Acute myeloid leukemia What's this?

Acute myeloid leukemia
What's this



Acute myeloid leukemia (AML) is a disease that develops from bone marrow (myeloid) and progresses rapidly (acute). Blood cells are present in the bone marrow in the form of "precursors" and, through a path of maturation, can be differentiated into white blood cells (including lymphocytes), red blood cells, or platelets.

If in this path that leads them to become "adults" the precursors "(except those of the lymphocytes) undergo a transformation in the tumor sense, we arrive at the LMA.
How widespread

According to data from the Italian Association of Cancer Registries (AIRTUM), it is possible to estimate just over 2,000 new cases of acute myeloid leukemia every year in Italy: 1,200 among men and 900 among women.

The disease is more common in men than in women and adults over the age of 60. It is infrequent before age 45 and in our country represents 13% of leukemias among children aged 0 to 14 years.
Who is at risk

Some lifestyle factors, such as smoking, increase the risk of developing LMA, while environmental risk factors include exposure to certain chemicals such as benzene and its derivatives used in the chemical industry and in refineries. Some cancer treatments can also increase the risk: it is the case of alkylating and platinum-based drugs used for chemotherapy or radiation associated with radiotherapy.

As with other tumors, non-modifiable risk factors have also been identified for the LMA, on which it is not possible to intervene: among these we remember being a man and being over 60 years old. Finally, some genetic diseases (Fanconi anemia, Bloom syndrome, ataxia-telangiectasia, Li-Fraumeni syndrome, neurofibromatosis, etc.), some chromosomal abnormalities (Down syndrome, trisomy of chromosome 8) and certain diseases of the disease can also increase the risk. blood (chronic myeloproliferative disorders and myelodysplastic syndrome).
Types

Myeloid leukemias are subdivided, according to their cellular and molecular characteristics, into myelocytic, myelogenous or non-lymphocytic cells. Moreover, they are distinguished in primary (or de novo), that is, with primitive and secondary onset, if they arise after a previous myelodysplastic syndrome or as a consequence of exposure to toxic substances and / or chemotherapies.

In more detail, the World Health Organization published a new classification for acute myeloid leukemia in 2008:

    with recurrent genetic anomalies,
    with changes related to myelodysplasia,
    secondary to chemotherapy / radiotherapy,
    not better specified.

This classification has at least partially replaced the older Franco-American-British system (FAB), which distinguished different types of LMA indicated by the initials M0 to M7, based solely on the morphological appearance of the cells visible under a microscope.
Symptoms

Symptoms of LLA occur early and usually the diagnosis is performed shortly thereafter. Often the LLA initially manifests with non-specific symptoms such as fatigue, loss of appetite, night sweats and fever. Later on, in general, exhaustion and pallor linked to anemia, an increased risk of infections due to the reduction of normal white blood cells and frequent bleeding (also in the nose and gums) related to the lack of platelets. Systemic symptoms include widespread muscular and osteo-articular pains, a sense of general malaise and weight loss. Furthermore, if the disease has spread to other organs, the spleen, liver and lymph nodes are enlarged, and if the nervous system has also been reached, headaches and other neurological signs may occur.
Prevention



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To date, the only LMA prevention strategies are based on avoiding known risk factors when possible: quitting smoking is certainly important, as well as trying to avoid exposure to dangerous chemicals.
Diagnosis

The first step towards the diagnosis of LMA is a consultation with the doctor who will evaluate the family history and symptoms and make a careful visit to check for signs that could make you think of the disease (enlarged lymph nodes or abdominal organs, signs of bleeding). , bruises or infections, etc.). In case of suspicion, we proceed with further tests such as blood collection that allows to evaluate the number and shape of cells: in fact, leukemia causes anemia, a low number of platelets and an increase or decrease in white blood cells and the shape of cells observed at the microscope is useful to remove the last doubts and formulate a more precise diagnosis. Once the presence of leukemia has been ascertained, it is generally proceeded with a further blood or bone marrow sampling which, thanks to molecular and cytogenetic tests, allows to characterize leukemia in a finer way (presence of mutations, chromosome anomalies, etc.). Diagnostic imaging tests such as X-ray, CT, PET, ultrasound and magnetic resonance imaging are typically used to determine the presence of infections or other signs of leukemia and can help to understand how widespread the disease is.
Evolution

In general, LMA does not cause the formation of distinct tumor masses with subsequent metastases. The classification is still fundamental for the choice of treatment and to define the prognosis and is based on specific criteria, defined by the FAB systems (Franco-American-British, from the 70s) and WHO (World Health Organization, updated to 2008) described in the "Types" section of this sheet.
How to cure

The choice of the most suitable therapy for LMA depends on several factors and, firstly, on the characteristics of the disease and the characteristics of the patient.

In general, systemic chemotherapy (ie, which reaches the whole organism and is administered intravenously) remains the treatment of first choice. It begins with an induction phase that aims to eliminate the leukemic cells (blasts) present in the blood and to bring those of the bone marrow back to normal levels. Once the so-called remission is obtained, ie the absence of signs and symptoms (less than 5% of blasts in the marrow, normal blood cell counts and no clinical signs of leukemia), we move on to the consolidation phase which aims to strengthen the results obtained in the first phase, also eliminating the last remaining cancer cells. The drugs used for the induction phase are used, with different doses and timing, also for the consolidation phase and today many new chemotherapeutic agents are available and used in the experimental phase. In the case of acute promyelocytic leukemia, there is sometimes a third maintenance phase that is based on low-dose chemotherapy for months or years after the consolidation phase. Furthermore, in this subtype of leukemia, particular drugs are used, such as all-trans retinoic acid (ATRA) and arsenic trioxide, which are not used for other forms of LMA.

After consolidation therapy it is possible to proceed with a transplant of hematopoietic stem cells, capable of generating blood cells. The choice to proceed with the transplant depends on the patient (it is suitable for younger patients), the characteristics of the disease, the prognostic factors and the availability of a donor. Stem cells can be taken from the blood or bone marrow of the same patient (autologous transplantation) or a donor (allogeneic transplantation) or can derive from umbilical cord blood. Thanks to the transplantation it is possible to use higher doses of chemotherapy increasing the probability of destroying all the tumor cells and the marrow damaged by the chemotherapy will then be replaced by the one introduced with the transplant. In the elderly or in patients who do not tolerate high doses of chemotherapy, we proceed with a non-myeloablative (or reduced intensity or mini-transplant) transplant form. In this case low dose chemotherapy is used and the ability of the new transplanted cells to trigger immune reactions against tumor cells is exploited.

Other approaches to treating LMA are quite rare and ineffective: surgery has virtually no role, while radiotherapy can sometimes be used before stem cell transplantation or to reduce pain if chemotherapy does not work.

During treatment, support therapies (red blood cell transplusions and platelet concentrates or antibiotic and antifungal treatments) are also used in order to