, experienced grade 3 or worse events.

The authors concluded that the treosulfan regimen exhibited improved event-free and overall survival, HSCT-related mortality, and nonrelapse mortality compared with the busulfan regimen, suggesting that “this regimen has the potential to become a standard preparative regimen before allogeneic HSCT in patients with AML and MDS at increased mortality risk for myeloablative conditioning.”


  1. Beelen DW, Trenschel R, Stelljes M, et al. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial [published online October 9, 2019]. Lancet Haematol. doi:10.1016/S2352-3026(19)30157-

This article originally appeared on Hematology Advisor