Long‐term outcome after a treosulfan‐based conditioning regimen for patients with acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

BACKGROUND Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post‐HCT relapse and regimen‐related toxicity remain significant barriers to long‐term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile. METHODS To investigate the role of treosulfan‐based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan‐based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease). The median patient age was 57 years (range, 20‐73 years). Donors were human leukocyte antigen‐identical siblings (n = 187), unrelated donors (n = 235), or mismatched related donors (n = 98). Conditioning regimens included treosulfan (42 g/m2 [n = 396], 36 g/m2 [n = 109], or 30 g/ m2 [n = 15]) with fludarabine or alkylating agents followed by infusion of hematopoietic stem cells (bone marrow, n = 52; peripheral blood, n = 468). RESULTS At a median follow‐up of 61 months, the 5‐year overall survival, leukemia‐free survival, relapse incidence, and nonrelapse mortality rates were 38%, 33%, 42%, and 25%, respectively. The incidence of grade II‐IV acute and chronic graft‐versus‐host disease was 24% (grade III‐V, 11%) and 38%, respectively. Only 11 patients (2%) developed veno‐occlusive disease, with two deaths (0.4%) from veno‐occlusive disease. CONCLUSIONS Treosulfan‐based conditioning regimens provide an acceptable long‐term survival with favorable nonrelapse mortality and a very low risk of veno‐occlusive disease. Further studies are needed to optimize the treosulfan‐based conditioning regimen for patients with AML. Cancer 2017;123:2671‐79. © 2017 American Cancer Society. A treosulfan‐based conditioning regimen provides acceptable long‐term survival with a low risk of early organ toxicity and acute graft‐versus‐host disease. The objective of future studies should be to compare treosulfan with the currently available ablative regimens and to define the best treosulfan combinations.