追踪白血病干细胞及其对成人急性髓细胞白血病临床过程的影响。

Tracing Leukemia Stem Cells and Their Influence on Clinical Course of Adult Acute Myeloid Leukemia.

机构信息

Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

Clin Lymphoma Myeloma Leuk. 2020 Jun;20(6):383-393. doi: 10.1016/j.clml.2019.11.018. Epub 2020 Feb 12.

DOI:10.1016/j.clml.2019.11.018

PMID:32201129

Abstract

BACKGROUND

Acute myeloid leukemia (AML) evolves from neoplastic transformation of stem cell disease termed "leukemia stem cells" (LSCs). An unsatisfactory response to AML therapy is determined by the presence of minimal residual disease (MRD). The predominance of LSCs might anticipate sustained MRD results. The present study aimed to demonstrate the effect of LSCs on MRD at induction days 14 and 28 on overall survival (OS) and disease-free survival (DFS) and to compare LSC expression with MRD status.

PATIENTS AND METHODS

A total of 84 patients with de novo adult AML underwent testing using LSC panels for CD38/CD123/CD34/CD45 and CD90/CD133/CD45/CD33 and different regular MRD panels.

RESULTS

At day 14 after induction, the high expression of CD123 and CD133 had adverse effects on both OS and DFS (P = .004 and P ≤ .001 and P ≤ .001 and P ≤ .001, respectively). Greater expression of CD34/CD38/CD123 resulted in unfavorable OS and DFS (P ≤ .001 for both). Both CD34/CD38/CD123 and CD34/CD38/CD123 expression at day 14 after induction had an adverse effect on DFS only (P < .001 and P = .029, respectively). On multivariate analysis, CD133 expression and MRD status were independent prognostic parameters (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2-4.4; P = .015; and HR, 2.9; 95% CI, 1.0-7.9; P = .041). At day 28 after induction, MRD and increased CD123/CD34, CD34/CD38/CD123, CD133/CD33 expression were associated with inferior OS (P = .016, P = .0035, P = .0.002, and P = .002, respectively). MRD and high expression of CD34CD123, CD133/CD33, CD34/CD38/CD123 were associated with inferior DFS (P < .001, P = .002, P < .001, P < .001, respectively). On multivariate analysis, only CD133/CD33 expression was the independent prognostic factor (HR, 3.1; 95% CI, 1.5-6.7; P = .003).

CONCLUSIONS

Estimation of LSC expression is a sensitive indicator of the response to therapy in adult patients with AML and might be a better prognosticator than the findings from regular MRD panels.

摘要

背景

急性髓系白血病（AML）是由被称为“白血病干细胞”（LSCs）的干细胞疾病的肿瘤转化而来。对 AML 治疗的反应不理想取决于微小残留病（MRD）的存在。LSCs 的优势可能预示着持续的 MRD 结果。本研究旨在表明诱导第 14 天和第 28 天 LSCs 对总生存期（OS）和无病生存期（DFS）的 MRD 的影响，并比较 LSC 表达与 MRD 状态。

患者和方法

84 例新诊断的成人 AML 患者接受了用于检测 CD38/CD123/CD34/CD45 和 CD90/CD133/CD45/CD33 的 LSC 面板以及不同的常规 MRD 面板的检测。

结果

诱导后第 14 天，CD123 和 CD133 的高表达对 OS 和 DFS 均有不良影响（P =.004 和 P ≤.001 和 P ≤.001 和 P ≤.001，分别）。CD34/CD38/CD123 表达增加导致 OS 和 DFS 不良（均 P ≤.001）。诱导后第 14 天的 CD34/CD38/CD123 和 CD34/CD38/CD123 表达均对 DFS 有不良影响（均 P <.001 和 P =.029）。多变量分析显示，CD133 表达和 MRD 状态是独立的预后参数（风险比[HR]，2.3；95%置信区间[CI]，1.2-4.4；P =.015；和 HR，2.9；95%CI，1.0-7.9；P =.041）。诱导后第 28 天，MRD 和增加的 CD123/CD34、CD34/CD38/CD123、CD133/CD33 表达与 OS 不良相关（P =.016、P =.0035、P =.002 和 P =.002）。MRD 和 CD34CD123、CD133/CD33、CD34/CD38/CD123 高表达与 DFS 不良相关（均 P <.001）。多变量分析显示，只有 CD133/CD33 表达是独立的预后因素（HR，3.1；95%CI，1.5-6.7；P =.003）。