Borowitz M J, Shuster J, Carroll A J, Nash M, Look A T, Camitta B, Mahoney D, Lauer S J, Pullen D J
Pediatric Oncology Group, Chicago, IL 60611, USA.
Blood. 1997 Jun 1;89(11):3960-6.
This report describes the prognostic significance of the intensity of surface membrane antigen expression in a series of 1,231 children older than 1 year with newly diagnosed B-precursor acute lymphoblastic leukemia (ALL) treated on Pediatric Oncology Group (POG) treatment protocols. All patients had dual-color flow cytometric immunophenotyping performed at a central reference laboratory with a standard panel of monoclonal antibodies. The flow cytometers used in the study were calibrated with a standard fluorescence microparticle that permitted conversion of relative fluorescence channels to standard units of mean equivalents of soluble fluorochrome (MESF). In univariate analysis, fluorescence intensity of CD45 and CD20 was significantly associated with event-free survival (EFS), whereas other markers showed no significant correlation with outcome. Patients whose blasts were greater than the 75th percentile of intensity for CD45 (corresponding to 18,000 MESF units with CD45-FITC, or about 8% of the intensity of normal lymphocytes) fared significantly worse than those with lower-density CD45, and those whose blasts were greater than the 25th percentile of intensity for CD20 (corresponding to 17,900 MESF units with CD20-PE) had a poorer EFS. The intensity of both CD45 and CD20 was independently correlated with outcome. There was no significant correlation between intensity of expression of either antigen and traditional clinical risk factors, ploidy, or t(9;22) or t(1;19). All patients with t(4;11) had CD45 intensity greater than the 75th percentile, but CD45 intensity retained its prognostic significance after adjusting for t(4;11). In multivariate analysis, both CD45 intensity greater than the 75th percentile and CD20 intensity greater than the 25th percentile were significantly correlated with poor outcome independently of previously reported poor prognostic factors including National Cancer Institute (NCI) risk group, ploidy, trisomies of 4 and 10, and adverse translocations including t(1;19), t(9;22), and t(4;11). We conclude that in childhood B-precursor ALL, the intensity of expression of CD20 and CD45 provides prognostic information not available from simple consideration of antigen expression as positive or negative, and adds to that obtained from traditional clinical and biologic risk factors.
本报告描述了1231例1岁以上新诊断的B前体急性淋巴细胞白血病（ALL）患儿表面膜抗原表达强度的预后意义，这些患儿接受了儿科肿瘤学组（POG）治疗方案的治疗。所有患者均在中央参考实验室采用标准单克隆抗体组合进行双色流式细胞术免疫表型分析。研究中使用的流式细胞仪用标准荧光微粒进行校准，该微粒可将相对荧光通道转换为可溶性荧光染料平均当量（MESF）的标准单位。在单变量分析中，CD45和CD20的荧光强度与无事件生存期（EFS）显著相关，而其他标志物与预后无显著相关性。原始细胞CD45强度高于第75百分位数（对应于CD45-FITC的18000 MESF单位，或约为正常淋巴细胞强度的8%）的患者预后明显差于CD45密度较低的患者，原始细胞CD20强度高于第25百分位数（对应于CD20-PE的17900 MESF单位）的患者EFS较差。CD45和CD20的强度均与预后独立相关。两种抗原的表达强度与传统临床危险因素、倍性或t(9;22)或t(1;19)之间均无显著相关性。所有t(4;11)患者的CD45强度均高于第75百分位数，但在调整t(4;11)后，CD45强度仍保留其预后意义。在多变量分析中，CD45强度高于第75百分位数和CD20强度高于第25百分位数均与不良预后显著相关，独立于先前报道的不良预后因素，包括美国国立癌症研究所（NCI）风险组、倍性、4号和10号染色体三体以及不良易位，包括t(1;19)、t(9;22)和t(4;11)。我们得出结论，在儿童B前体ALL中，CD20和CD45的表达强度提供了仅简单考虑抗原表达为阳性或阴性所无法获得的预后信息，并补充了从传统临床和生物学危险因素中获得的信息。
