Augmented myeloablative conditioning with thiotepa in acute myeloid leukemia–improved outcomes with similar toxicity

Myeloablative doses of busulfan (Bu) with fludarabine (Flu) have reduced toxicity, however, limited by an increased relapse rate. We aimed to improve outcome of Flu-Bu regimen by augmentation with thiotepa (TT) (10 mg/kg). Eighty-nine patients with AML, 44 patients conditioned with Flu-Bu (group 1), and 45 patients augmented with TT (Flu-Bu-TT, group 2), were retrospectively analyzed. Primary objectives were toxicity and outcomes. Major toxicities were comparable: mucositis (p = 1.0), sepsis (p =.7), severe venocclusive disease of liver (VOD) (p = 1.0), and non-relapse mortality (NRM) (22 vs. 22%, p =.7). Five-year disease-free survival was significantly better in group 2 compared to group 1 (62 vs. 38%, p =.02). Five-year overall survival (OS) showed trend toward benefit in group 2 (62 vs. 42%, p =.06). Lower relapse rate in group 2 (14 vs. 46%, p =.005) contributed to better outcomes. Augmented regimen has better disease-free survival (DFS) (mainly due to reduced relapse rate) and similar toxicities as compared to Flu-Bu.Key points  Assessing the addition of TT to myeloablative conditioning (Flu, Bu) in patients undergoing allogeneic stem cell transplant for acute myeloid leukemia with regard to relapse rate, disease-free survival and toxicity.  Addition of thiotepa improves disease-free survival and shows trend toward benefit in overall survival, by reducing relapses without additional toxicity.