Chronic Myeloid Leukaemia and Allogeneic Transplantation: From Access to Monitoring—25 Years of Progress for Every Patient with CML

World CML Day - A change driven by targeted treatment

Few cancers illustrate the progress of modern medicine as clearly as chronic myeloid leukaemia (CML). The discovery of the Philadelphia chromosome and the BCR::ABL1 fusion gene led to targeted treatments that have transformed CML from a potentially fatal disease into a condition that, for most patients, can be controlled. Today, patients diagnosed with chronic-phase CML (CP-CML) are treated with tyrosine kinase inhibitors (TKIs), while allogeneic haematopoietic cell transplantation (allo-HCT) is reserved for selected patients with resistant or advanced disease.

CML is caused by the BCR::ABL1 fusion gene, which produces an abnormal protein that continuously signals blood cells to proliferate. TKIs block this abnormal signal. Imatinib was the first major breakthrough, followed by several more potent TKIs. The treatment landscape has broadened further with the advent of agents that bind to the myristoyl pocket of BCR::ABL1.

In clinical practice, treatment decisions should consider not only molecular response but also adverse effects, age, cardiovascular and other comorbidities, and the mutational profile, among other factors. A personalised approach is therefore the standard of care in CML, as reflected in the 2025 European LeukemiaNet recommendations. Another major achievement is treatment-free remission (TFR). Some patients who achieve a stable, deep molecular response can discontinue their TKI while remaining in remission. This approach requires regular BCR::ABL1 monitoring because molecular relapse can occur, but it has allowed many patients to live without continuous medication while maintaining a stable molecular response.

Allo-HCT is not the first-line treatment for most patients with newly diagnosed CML. Transplantation can cure CML, but it is an intensive therapy associated with potentially serious complications, including infections and graft-versus-host disease (GvHD). Allo-HCT is therefore recommended when CML becomes resistant to several TKIs, when the disease progresses to an advanced phase, or when none of the available TKIs is tolerated. Current data suggest that transplantation is associated with better outcomes when performed during the first chronic phase of CML; early referral to a transplant centre is therefore important for selected patients.

EBMT research and the future

Transplantation is not necessarily the end of treatment. After allo-HCT, patients are monitored closely for molecular recurrence. TKIs can be used after transplantation, as can donor lymphocyte infusion (DLI). DLI involves administering lymphocytes from the original donor to strengthen the graft-versus-leukaemia effect and can be particularly useful for relapse that does not respond adequately to TKIs.

Because evidence is limited on when to start a TKI after transplantation, which TKI to choose, how long treatment should continue, and when DLI should be used, a recent EBMT survey provided an important overview of current real-world practice. Led by Dr Kanellopoulos on behalf of the EBMT Chronic Malignancies Working Party (CMWP), the survey collected responses from transplant centres across Europe. It found that TKI maintenance is widely used, with duration generally guided by molecular response. For molecular relapse, TKIs are generally preferred to DLI, while DLI remains an important option for patients with CP-CML whose relapse is resistant to TKI therapy. The survey therefore highlights an important message: there is still no single post-transplant strategy that is appropriate for every patient.

To address this evidence gap, Dr de Lavallade is leading an EBMT expert-consensus initiative focused specifically on the management of CML after allo-HCT. The project uses a Delphi-style methodology, bringing together experienced CML and transplantation specialists to seek consensus on practical clinical scenarios for which prospective evidence is limited.

A recent study by the CML Subcommittee of the CMWP showed that outcomes for patients with an HLA-identical sibling donor are similar to those for patients undergoing transplantation with alternative donor strategies. Another EBMT study showed that post-transplant cyclophosphamide is an appropriate form of GvHD prophylaxis for patients undergoing allo-HCT from unrelated or mismatched related donors, further expanding knowledge of donor options for patients who need transplantation. The CML Subcommittee is also investigating the role of a second transplantation in patients who relapse after a first allo-HCT, as well as outcomes among patients who discontinue a TKI initiated after transplantation.

The future of CML will probably not be defined by a single new drug or procedure. Instead, the field is moving towards individualised treatment pathways. For one patient, the goal may be a deep molecular response followed by treatment-free remission. For another, several changes in TKI therapy may be necessary. For a patient with resistant or advanced CML, the priority may be to achieve a response before allo-HCT.

On World CML Day, the progress made over the past 25 years is worth celebrating. However, the next goal is equally important: not simply to help people with CML live longer, but to help more of them live well, with a lower treatment burden and, whenever possible, without detectable disease or continuous therapy.

References

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