[Comparison of prognostic significance between multiparameter flow cytometry and real-time quantitative polymerase chain reaction in the detection of minimal residual disease of Philadelphia chromosome-positive acute B lymphocytic leukemia before allogeneic hematopoietic stem cell transplantation].

Affiliation

Wang XY(1), Chang YJ(1), Liu YR(1), Qin YQ(1), Xu LP(1), Wang Y(1), Zhang XH(1), Yan CH(1), Sun YQ(1), Huang XJ(1), Zhao XS(1).
Author information:
(1)Peking University People's Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.

Abstract

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 MRD-positive (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. Conclusions: 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.