Introduction: Treatment discontinuation and treatment-free remission (TFR) emerged as the new goal of therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP). Although uncommon, some patients may still experience molecular or hematologic relapse after treatment discontinuation, even after a prolonged duration of remission. Case Presentation: In this case series, we report the outcome of 3 patients with CML-CP who were treated with tyrosine kinase inhibitors and achieved a deep molecular response for ≥8 years, but eventually experienced disease relapse after treatment discontinuation. We discuss the importance of regular monitoring after treatment discontinuation as well as future strategies to increase the chances of TFR in patients with CML-CP. Conclusion: Despite the high chances of TFR after TKI discontinuation in patients with CML-CP who remain in sustained and prolonged DMR, relapses can still occur. Regular monitoring with RT-PCR is recommended to detect any recurrence of the disease.

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