Chronic myeloid leukaemia (CML) is a cancerous disease of the bone marrow characterised by an uncontrolled increase in the production of some of the cells it produces.

CML accounts for around 20% of all leukaemias, although it must be considered an infrequent disease, affecting approximately one person in every 100,000. The average age of patients when the disease appears is 56, its appearance during childhood being very infrequent.

The disease is included within a group of diseases known as myeloproliferative neoplasms, the common characteristic of which is their slow evolution.

In general it is diagnosed during an asymptomatic, and not very aggressive, stage of the disease called the chronic stage. Until the arrival of the drugs that are now used, the natural evolution of the disease was to remain in this chronic phase for a period of 3 to 5 years, after which the disease progressed to an accelerated phase, and then to a blastic phase. With the presence of these accelerated and blastic phases the disease is considered to have reached the most advanced stages, now being very similar to an acute leukaemia and consequently having a very poor prognosis. Fortunately, thanks to the treatments available, the probability of progression is less than 10%.

The most usual manner in which the disease presents itself is through the chance discovery of an alteration during a blood test. Such an alteration usually consists in a marked increase in the number of leukocytes (white blood cells) and/or platelets. Around 30% of patients with such alterations may suffer from generalised tiredness, weight loss, perspiration, bone pain, bleeding, repetitive infections, or abdominal problems resulting from an increase in the size of the spleen (splenomegaly).

Upon suspicion of the disease as a result of such a test a meticulous study must be made of the patient's blood and bone marrow to confirm the presence of the disease. Diagnosis is confirmed after the detection of the presence of a chromosome called the Philadelphia chromosome (named for the city in which it was discovered). This chromosome is usually studied by means of bone marrow puncture, aspiration and biopsy. As a complementary diagnosis, and one which will later be of use for evaluating the patient's response to treatment, an oncogene called BCR-ABL must be found (this test can usually be performed through a blood test, the blood being extracted in the usual way).

Present day treatment for CML consists of the administration of drugs called tyrosine kinase inhibitors (TKI) which, in principle, must be taken indefinitely. All TKIs are taken orally and have a very good toxicity profile.

Imatinib was the first drug to be approved for this disorder, being very effective and having an excellent safety profile. Nilotinib, dasatinib and bosutinib are the so-called 'second generation' TKIs, ponatinib is generally considered to be a 'third generation' inhibitor.

Both nilotinib and dasatinib are indicated for newly-diagnosed patients, and for patients for whom an insufficient level of control is achieved after treatment with imatinib (something that can happen with up to 40% of patients). Bosutinib and ponatinib are approved for patients who do not respond adequately to a second generation TKI. A small percentage of patients may develop a specific mutation called T315I, which confers resistance both to imatinib and second generation TKIs, making it essential to pursue treatment with ponatinib.

At the present time in Spain there is a generic imatinib on the market, produced by various pharmaceutical companies. All of them have demonstrated an adequate bioequivalence with the original brand (Glivec®) at a much reduced price. Since the beginning of 2017 almost all patients treated with imatinib are treated with one of the generic drugs available.

A bone marrow transplant, considered for many years to be the treatment of choice for most CML patients, is now reserved for patients who fail to respond to treatment with TKIs, something that occurs in less than 10% of cases.

There has been a radical change in the prognosis for CML over recent years. After the arrival of TKIs, CML has changed from being a disease with a life expectancy of just 5 years for patients who are not candidates for a bone marrow transplant, to one with a life expectancy similar to that of the general population for those patients diagnosed during the chronic stage, (which is the case with the great majority of CML patients). At the present time, global survival rates for the disease are around 90%, most deaths occurring for reasons not related to the disease.

Nevertheless, there are some circumstances (the most important factor being the stage of the disease) which affect the prognosis and which must be evaluated by doctors in order to choose the most appropriate treatment.

For more quality information about chronic myeloid leukaemia you can consult the following websites:

 

• What is Chronic Myeloid leukaemia. American Cancer Society

• Chronic Myeloid leukaemia. Leukemia and Lymphoma Society

There are other resources and links of interest that may be of use to adult acute myeloid leukaemia patients:

 

• Bone marrow transplant guide. Fundación Josep Carreras

• Graft-versus-host disease. Leukaemia and Lymphoma Society

• Fertility and treatment information. Leukaemia and Lymphoma Society