Yoon Jae-Ho, Kim Hee-Je, Park Sung-Soo, Jeon Young-Woo, Lee Sung-Eun, Cho Byung-Sik, Eom Ki-Seong, Kim Yoo-Jin, Lee Seok, Min Chang-Ki, Cho Seok-Goo, Kim Dong-Wook, Lee Jong-Wook, Min Woo-Sung
Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Biol Blood Marrow Transplant. 2017 Apr;23(4):588-597. doi: 10.1016/j.bbmt.2017.01.070. Epub 2017 Jan 12.
The role of autologous hematopoietic cell transplantation (auto-HCT) for postremission therapy of acute myeloid leukemia is yet to be elucidated. We retrospectively analyzed 240 patients treated with auto-HCT in first remission. All patients were treated with standard induction chemotherapy, and CD34 stem cells were collected at each cycle of consolidation. Stem cells were infused after total body irradiation (1200 cGy), cytarabine (9 g/m), and melphalan (100 mg/m). Estimated 5-year overall survival, disease-free survival (DFS), cumulative incidence of relapse (CIR), and nonrelapse mortality were 58.4%, 55.3%, 38.8%, and 5.9%, respectively. We identified that poor-risk karyotype showed very poor outcome after auto-HCT, and then analyzed 85 patients with good to intermediate-risk molecular cytogenetics with available molecular study results and markers for minimal residual disease (MRD) such as WT1 and core-binding factor (CBF) associated MRD (ie, AML1/ETO and CBFβ/MYH11). Our data identified that old age, pre-HCT markers for MRD, and high post-HCT WT1, high dose of CD34 stem cell (≥4.5 × 10/kg) infusion, and c-kit or FLT3-ITD mutations were associated with higher relapse rate and poor DFS. Using pre-HCT parameters, except for post-HCT WT1, multivariate analysis revealed that patients with young age (<40 years old), no adverse mutations, and limited dose of CD34 stem cells might be good candidate for auto-HCT (3-year DFS and CIR were 83.4% and 16.6%, respectively). Young patients with good- to intermediate-risk molecular cytogenetics may benefit from auto-HCT if stem cell dose is limited.
自体造血细胞移植（auto-HCT）在急性髓系白血病缓解后治疗中的作用尚未阐明。我们回顾性分析了240例首次缓解期接受auto-HCT治疗的患者。所有患者均接受标准诱导化疗，并在巩固治疗的每个周期采集CD34⁺干细胞。干细胞在全身照射（1200 cGy）、阿糖胞苷（9 g/m²）和马法兰（100 mg/m²）后输注。估计5年总生存率、无病生存率（DFS）、复发累积发生率（CIR）和非复发死亡率分别为58.4%、55.3%、38.8%和5.9%。我们发现高危核型在auto-HCT后预后很差，然后分析了85例具有良好至中危分子细胞遗传学且有可用分子研究结果以及微小残留病（MRD）标志物（如WT1和核心结合因子（CBF）相关MRD，即AML1/ETO和CBFβ/MYH11）的患者。我们的数据表明，老年、HCT前MRD标志物、HCT后高WT1、高剂量CD34⁺干细胞（≥4.5×10⁶/kg）输注以及c-kit或FLT3-ITD突变与较高的复发率和不良DFS相关。使用HCT前参数，除了HCT后WT1外，多变量分析显示年龄较轻（<40岁）、无不良突变且CD34⁺干细胞剂量有限的患者可能是auto-HCT的良好候选者（3年DFS和CIR分别为83.4%和16.6%）。具有良好至中危分子细胞遗传学的年轻患者如果干细胞剂量有限，可能会从auto-HCT中获益。
