Wang Ya-Zhe, Hao Le, Chang Yan, Jiang Qian, Jiang Hao, Zhang Le-Ping, He Ling-Ling, Yuan Xiao-Ying, Qin Ya-Zhen, Huang Xiao-Jun, Liu Yan-Rong
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Leuk Res. 2018 Sep;72:12-19. doi: 10.1016/j.leukres.2018.07.012. Epub 2018 Jul 27.
A seven-color panel was used to detect minimal residual disease (MRD) in T cell acute lymphoblastic leukemia (T-ALL) via flow cytometry (FCM). Its availability and clinical significance were studied in T-ALL patients with newly diagnosed (n = 64), relapsed (n = 48) and morphologically complete remission (n = 103). The following four features were used to identify immature cCD3+ T cells: CD34+, TdT+, but mCD3-/dim+, and CD45dim+. Among these features, either TdT or CD34 expression was the most useful and were found in 93.8% of patients at diagnosis and 86.7% of patients who relapsed. Although some of the immature markers had disappeared in 23 of 59 cases after therapy, only one case presented with a false negative MRD. Of the 74 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), MRD-positive patients showed a higher relapse rate, a higher cumulative incidence of relapse at 4 years and a shorter median relapse-free survival than MRD-negative patients at post-HSCT(72.7% vs 17.3%, P = 0.000; 100% vs 19.9%, P < 0.0001; and 16 months vs undefined, P < 0.0001). We demonstrated that this panel could be applied to>97% of T-ALL patients to detect MRD and predict relapse after allo-HSCT even in the absence of the initial immunophenotype.
采用七色流式细胞术检测T细胞急性淋巴细胞白血病(T-ALL)微小残留病(MRD)。研究了其在新诊断(n = 64)、复发(n = 48)和形态学完全缓解(n = 103)的T-ALL患者中的可用性及临床意义。采用以下四个特征来识别未成熟的胞浆CD3+ T细胞:CD34+、末端脱氧核苷酸转移酶(TdT)+,但膜表面CD3- /弱阳性,以及CD45弱阳性。在这些特征中,TdT或CD34表达最具诊断价值,在诊断时93.8%的患者以及复发患者中的86.7%可检测到。虽然治疗后59例中有23例部分未成熟标志物消失,但仅1例出现MRD假阴性。在74例接受异基因造血干细胞移植(allo-HSCT)的连续患者中,MRD阳性患者在HSCT后复发率更高、4年累积复发率更高且无复发生存期中位数更短,与MRD阴性患者相比(72.7%对17.3%,P = 0.000;100%对19.9%,P < 0.0001;16个月对未明确,P < 0.0001)。我们证明该检测方法可应用于>97%的T-ALL患者以检测MRD并预测allo-HSCT后的复发,即使在缺乏初始免疫表型的情况下也适用。