Journal of Shanghai Jiao Tong University (Medical Science) ›› 2022, Vol. 42 ›› Issue (10): 1413-1419.doi: 10.3969/j.issn.1674-8115.2022.10.006

• Clinical research • Previous Articles    

Treatment-free remission after imatinib discontinuation in patients with chronic myeloid leukemia

XU Tianxue1(), QIAN Ying1, LIU Zhanyun2, CAI Gang1, WU Yingli3, LI Junmin1, SHEN Zhixiang1, ZHOU Li1()   

  1. 1.Shanghai Institute of Hematology, Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    2.Department of Hematology, Shanghai Beizhan Hospital, Shanghai 200070, China
    3.Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
  • Received:2022-06-14 Accepted:2022-09-18 Online:2022-10-28 Published:2022-12-02
  • Contact: ZHOU Li;
  • Supported by:
    National Natural Science Foundation of China(81570112)


Objective ·To analyze the outcomes of treatment-free remission (TFR) after imatinib discontinuation in patients with chronic myeloid leukemia in chronic phase (CML-CP) who meet the criteria for TFR and are willing to monitor the disease regularly, the prognostic factors and the application of droplet digital polymerase chain reaction (ddPCR) technique in monitoring TFR. Methods ·The patients with CML-CP enrolled in this study were monitored regularly after imatinib discontinuation. Molecular response and relapse were analyzed by quantitative polymerase chain reaction (QPCR) for detection of BCR-ABL transcripts. The lymphocytes subsets pre- and post-imatinib discontinuation were evaluated by flow cytometry. ddPCR was used to detect BCR-ABL and the predictive role in TFR was analyzed. Results ·① Forty-two CML-CP patients who met the criteria for TFR were assessed. With median follow-up time 41(5?93) months, 32 (76.2%) patients maintained TFR.The estimated TFR rate by 12, 24 and 48 months were 85.1%, 75.1% and 70.1%, respectively. Median TFR duration was 41 (2?93) months. The most common adverse event post-discontinuation was musculoskeletal pain of grade Ⅰ?Ⅱ (31.0%). Eight patients achieved deep molecular response (DMR) after restart of imatinib. ②58.3% of patients with continuous positive ddPCR developed molecular relapse after imatinib discontinuation, while none relapsed in those with negative detection (P<0.01). ③ The percentage of CD8+CD28- cells pre-discontinuation was lower, while the percentage of CD4+CD25+ cells post-discontinuation was higher in relapsed patients than that in TFR patients (6.2% vs 12.6%, P=0.026; 3.2% vs 2.1%, P=0.021). Conclusion ·CML-CP patients who meet the criteria of TFR may successfully maintain TFR after TKI discontinuation. ddPCR may help to predict the outcome of TFR and detect the molecular relapse earlier. Immune regulation by different T cell subsets may play a role in TFR duration to prevent relapse of disease.

Key words: treatment-free remission (TFR), imatinib, prognostic factor, chronic myeloid leukemia (CML), droplet digital polymerase chain reaction (ddPCR), lymphocyte subset

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