Nagler Arnon, Labopin Myriam, Beelen Dietrich, Ciceri Fabio, Volin Liisa, Shimoni Avichai, Foá Roberto, Milpied Noel, Peccatori Jacopo, Polge Emmanuelle, Mailhol Audrey, Mohty Mohamad, Savani Bipin N
Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation Paris Study Office/European Center for Biostatistical and Epidemiological Evaluation in Hematopoietic Cell Therapy (CEREST-TC), Paris, France.
Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Cancer. 2017 Jul 15;123(14):2671-2679. doi: 10.1002/cncr.30646. Epub 2017 Mar 22.
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.
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/m [n = 396], 36 g/m [n = 109], or 30 g/ m [n = 15]) with fludarabine or alkylating agents followed by infusion of hematopoietic stem cells (bone marrow, n = 52; peripheral blood, n = 468).
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.
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.
异基因造血细胞移植（HCT）是急性髓系白血病（AML）患者的一种治愈性疗法。然而，HCT后复发和与治疗方案相关的毒性仍然是长期生存的重大障碍。近年来，人们探索了新的预处理方案以改善AML患者的移植结局。曲奥舒凡兼具强效免疫抑制和抗白血病作用，且毒性较低。
为研究基于曲奥舒凡的预处理的作用，欧洲血液和骨髓移植学会急性白血病工作组对2000年至2012年间接受基于曲奥舒凡的预处理并进行HCT的520例成年AML患者进行了一项注册分析，其中包括225例首次完全缓解的患者、107例第二次或更晚完全缓解的患者以及188例有活动期/晚期疾病的患者（188例中有88例为原发性难治性疾病）。患者中位年龄为57岁（范围20 - 73岁）。供者为人类白细胞抗原相合的同胞（n = 187）、无关供者（n = 235）或不相合的相关供者（n = 98）。预处理方案包括曲奥舒凡（42 g/m²[n = 396]、36 g/m²[n = 109]或30 g/m²[n = 15]）联合氟达拉滨或烷化剂，随后输注造血干细胞（骨髓，n = 52；外周血，n = 468）。
中位随访61个月时，5年总生存率、无白血病生存率、复发率和非复发死亡率分别为38%、33%、42%和25%。II - IV级急性和慢性移植物抗宿主病的发生率分别为24%（III - V级为11%）和38%。仅11例患者（2%）发生了静脉闭塞性疾病，其中2例死于静脉闭塞性疾病（0.4%）。
基于曲奥舒凡的预处理方案可提供可接受的长期生存，非复发死亡率良好，静脉闭塞性疾病风险极低。需要进一步研究以优化AML患者基于曲奥舒凡的预处理方案。《癌症》2017年；123:2671 - 79。©2017美国癌症协会
