When we talk about leukaemia, we are not talking about a single disease, but about a group of blood cancers caused by the uncontrolled proliferation of haematopoietic stem cells, called leukaemias or blasts, i.e. those still immature cells that grow to give rise to the components of our blood: white blood cells, red blood cells and platelets

Blood stem cells originate in the bone marrow, present in adults mainly in the flat bones (such as pelvis, sternum, skull, ribs, vertebrae, scapulae) and can follow 2 developmental lines

• the cells of the myeloid line give rise to white blood cells (particularly neutrophil monocytes), platelets and red blood cells;
• the cells of the lymphoid line give rise to white blood cells, also called lymphocytes.

As a result of genetic mutations and complex mechanisms, which have not yet been fully elucidated, stem cells can prematurely halt their development, or they can acquire the ability to replicate without limit and become resistant to the mechanisms of programmed cell death (apoptosis).

When this happens, immature cells invade the marrow, blood and sometimes the lymph nodes, spleen and liver and thus give rise to leukaemia.

The different types of leukaemia

One of the factors that classify the disease is its speed of progression: acute forms have a short or very short time course and also present a blockage of cell maturation, while chronic forms have a slower evolution, in which the marrow precursors’ ability to mature is nevertheless maintained, although it may be abnormal.

According to the Italian National Cancer Registry, the most frequent forms are:

• chronic lymphatic (33.5% of all leukaemias);
• acute myeloid (26.4%);
• chronic myeloid (14.1%);
• acute lymphatic (9.5%).

Data on leukaemias

Cancers affecting blood cells are much more frequent in childhood than in adulthood.

In particular, acute lymphoblastic leukaemia accounts for 75% of all leukaemias diagnosed in children up to 14 years of age, while acute myeloid leukaemia accounts for 15-20%.

In adults, on the other hand, the majority of acute leukaemias are myeloid forms, while lymphoblastic leukaemias are less frequent, around 25-30%.

Chronic leukaemias, on the other hand, are typical of adulthood, while they are rare in childhood.

Although the incidence of leukaemias is growing, with almost 8,000 new cases diagnosed in Italy, mortality is decreasing thanks to a continuous and steady improvement in treatment.

Symptoms of acute leukaemias

In the early stages, chronic leukaemias may give no symptoms because leukaemic cells interfere in a limited way with the functions of other cells.

In contrast to acute leukaemias, symptoms occur early and can worsen very quickly.

Fever, night sweats, tiredness and fatigue, headaches, bone and joint pain, weight loss, pallor, are usually associated with red blood cell deficiency, thus with a major anaemia condition.

In the case of platelet deficiency, minor haemorrhages in the oral cavity or gastrointestinal tract or spots on the skin may also appear.

In a later, but always very rapid step, deeper haemorrhages may also appear in the brain or gastrointestinal tract.

While in the case of white blood cell proliferation, there may be symptoms similar to a bad flu syndrome, such as continuous but well-tolerated fever.

Sometimes leukaemic blasts can also infiltrate organs such as the stomach, intestines, kidneys, lungs or nervous system, giving specific symptoms indicating a malfunction of the organ involved.

The most innovative treatments and therapies against leukaemia

Over the last few years, there has been a steady and progressive improvement in the prognosis of the disease for two reasons: we know more about the factors underlying these diseases, in particular the genetic mutations associated with the more aggressive forms, and can therefore proceed with transplantation in the early stages, when the patient is less compromised, has undergone fewer therapies and better results can be achieved; and a steady improvement in therapies that are combined on the basis of the characteristics of the individual patient’s disease.

Fighting leukaemia: haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation is one of the treatment options used to replace diseased cells, destroyed by high doses of chemo or radiotherapy, with healthy ones from a compatible donor.

Often the donor is a sibling or family member, but it can also be a stranger who possesses cells compatible with those of the patient.

In some cases, this approach can definitively cure leukaemia, especially in younger patients, and can be used for forms that no longer respond to chemotherapy.

This is why it is important to enrol in the bone marrow donor registry, a simple gesture that makes it possible, by taking a small amount of blood or saliva for genetic typing, to save a life in the future.

Chemotherapy and immunotherapy with CAR-T cells

In addition to transplantation, other therapies available today are chemotherapy combined with other approaches aimed at stimulating the immune system to recognise and destroy leukaemia cells, such as, for example, interferon alpha used to slow down the growth of tumour cells, or monoclonal antibodies capable of targeting leukaemia cells, promoting their destruction by the immune system.

An innovative therapeutic approach in recent years is immunotherapy with CAR-T cells, an option available for certain leukaemias that do not respond to conventional treatments.

CAR-T cells are the patient’s own T lymphocytes that are genetically modified to be equipped with the CAR molecule (chimeric antigen receptor).

Thanks to this molecule, once they are reintroduced into the patient, CAR-T cells are able to specifically recognise tumour cells and effectively attack and destroy them.

Leukaemia is precisely the first cancer to be treated with this therapeutic tool, which has been available in Italy since 2019.

Leukaemia research does not stop

Research remains the mainstay for improving the prognosis of these diseases: reducing the toxicities associated with haematopoietic stem cell transplantation and improving transplantation also from external or haploidentical donors (parents for children and vice versa), are 2 of the goals achieved in recent years.

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Source:

GSD