Deeg HJ, et al. - Researchers designed this prospective randomized phase II “pick the winner” trial to assess the efficacy of transplant conditioning with treosulfan/fludarabine ± 2 Gy total body irradiation (TBI) in reducing post-transplant relapse in patients with myelodysplastic syndrome/chronic myelomonocytic leukemia (MDS/CMML) or acute myeloid leukemia (AML). Here, in high-risk patients up to 70 years of age, treosulfan/fludarabine/low-dose TBI provided effective conditioning for allogeneic HCT. Patients with AML demonstrated more profound effect with the addition of TBI than those with MDS. A lower overall success rate was observed in association with high-risk disease features.

• Researchers assessed the efficacy in 100 patients [2–70 (median 57) years of age], with myelodysplastic syndrome/chronic myelomonocytic leukemia (MDS/CMML; n=51) or acute myeloid leukemia (AML; n=49).
• Patients were administered intravenous (IV) treosulfan, 14 g/m²/day on days -6 to -4 and IV fludarabine, 30 mg/m²/day on days -6 to -2, alone or combined with 2 Gy TBI (day 0).
• Related (n= 43) or unrelated (n=57) donors were observed.  
• All subsequent patients received TBI, when a planned interim analysis demonstrated superior PFS in the TBI arm (p=0.04).
• The 1-year overall survival (OS) was 80% for the TBI arm and 69% for the non-TBI arm with a follow-up of 12–40 (median 20) months.
• Findings revealed the 1-year cumulative relapse incidence of 22% and 34%, respectively (p=0.06).
• The 1-year relapse incidence was 15% and 31% (p=0.20) among patients with low risk disease, and 26% and 36% (p=0.18), respectively for patients with high-risk disease .
• The 1-year relapse incidence was 27% vs 33% (p=0.49) among MDS patients, and 16% vs 35% (p=0.05) among AML patients.
• Patients with unfavorable cytogenetics indicated the largest difference, with 1-year relapse incidences of 31% and 63% (p=0.18), respectively.
• In this high risk patient population, non-relapse mortality was 9% at 6 months and did not differ between arms.