Farahat N, Morilla A, Owusu-Ankomah K, Morilla R, Pinkerton C R, Treleaven J G, Matutes E, Powles R L, Catovsky D
Academic Department of Haematology and Cytogenetics, The Royal Marsden NHS Trust and Institute of Cancer Research, London.
Br J Haematol. 1998 Apr;101(1):158-64. doi: 10.1046/j.1365-2141.1998.00675.x.
The clinical significance of detecting minimal residual disease (MRD) in B-lineage acute lymphoblastic leukaemia (ALL) was evaluated by quantitative flow cytometry using a combination of TdT with CD10 and CD19. 53 patients with B-cell precursor ALL were followed during and after completion of treatment (median follow-up 23 months). Nine patients relapsed and MRD had been detected in six of them, 5-15 weeks before relapse despite morphological complete remission. 43 patients remain in clinical remission and in none of these was MRD detected. Disease-free survival based on the detection of MRD by flow cytometry showed a statistically significant difference between both groups (P<0.0001). The absence of MRD correlates with a low relapse rate, whereas the presence of MRD predicted early relapse. This study has shown that flow cytometry can improve the morphologic assessment of bone marrow (BM) remission status in B-lineage ALL. The finding of < 5% blasts in BM aspirates did not correlate with 'true' remission in a proportion of cases as residual leukaemic blasts were detected by flow cytometry in nine samples from six patients. On the other hand, the presence of > 5% blasts assessed by morphology was not necessarily a feature of relapse in five patients as these cells were shown to have a phenotype identical to normal TdT-negative B-cell precursors. Quantitative flow cytometry was more informative than conventional morphology to assess remission status and showed a strong correlation with clinical outcome. This methodology is useful to define MRD in the majority of patients with B-lineage ALL and should be tested in prospective clinical trials.
采用TdT与CD10和CD19联合检测的定量流式细胞术，评估B系急性淋巴细胞白血病（ALL）中检测微小残留病（MRD）的临床意义。53例B细胞前体ALL患者在治疗期间及治疗完成后接受随访（中位随访时间23个月）。9例患者复发，其中6例在复发前5 - 15周检测到MRD，尽管形态学上完全缓解。43例患者仍处于临床缓解期，这些患者均未检测到MRD。基于流式细胞术检测MRD的无病生存率在两组之间显示出统计学上的显著差异（P<0.0001）。MRD的缺失与低复发率相关，而MRD的存在预示着早期复发。本研究表明，流式细胞术可改善B系ALL中骨髓（BM）缓解状态的形态学评估。在一部分病例中，骨髓穿刺液中原始细胞<5%的发现与“真正”缓解不相关，因为通过流式细胞术在6例患者的9份样本中检测到残留的白血病原始细胞。另一方面，在5例患者中，形态学评估>5%原始细胞的存在不一定是复发的特征，因为这些细胞显示出与正常TdT阴性B细胞前体相同的表型。定量流式细胞术在评估缓解状态方面比传统形态学更具信息性，并且与临床结果显示出强烈的相关性。这种方法对于定义大多数B系ALL患者的MRD是有用的，并且应该在前瞻性临床试验中进行测试。
