Bradstock K, Matthews J, Benson E, Page F, Bishop J
Department of Haematology, Westmead Hospital, New South Wales, Australia.
Blood. 1994 Aug 15;84(4):1220-5.
The diagnostic and prognostic value of immunophenotyping with 18 murine monoclonal antibodies (MoAbs) to a variety of leukocyte differentiation antigens was assessed in 168 adults aged 15 to 60 years with acute myeloid leukemia (AML). Patients were entered on the multicentre Australian Leukaemia Study Group M4 protocol, and were randomized to receive either standard or high-dose Ara-C together with daunorubicin and etoposide as induction chemotherapy, followed by standard consolidation and maintenance therapy. Diagnostic bone marrow aspirate (152 cases) or peripheral blood samples (16) were analyzed by indirect immunofluorescence and flow cytometry. MoAbs used were directed at myeloid (CD11b, CD13, CD14, CD15, CD33, CD41), lymphoid (CD2, CD3, CD7, CD9, CD10, CD19), or stem cell (HLA-DR, CD34, c-kit receptor) antigens, as well as the leukocyte integrins CD18 and CD49e, and the transferrin receptor CD71. Of the myeloid markers, CD13 and CD33 were the most useful diagnostically (71% and 79% of cases positive, respectively), with CD11b, CD14, and CD15 less commonly positive. A minority of cases expressed lymphoid antigens, either T cell (CD2 16%, CD3 7%, CD7 28%) or B cell (CD10 2%, CD19 7%). CD34 was detected on 42% and c-kit receptor on 48%. When patients were analyzed for response to treatment, CD2, CD9, and CD14 were significantly associated with complete remission rate: cases expressing these antigens had a poorer response than negative cases. In univariate analysis, CD11b+ cases had shorter periods of remission (relative risk of relapse, 2.33; P = .003) and shorter survival (relative death rate, 1.91; P = .006). In multivariate analysis, adjusting for other prognostic factors, CD9 and CD11b were significantly predictive of shorter survival. No other marker had a significant predictive effect. We conclude that myeloid MoAbs are useful in confirming the diagnosis of AML, but their prognostic value may be limited to CD11b. Lymphoid antigen expression is a consistent phenomenon in a minority of cases of AML, but appears to have little clinical significance.
对168例年龄在15至60岁之间的急性髓系白血病（AML）成年患者，评估了用18种针对多种白细胞分化抗原的鼠单克隆抗体（MoAbs）进行免疫表型分析的诊断和预后价值。患者按照澳大利亚白血病研究组多中心M4方案入组，并随机接受标准剂量或高剂量阿糖胞苷联合柔红霉素和依托泊苷作为诱导化疗，随后进行标准巩固和维持治疗。通过间接免疫荧光和流式细胞术分析诊断性骨髓穿刺液（152例）或外周血样本（16例）。所用的MoAbs针对髓系（CD11b、CD13、CD14、CD15、CD33、CD41）、淋巴系（CD2、CD3、CD7、CD9、CD10、CD19）或干细胞（HLA-DR、CD34、c-kit受体）抗原，以及白细胞整合素CD18和CD49e，和转铁蛋白受体CD71。在髓系标志物中，CD13和CD33在诊断上最有用（分别有71%和79%的病例呈阳性），而CD11b、CD14和CD15呈阳性的情况较少见。少数病例表达淋巴系抗原，要么是T细胞（CD2 16%、CD3 7%、CD7 28%）要么是B细胞（CD10 2%、CD19 7%）。42%的病例检测到CD34，48%的病例检测到c-kit受体。当分析患者的治疗反应时，CD2、CD9和CD14与完全缓解率显著相关：表达这些抗原的病例比阴性病例反应更差。在单变量分析中，CD11b阳性的病例缓解期较短（复发相对风险为2.33；P = 0.003）且生存期较短（相对死亡率为1.91；P = 0.006）。在多变量分析中，校正其他预后因素后，CD9和CD11b显著预测生存期较短。没有其他标志物有显著的预测作用。我们得出结论，髓系MoAbs有助于确诊AML，但其预后价值可能仅限于CD11b。淋巴系抗原表达在少数AML病例中是一种持续现象，但似乎临床意义不大。
