Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
University of Barcelona, Barcelona, Spain.
Eur J Haematol. 2013 Sep;91(3):209-218. doi: 10.1111/ejh.12130. Epub 2013 Jul 25.
Most patients with acute myeloid leukemia (AML) and genetic rearrangements involving the core binding factor (CBF) have favorable prognosis. In contrast, a minority of them still have a high risk of leukemia recurrence. This study investigated the adverse features of CBF AML that could justify investigational therapeutic approaches.
One hundred and fifty patients (median age 42 yr, range 16-69) with CBF AML (RUNX1-RUNX1T1 n = 74; CBFB-MYH11 n = 76) were prospectively enrolled into two consecutive CETLAM protocols at 19 Spanish institutions. Main clinic and biologic parameters were analyzed in the whole series. In non-selected cases with available DNA samples, the impact of molecular characterization and minimal residual disease (MRD) was also studied.
Overall, complete remission (CR) rate was 89% (94% in ≤50 yr old and 72% in >50 yr, P = 0.002). At 5 yr, cumulative incidence of relapse (CIR) was 26 ± 1%, disease-free survival (DFS) 62 ± 6%, and overall survival (OS) 66 ± 4%. In multivariate analyses, leukocyte count above 20 × 10(9) /L, BAALC over-expression, and high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy (CT) led to increased relapse rate. Regarding OS, age >50 yr, leukocyte count above 20 × 10(9) /L, and increased MN1 expression were adverse features.
Age, leukocyte counts, BAALC, and MN1 gene expressions as well as high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy are useful tools to predict the outcome and should be considered for risk-adapted therapy.
大多数伴有涉及核心结合因子（CBF）的基因重排的急性髓系白血病（AML）患者具有良好的预后。相比之下，少数患者仍存在白血病复发的高风险。本研究旨在探讨可作为探索性治疗方法依据的 CBF-AML 的不良特征。
19 家西班牙机构连续前瞻性纳入 150 例 CBF-AML 患者（中位年龄 42 岁，范围 16-69 岁），包括 74 例 RUNX1-RUNX1T1 和 76 例 CBFB-MYH11。对全系列患者的主要临床和生物学参数进行分析。在未选择的有可用 DNA 样本的病例中，还研究了分子特征和微小残留病（MRD）的影响。
总体而言，完全缓解（CR）率为 89%（≤50 岁为 94%，>50 岁为 72%，P=0.002）。5 年时，累积复发率（CIR）为 26%±1%，无病生存率（DFS）为 62%±6%，总生存率（OS）为 66%±4%。多变量分析显示，诱导化疗后白细胞计数>20×10(9)/L、BAALC 过表达以及 RUNX1-RUNXT1 或 CBFB-MYH11 高拷贝数与复发率增加相关。对于 OS，年龄>50 岁、白细胞计数>20×10(9)/L 和 MN1 表达增加是不良特征。
年龄、白细胞计数、BAALC、MN1 基因表达以及诱导化疗后 RUNX1-RUNXT1 或 CBFB-MYH11 的高拷贝数是预测预后的有用工具，应考虑用于风险适应性治疗。
