多参数流式细胞术与实时定量PCR技术检测Ph阳性急性B淋巴细胞白血病异基因造血干细胞移植前微小残留病的预后意义比较

OBJECTIVE: To explore the different values of minimal residual disease（MRD）detection by multiparameter flow cytometry（MFC）and real-time quantitative polymerase chain reaction（RQ-PCR）before hematopoietic stem cell transplantation（HSCT）for predicting relapse, leukemia-free survival（LFS）, and overall survival（OS）in Philadelphia chromosome-positive ALL（Ph(+) ALL）. METHODS: A retrospective study（n＝280）was performed. MRD was determined using multiparameter flow cytometry and RQ-PCR. RESULTS: MRD analysis with MFC and RQ-PCR of the BCR-ABL fusion transcript showed a strong correlation before transplantation. The positive rates of MRD detected by MFC and RQ-PCR before transplantation were 25.7％（72/280）and 60.7％（170/280）, respectively. MFC MRDpositive（MRDpos）Ph(+) ALL patients had a higher 3 year cumulative incidences of relapse（CIR）than did MFC MRD-negative（MRDneg）Ph(+) ALL patients（23.6％ vs 8.6％; P<0.001）. However, the RQ-PCR MRDpos group had similar rates of 3 year OS, LFS, and NRM compared with those in the RQ-PCR MRDneg group. Moreover, patients with RQ-PCR MRD ≥1％ experienced higher 3 year CIR（23.1％ vs 11.4％ ; P＝0.032）, lower LFS（53.8％ vs 74.4％ ; P＝0.015）, and OS（57.7％ vs 79.1％ ; P＝0.009）compared with the RQ-PCR MRD<1％ group. Multivariate analyses confirmed the association of MFC MRD status and RQ-PCR MRD ≥1％ with outcomes（P<0.05）. The sensitivity, specificity, positive predictive value（PPV）, and negative predictive value（NPV）of MFC detection MRD to predict recurrence were 48.50％, 77.56％, 23.62％, and 87.16％, respectively. Moreover, the sensitivity, specificity, PPV, and NPV were 23.00％, 88.59％, 17.15％, and 91.84％, respectively, when RQ-PCR MRD ≥1％ was used to predict recurrence. Additionally, the sensitivity, specificity, PPV, and NPV were 54.29％, 73.88％, 45.7％ and 91.87％, respectively, when MRD-positive status before transplantation（MFC MRDpos or RQ-PCR MRD ≥1％）was used to predict recurrence after transplantation. CONCLUSION: Both MFC and RQ-PCR detection of pretransplant MRD levels can predict the prognosis of Ph(+) B-ALL patients receiving allogeneic HSCT. MFC MRD-positive status before transplantation is the risk factor of leukemia recurrence after transplantation. The combined use of the two methods（MFC MRDpos or RQ-PCR MRD ≥1％）can improve the sensitivity, PPV, and NPV of predicting recurrence and help to better screen high-risk patients for intervention, thereby improving clinical efficacy.