acute myeloid leukemia | Acute myeloid leukemia: symptoms, treatment and prognosis

Acute myeloid leukemia: symptoms, treatment and prognosis

Myeloid leukemia is a type of cancer of the blood or bone marrow that causes an alteration in the number of blood cells:

White blood cells (leukocytes),
Red blood cells,
Platelets.
Bone marrow produces blood cells.
Leukemia usually affects the production of white blood cells, which are the cells that fight viruses, bacteria and fungal infections to prevent infection.
The immature cells (blasts) found in the case of leukemia do not function as normal and mature cells.
Blasts are immature cells derived from:

White blood cells,
Red blood cells,
The platelets.
In case of acute myeloid leukemia, the blasts:

They continue to grow,
They clog the bone marrow and interfere with the production of normal cells.

The consequences are the difficulties:

To fight infections,
To block the bleeding,
to transport oxygen.


Acute leukemia
This proliferative disease is characterized by rapid growth of immature blood cells.

Leukemia, blood cells, red, white, plaquettesCette accumulation prevents the bone marrow from producing healthy blood cells.
Immediate treatment is necessary because of the rapid evolution of the disease and the accumulation of malignant cells that:

Penetrate the blood flow,
Diffuse to other organs.
If this pathology is not treated, the patient can die in a matter of months or even weeks.
There is a serious variant of acute leukemia, which takes the name of lightning leukemia. In that case:

The evolution is very fast,
The patient's death usually occurs in a short period of time.
Acute leukemia is characterized by:

The increase of cells in the blood,
Stopping differentiation – cells produced by the bone marrow are blasts, i.e. immature or undifferentiated cells.

Also known as acute myeloid leukemia, it occurs more frequently in adults than in children.

Indeed, studies show that LMA occurs mainly in men, rather than in women.

It was previously called acute non-lymphoblastic leukemia.

Acute lymphocytic leukemia (ALL)

This type of leukemia affects lymphoid cells (lymphocytes) that accumulate:

In the bone marrow,

In the lymph nodes and in the lymphatic tissue.

The lymphatic tissue is the immune system.

Also known as lymphoblastic leukemia, this is the most common type of leukemia in children. It also affects adults, including persons aged 65 years or older.

It is a lymphocyte cancer that is characterized by excessive production and the continuous multiplication of malignant immature white blood cells in the bone marrow. It is a cancer of the blood.

Childhood leukemia

Similar to that of adults, this leukemia can be:

Acute

Chronic.

However, in children, leukemia usually occurs in acute form.

Acute childhood leukemia is classified into 3 categories:

In the case of all, the pathology first affects the cells that produce the lymphocytes, while the LMA first touches the non-lymphocyte cells that produce:

White blood cells,

Red blood cells,

The platelets.

Hybrid leukemia is a combination of all and LMA, in which lymphocyte and non-lymphocyte stem cells are affected.

All is the most common type of childhood leukemia: it accounts for up to 70% of cases.

The remaining 30% are cases of LMA or hybrid leukemia.

A rare form called Juvenile myelomonocytic Leukemia (LMMJ), acute or chronic, occurs in infants, usually under 4 years of age.

Symptoms of myeloid leukemia acute myeloid leukemia (LMA) marrow, bone, cells, blood

LMA diffuses rapidly in the blood and bone marrow.

Symptoms of Acute myeloid leukemia

Fever

Loss of weight and loss of appetite,

Fatigue

Bone pain,

Shortness

Blue, also spontaneous type,

Frequent Infections,

Bleeding of the nose, gums and menstruation abundant in women (in case of reduction of platelets).

The Adénomégalie (swollen lymph nodes) located or disseminated is present in 14% of the cases. Massive generalized Adénomégalie is present in about 25% of patients with the M4-M5 (monocytic component) Form.

Linfonodo-Parotid-Gonfio-Leucemia-acuta-mieloideUn lymph node parotid is assigned in the image to the right.

The patient suffers from acute extra-medullary myeloid leukemia, with accumulation of neoplastic cells in the skin or in other organs.

Initial symptoms of leukemia

The first symptoms and signs of leukemia are:

Constant fatigue,

Weight loss,

Fever or chills,

Frequent infections.

Childhood leukemia Symptoms

Children may show different symptoms depending on the number of leukemic cells.

Children who suffer from this disease appear pale, weak and anemic. Here are other symptoms:

Fever;

Joint and Bone pain

swollen lymph nodes in the neck, armpits and groin;

weakness;

Fatigue and exhaustion

Loss of appetite

Petechiae (small red patches appearing under the skin following bleeding);

The spontaneous appearance of bruises;

Bleeding from the gums and nose

Shortness of breath (especially in the terminal phase of the disease);

Recurring infections.

The decrease in the number of red blood cells also causes a pallor of the skin, as well as swelling of the lymph nodes due to the excess of white blood cells in the blood.

The FAB classification of the LMA

In 1970, a group of French, American and British experts classified acute myeloid leukemia in subcategories from M0 to M7, depending on the type of cells from which leukemia developed and the maturation of these cells.

Sub-category FAB name

M0 Acute myeloid leukemia undifferentiated

M1 Acute myeloid leukemia with minimal maturation

M2 Acute myeloid leukemia with maturation

M3 Acute promyelocytic leukemia (LAP)

M4 Acute myelomonocytic leukemia with abnormal eosinophils

M5 Acute monocytic leukemia

M6 Acute erythroid leukemia

M7 Acute Mégacaryoblastique leukemia

The blasts of the M0 do not have any signs of differentiation, so they are absolutely immature.

From M1 to M3, differentiation is interrupted at different levels, the blasts of:

M1 is at a rather undifferentiated stage,

M2 are at an intermediate stage,

M3 are more differentiated.

The presence of granules is a typical sign of differentiation, in particular the granules are observed in the M2, but not in the M1.

Treatment of acute myeloid leukemia

Since there are many forms of acute myeloid leukemia, it is difficult to identify the appropriate targeted treatment.

There are approximately 200 known translocations and chromosomal mutations, but some are more common than others.

One of the most common mutations in LAM is the tandem internal duplication of 3 FMS tyrosine kinase (FLT3-ITD).

This mutation is present in about 25% of all patients who suffer from LAM and is associated with an adverse prognosis.

Source: Acute myeloid leukemia: The challenge of capturing disease variety. Löwenberg B – Hematology Am Soc Hematol Educ Program. 2008; (): 1-11.

In general, the Doctor offers therapy with different types of medications.

The treatment provides:

Chemotherapy

The combinations of Cytarabine (AraC) and anthracyclines constitute the initial treatment of acute myeloid leukemia.

AraC at high doses is today a standard treatment in patients under 60 years of age.

Source: Current and emerging therapies for acute myeloid leukemia – Robak T1, Wierzbowska A – Clin Ther. 2009; 31 Pt 2:2349-70.

Cytarabine (AraC) is effective against acute myeloid leukemia because it binds to the hENT1 receptor that is present in tumor cells.

After some chemical reactions inside the cell, this drug acts on DNA by blocking the synthesis and repair of cellular genetic material.

Dosage of chemotherapy drugs

Daunorubicin (60 or 90 mg/m2 on days 1, 2 and 3),

Idarubicin (10-12 mg/m2 on days 1, 2 and 3).

These medications should be administered at the same time as the continuous infusion of cytarabine for seven days (100 mg/m2/daily for one week).

The purpose of chemotherapy is the complete remission (RC), i.e.:

Less than 5% blasts in the sucked bone marrow sample, nucleated cells ≥ 200 (without blasts with Auer body or persistence of extra-medullary disease);

Neutrophils (ANC) > 1000/ΜL.

Platelets ≥ 100 000/μl

Tyrosine kinase 3 (FLT3) inhibitors similar to FMS

Several inhibitors of small FLT3 molecules have been developed with mixed results.

First-generation drugs include multi-kinase inhibitors such as:

Acute lymphocytic leukemia (all);

Acute myeloid leukemia (LMA);

Hybrid leukemia.

The Midostaurin,

The lestaurtinib,

The tandutinib,

The sunitinib,

The sorafenib.

Used individually, they have a limited anti-leukemia activity that shows:

Only transient reduction of blasts (immature cells) in the blood and bone marrow,

An increase in toxicity.

Differential therapy

The problem of acute myeloid leukemia is the blocking of the differentiation program, which is why it is necessary to differentiate treatment.

The treatment of immature cells is carried out with:

Retinoic acid (a derivative of vitamin A), and in particular the ATRA form (all trans retinoic acid), which is recognized by RARα receptors (α retinoic acid receptor) and the blast becomes a granulocyte,

Vitamin D3 – In this case, the blasts become monocytes.

Source: FLT3 inhibitors in AML: Are we there yet? – Sudhindra A, Smith CC – Curr Hematol Malig Rep. 2014 Jun; 9 (2): 174-85.

Allogeneic transplantation of stem cells

This is the most performed type of transplant for the treatment of LMA.

In a allogeneic transplant, stem cells come from a person other than the patient, usually a donor with a marrow compatible with that of the patient.

In AML, allogeneic transplantation is better compared to autologous transplantation (with cells of the same person).

Leukemia is a disease of the blood and bone marrow, so by entering the patient its cells there is a risk of transplanting malignant cells (leukemia).

What is the life expectancy? Prognosis in case of acute myeloid leukemia

The prognosis depends on:

Of the patient's age, over 60 years the prognosis is the worst,

Of the type of chromosomal alteration.

From 2003 to 2009, 5-year survival rates for children were as follows:

All: 91.7% for children and adolescents under 15 years of age and 92.6% for children under 5 years of age.

LMA: 64.8% for children and teenagers under 15 years of age.

Survival statistics have improved significantly over the last 50 years.

Despite significant progress in the treatment of LAM:

From 20% to 40% of patients do not get a complete remission with chemotherapy,

From 50% to 70% of patients develop a relapse within 3 years.

About 60% to 70% of adults with LAM have complete remission after medical treatment.

More than 25% of adults with LAM (about 45% of those with complete remission) survive for 3 years or more.

Remission rates in adults suffering from LMA are inversely proportional to age, with an expected remission rate of more than 65% for people under 60 years.

The data show that in older patients, the duration of remission is shorter.

Other adverse prognostic factors are:

The involvement of the central nervous system,

Systemic infection at the time of diagnosis,

The high number of white blood cells (> 100 000/mm3),

LAM caused by treatment,

Previous blood diseases.