Profile, diagnosis and treatment prospects for a disease that is no longer fatal but chronic

Twenty-five years ago, a diagnosis of chronic myeloid leukaemia (CML) was tantamount to a death sentence, with an average life expectancy of just 3–5 years. Today, the situation has changed radically: what was once a rapidly fatal disease has been transformed into a chronic condition that can be managed over the long term, with a life expectancy entirely comparable to that of the general population. Behind this extraordinary achievement, however, lies a clinical and human reality that remains unresolved, where the primary challenge is no longer simply to live for a long time, but to live well.

CML is a myeloproliferative neoplasm of the bone marrow stem cells, characterised by the uncontrolled proliferation of myeloid white blood cells that invade the peripheral blood. The disease is caused by a very specific acquired genetic abnormality: the so-called Philadelphia chromosome (Ph), resulting from a reciprocal translocation of genetic material between chromosomes 9 and 22. This abnormality leads to the formation of the BCR-ABL1 fusion gene, which synthesises a protein with abnormal and unceasing tyrosine kinase activity, responsible for uncontrolled cell proliferation and the inhibition of normal programmed cell death processes.

Formally recognised as a rare cancer, CML accounts for between 15 per cent and 20 per cent of all leukaemias affecting adults. Epidemiological data show an annual incidence of 1–2 new cases per 100,000 people, which in Italia translates to approximately 800–1,250 new diagnoses each year. According to estimates, around 9,000 people in Italy are currently living with the condition. Although it can occur at any age, the disease predominantly affects older age groups, with a median age at diagnosis of between 57 and 60 years and a slight prevalence among men.

CML often progresses very gradually: in its early stages, the disease is so slow and silent that many people experience no symptoms for months or even years. It is no coincidence that the condition is frequently discovered purely by chance, during a routine blood test which reveals a sharp and unexpected rise in white blood cell count, accompanied by immature or abnormal blood cells. When these warning signs do appear, they are easily mistaken for a period of simple stress or temporary tiredness: a weakness that never goes away, a slight fever in the evening, night sweats and unexplained weight loss. In about one in two patients, an enlarged spleen (known as splenomegaly) is also found, which can cause a feeling of heaviness in the abdomen. Recognising the disease in time is crucial: if left untreated, it risks progressing rapidly towards what is known as a blast crisis – an aggressive phase very similar to acute leukaemia – where conventional treatments struggle to take effect and the average survival rate plummets to just 12 months.

The real breakthrough in treatment began in 2001, when the first tyrosine kinase inhibitor (TKI) was introduced into clinical practice. Unlike traditional chemotherapy, these drugs act like tailor-made keys capable of shutting down the engine of tumour proliferation by blocking the abnormal BCR-ABL protein. Over the years, the arrival of second- and third-generation molecules has made it possible to refine the strategy, adapting treatment over time thanks to simple molecular blood tests that constantly monitor the activity of the disease. Yet this scientific success story is not yet a completely closed chapter. Clinical data show, in fact, that not all treatment journeys get off to a good start. A poor start risks compromising the course of treatment that follows: when patients are forced to switch therapy, between 60% and 72% do not achieve optimal control two years after starting second-line treatment.