Patient education

Before attempting to achieve TFR, patients need to be fully informed about and understand the risks and benefits. They should understand that a molecular relapse (a significant increase in BCR–ABL1 transcripts, usually above MR3) is often a precursor to haematological relapse, when cells proliferate abnormally. They must therefore be prepared to attend regular monitoring and appointments so that molecular relapse can be identified and treatment restarted to avoid full haematological relapse. 

TFR may cause anxiety about the risk of haematological relapse by withdrawing a treatment that a patient knows works well. Indeed, an Italian survey of over 1100 patients reported that nearly 50% had such concerns. Not all patients will want to stop treatment, and many will prefer to manage on treatment with minimal side effects.

Patients should be aware that about half of those who stop treatment are likely to have a molecular relapse within the first year and will have to restart treatment. However, molecular relapse does not mean that the TKI has failed, only that it needs to be used for longer. Many TFR trials have shown that patients usually respond to the TKI that they initially achieved a deep molecular remission with. Furthermore, patients undergoing TFR may go into a blast crisis, whereupon achieving a second remission with just TKI therapy is unlikely. Indeed, one patient who underwent TFR in the A-STIM trial experienced a lymphoid blast crisis.

It is important for patients to understand that staying in deep molecular remission does not necessarily mean that they are cured, as CML stem cells are particularly hard to eradicate and may survive quiescently for many months. Indeed, trials have reported the occasional late relapse at 18–24 months of TFR.