高 CD45 表面表达决定了按照 ALL-BFM 2000 方案治疗的前体 B 细胞和 T 细胞急性淋巴细胞白血病患儿的复发风险。
High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol.
出版信息
Haematologica. 2014 Jan;99(1):103-10. doi: 10.3324/haematol.2013.090225. Epub 2013 Aug 2.
Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from intensified treatment. We earlier identified PTPRC (CD45) gene expression as a potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 was measured by flow cytometry in 1065 patients treated according to the ALL-BFM-2000 protocol. The 75(th) percentile was used as cut-off to distinguish a CD45-high from a CD45-low group. As mean CD45 expression was significantly higher in T-cell acute lymphoblastic leukemia than in B-cell-precursor acute lymphoblastic leukemia (P<0.0001), the analysis was performed separately in both groups. In B-cell-precursor acute lymphoblastic leukemia we observed a significant association of a high CD45 expression with older age, high initial white blood cell count, ETV6/RUNX1 negativity, absence of high hyperdiploidy (P<0.0001), MLL/AF4 positivity (P=0.002), BCR/ABL1 positivity (P=0.007), prednisone poor response (P=0.002) and minimal residual disease (P<0.0001). In T-cell acute lymphoblastic leukemia we observed a significant association with initial white blood cell count (P=0.0003), prednisone poor response (P=0.01), and minimal residual disease (P=0.02). Compared to CD45-low patients, CD45-high patients had a lower event-free survival rate (B-cell-precursor acute lymphoblastic leukemia: 72 ± 3% versus 86 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 60 ± 8% versus 78 ± 4%, P=0.02), which was mainly attributable to a higher cumulative relapse incidence (B-cell-precursor acute lymphoblastic leukemia: 22 ± 3% versus 11 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 31 ± 8% versus 11 ± 3%, P=0.003) and kept its significance in multivariate analysis considering sex, age, initial white blood cell count, and minimal residual disease in B-cell-precursor- and T-cell acute lymphoblastic leukemia, and additionally presence of ETV6/RUNX1, MLL/AF4 and BCR/ABL1 rearrangements in B-cell-precursor acute lymphoblastic leukemia (P=0.002 and P=0.025, respectively). Consideration of CD45 expression may serve as an additional stratification tool in BFM-based protocols. (ClinicalTrials.gov identifier: NCT00430118).
通过识别可能受益于强化治疗的其他高危患者，可以进一步提高儿童急性淋巴细胞白血病的治疗效果。我们之前已经确定了 PTPRC（CD45）基因表达作为一种潜在的新分层标志物，并对 CD45 蛋白表达的预后相关性进行了分析。在 1065 名按照 ALL-BFM-2000 方案治疗的患者中，采用流式细胞术测量 CD45。使用第 75 百分位数作为界值来区分 CD45 高组和 CD45 低组。由于 T 细胞急性淋巴细胞白血病的平均 CD45 表达明显高于 B 细胞前体急性淋巴细胞白血病（P<0.0001），因此分别在两组中进行了分析。在 B 细胞前体急性淋巴细胞白血病中，我们观察到高 CD45 表达与年龄较大、初始白细胞计数高、ETV6/RUNX1 阴性、不存在高超二倍体（P<0.0001）、MLL/AF4 阳性（P=0.002）、BCR/ABL1 阳性（P=0.007）、泼尼松反应不良（P=0.002）和微小残留疾病（P<0.0001）显著相关。在 T 细胞急性淋巴细胞白血病中，我们观察到与初始白细胞计数（P=0.0003）、泼尼松反应不良（P=0.01）和微小残留疾病（P=0.02）显著相关。与 CD45 低患者相比，CD45 高患者的无事件生存率较低（B 细胞前体急性淋巴细胞白血病：72±3%与 86±1%，P<0.0001；T 细胞急性淋巴细胞白血病：60±8%与 78±4%，P=0.02），这主要归因于累积复发率较高（B 细胞前体急性淋巴细胞白血病：22±3%与 11±1%，P<0.0001；T 细胞急性淋巴细胞白血病：31±8%与 11±3%，P=0.003），在 B 细胞前体和 T 细胞急性淋巴细胞白血病中考虑性别、年龄、初始白细胞计数和微小残留疾病以及 ETV6/RUNX1、MLL/AF4 和 BCR/ABL1 重排的存在时，该结果在多变量分析中仍具有统计学意义（P=0.002 和 P=0.025）。在基于 BFM 的方案中，考虑 CD45 表达可作为一种额外的分层工具。（临床试验标识符：NCT00430118）。
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