Comparison of Melphalan Combined with Treosulfan or Busulfan as High-Dose Chemotherapy before Autologous Stem Cell Transplantation in AML

SIMPLE SUMMARY: Different consolidation strategies are available for acute myeloid leukemia (AML) patients fit for intensive treatment. For favorable- or intermediate-risk AML, high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is one of these options. Busulfan plus melphalan is a frequently used and efficient HDCT regimen, but it bears neurotoxic potential and may cause irreversible alopecia, amongst other toxicities. Thus, improving HDCT regimens with lesser toxicity, albeit at comparable anti-leukemic efficacy, is wishful. We combined treosulfan with its more favorable toxicity profile with melphalan for HDCT and compared these patients with a group receiving busulfan/treosulfan. Whereas disease-free and overall survival did not differ significantly, the treosulfan regimen compared favorably, with the absence of neurotoxicity and irreversibly alopecia. Treosulfan serum levels by mass cytometry demonstrated considerable interindividual biovariability. Further studies should explore treosulfan/melphalan for HDCT/ASCT in AML, aiming to improve the quality of life of AML survivors and offer safer consolidation strategies. ABSTRACT: (1) Background: High-dose chemotherapy (HDCT) before autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML) patients predominantly combines busulfan with cyclophosphamide or melphalan. Treosulfan compares favorably regarding lower inter-individual bioavailability and neurotoxicity, but so far, had not been studied before ASCT in AML. (2) Methods: This single-center study investigated AML patients undergoing ASCT in CR1 between November 2017 and September 2020. The first 16 patients received busulfan 16 mg/kg b.w. (days −5 to −2) and melphalan 140 mg/m(2) (day −1) (BuMel). In a subsequent (TreoMel) cohort, 20 patients received treosulfan 14 g/m(2) (days −4 to −2) and melphalan. Plasma concentrations of busulfan and treosulfan were determined by mass spectrometry. (3) Results: Neutrophil engraftment and platelet recovery were similar, and PFS and OS were comparable. In only the BuMel cohort, patients reported central nervous toxicities, including seizures (6%) and encephalopathy (12%). The mean AUC for busulfan was 1471.32 μM*min, and for treosulfan it was 836.79 mg/L*h, with ranges of 804.1–2082 μM*min and 454.2–1402 mg/L*h. The peak values for busulfan ranged between 880.19–1734 μg/L and for treosulfan between 194.3–489.25 mg/L. (4) Conclusions: TreoMel appears to be safe and effective for pre-ASCT treatment in AML patients. Due to considerable interindividual biovariability, pharmacologic monitoring may also be warranted for the use of treosulfan.