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2463 Comparative Analysis of Flow Cytometry and Real-Time Quantitative Polymerase Chain Reaction for the Detection of Minimal Residual Disease in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia before Hematopoietic Stem Cell Transplantation

Program: Oral and Poster Abstracts
Session: 803. Emerging Diagnostic Tools and Techniques: Poster II
Hematology Disease Topics & Pathways:
Technology and Procedures, flow cytometry, molecular testing
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Xinyu Wang, MD*, Yingjun Chang*, Yanrong Liu*, Yazhen Qin*, Lanping Xu*, Yu Wang*, Xiaohui Zhang*, Xiaojun Huang, MD and Xiaosu Zhao, PhD*

Peking University People’s Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China


BackgroundThe aim of this study was to examine the value of MRD detection by multiparameter flow cytometry (MFC) and RQ-PCR before hematopoietic stem cell transplantation (HSCT) for predicting relapse and leukemia-free survival (LFS) in Philadelphia chromosome-positive ALL (Ph+ ALL).

MethodsA retrospective study (n=280) was performed. MRD was determined using multiparameter flow cytometry and RQ-PCR.

ResultsMRD 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% and 60.7% respectively. Ph+ ALL patients with MFC MRD positive (MRDpos) had a higher 3-year cumulative incidences of relapse (CIR) compared to those with MFC MRD negative (MRDneg) (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, compared to RQ-PCR MRD<1% group, patients with RQ-PCR MRD≥1% experienced higher 3-year CIR(23.1% vs. 11.4%, P = 0.032), lower LFS(53.8% vs.74.1%,P = 0.011) and OS (57.7% vs.79.1%,P = 0.009). 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%, 87.16%. When RQ-PCR MRD≥1% was used to predict recurrence, the sensitivity, specificity, PPV, and NPV were 23.0%, 88.59%, 17.15% and 91.84%, respectively. Moreover,MRD-positive status before transplantation (MFC MRDpos or RQ-PCR MRD ≥ 1%) was used to predict recurrence after transplantation, the sensitivity, specificity, PPV, and NPV were 54.29%, 73.88%, 45.7%, and 91.87%.

Conclusion:Both MFC and RQ-PCR detection of pre-transplant MRD levels can predict the prognosis of Ph+ B-ALL patients eceiving Allo-HSCT. MFC MRD positive status and RQ-PCR MRD ≥ 1% before transplantation are the risk factors for recurrence after transplantation. The combined use of the two methods can improve the sensitivity of predicting recurrence and help to better screen high-risk patients for intervention, thereby improving clinical efficacy.

Keywords: acute lymphocytic leukemia, minimal residual disease, pre-transplant MRD levels, flow cytometry, RQ-PCR, BCR/ABL, relapse

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH