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

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/m2 (day −1) (BuMel). In a subsequent (TreoMel) cohort, 20 patients received treosulfan 14 g/m2 (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.

Combining BeEAM with Brentuximab Vedotin for High-Dose Therapy in CD30 Positive Lymphomas before Autologous Transplantation—A Phase I Study

“…2 (1-4) Patients with at least 1 identified pathogen, n (%) 7 (58%) Patients with >1 identified pathogen, n (%) 1 (8%) Bacteria, Gram-positive 10,11 , n (%) 5 (42%) Bacteria, Gram-negative 10,12 , n (%) 3 (25%) Viral, n (%) 0 (0%) Fungal, n (%) 0 (0%)…”

“…One option as a conditioning regimen before ASCT for these entities is the BeEAM regimen (bendamustine, etoposide, cytarabine, and melphalan) as it offers comparable efficacy to the BEAM (BCNU, etoposide, cytarabine, and melphalan) regimen, avoids BCNU-related pulmonary toxicities, and its commercial availability is decisively more reliable [3][4][5][6][7][8]. However, various other drug combinations have been or are being evaluated [9,10].…”

“…First-line therapies ABVD 5 , n (%) 3 (25%) 0 (0%) 3 (43%) 3 BEACOPP 6 , n (%) 2 (17%) 0 (0%) (29%) CHOP 7 , n (%) 3 (25%) 3 (60%) 0 (0%) Others, n (%) 4 (33%) 2 9 (40%) 2 10 (29%)…”

Low expression of H3K27me3 is associated with poor prognosis in conventional chordoma

“…Currently, there are two reasons for the reduction of H3K27me3. One reason is that H3K27M mutation blocks the methylation of K27 in the histone tail and reduces the overall level of H3K27me3 in cells ( 33 ), another reason is that in MPNSTs, when polycomb complex 2 (PRC2) is mutated, even without K27M mutation, histone H3 methylation is still affected, and H3K27me3 expression is lost ( 34 ). However, all of our cases showed positive immunohistochemistry for H3K27M, confirming that the mutation of H3K27M does not occur in chordoma.…”

Efficacy and Safety of High-Dose Chemotherapy with Treosulfan and Melphalan in Multiple Myeloma

“…In a retrospective study, treosulfan single-drug conditioning before first-line allogenic stem cell transplantation showed improved OS when compared to myeloablative conditioning regimens [19]. In previous work, our group assessed the efficacy and safety of TreoMel in a cohort of acute myeloid leukemia (AML) patients undergoing ASCT, showing comparable efficacy and safety results to HDCT with BuMel [20]. Moreover, no cases of irreversible alopecia and less incidence of neurologic toxicity were observed with the TreoMel regimen [20].…”