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Monitoring MRD with flow cytometry: an effective method to predict relapse for ALL patients after allogeneic hematopoietic stem cell transplantation

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Abstract

This study evaluated the prognostic value of minimal residual disease (MRD) monitoring by four-color flow cytometry (FCM) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). MRD was examined with four-color FCM at different time points in 139 patients (including pediatric and adult patients) with ALL after allo-HSCT. Real-time quantitative polymerase chain reaction (RQ-PCR) was applied to evaluate the MRD of Philadelphia chromosome-positive ALL (Ph+ ALL) patients. Patients who were FCM-positive (FCM+) after transplantation had a lower event-free survival (EFS) of 0.54 and a higher cumulative incidence of relapse (CIR) of 0.54 compared to an EFS of 0.80 and a CIR of 0.08 in FCM-negative (FCM−) patients (EFS, p < 0.001; CIR, p < 0.001). Similar results were obtained in high-risk patients and Ph+ ALL patients. Moreover, a FCM+ status after the second month post-HSCT (defined as MRD positive) proved to be a predictor of leukemia relapse. Multivariate analysis for EFS, OS and CIR showed that MRD status after transplantation was an independent prognostic factor (p < 0.001, p = 0.013, and p < 0.001, respectively). A good correlation was found between the MRD results of FCM and RQ-PCR (n = 126 pairs, Spearman r = 0.8139, p < 0.001). MRD monitoring by four-color FCM post-transplantation is an important tool for relapse prediction in ALL patients. Prompt and appropriate pre-emptive anti-leukemia treatment could be considered based on the status of MRD after HSCT.

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Acknowledgments

This work was supported by the National Outstanding Young Scientist’s Foundation of China (grant No. 30725038), Program for Innovative Research Team in University (grant No. IRT0702) and Leading Program of Clinical Faculty accredited by the Ministry of Health of China. The authors reported no potential conflicts of interest.

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, No 11 Xizhimen South Street, Beijing, 100044, People’s Republic of China

    Xiao-Su Zhao, Yan-Rong Liu, Hong-Hu Zhu, Lan-Ping Xu, Dai-Hong Liu, Kai-Yan Liu & Xiao-Jun Huang

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  1. Xiao-Su Zhao
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  2. Yan-Rong Liu
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Correspondence to Xiao-Jun Huang.

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Xiao-Su Zhao and Yan-Rong Liu contributed equally to the manuscript.

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Zhao, XS., Liu, YR., Zhu, HH. et al. Monitoring MRD with flow cytometry: an effective method to predict relapse for ALL patients after allogeneic hematopoietic stem cell transplantation. Ann Hematol 91, 183–192 (2012). https://doi.org/10.1007/s00277-011-1285-1

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