acute lymphoblastic leukemia. What's this?

Acute lymphoblastic leukemia
What's this



Acute lymphoblastic leukemia (LLA) is a haematological tumor that originates from lymphocytes - a particular type of white blood cells - in the bone marrow and is characterized by an accumulation of these cells in the blood, bone marrow and other organs. The term "acute" indicates that the disease progresses rapidly.

Lymphocytes are cells of the immune system that monitor the body and activate defenses against microorganisms or cancer cells. They are distinguished in B or T based on the type of response they are able to activate.

In the LLA a B or T lymphocyte undergoes a tumor transformation: the maturation processes leading to the "adult" lymphocyte become blocked and the cell begins to reproduce more rapidly invading the blood and reaching the lymph nodes, the spleen, the liver and the central nervous system.
How widespread

The LLA is a relatively rare disease: in Italy there are about 1.6 cases per 100,000 men and 1.2 cases per 100,000 women, that is about 450 new cases every year among men and 320 among women.

However, LLA is the most common cancer in children, in fact it represents 80% of leukemia and about 25% of all cancers diagnosed between 0 and 14 years. The incidence reaches the peak between 2 and 5 years and then decreases with increasing age, up to a minimum after 29 years (50% of all cases are diagnosed within 29 years).
Who is at risk

There are few known risk factors for the LLA. Among the environmental ones we can mention radiation exposure (also for medical treatments such as radiotherapy) and certain chemical substances such as benzene, used in refineries and chemical industries and contained for example in some pesticides and in cigarette smoke. Among the non-modifiable factors, pediatric age and male sex increase the risk. There is no evidence that the disease is transmissible by inheritance, even if the risk increases in the case of an identical twin brother affected by LLA and following some inherited syndromes related to genetic abnormalities (Down syndromes, Klinefelter and Bloom Fanconi anemia, ataxia-telangiectasia, neurofibromatosis).
Types

The LLA is classified according to the cellular and molecular characteristics of lymphocytes and this classification is useful to better define prognosis and therapeutic pathway.

In the past, the classification of the Franco-American-British group (FAB) was the most widely used and distinguished 3 subtypes of LLA (L1, L2, L3) solely on the basis of the morphological characteristics of tumor cells. Today we use a classification, reviewed by the World Health Organization (WHO) in 2008, which takes into account both the type of lymphocyte of origin (B or T), and the degree of maturation of leukemic cells:

    LLA B: which originates from B lymphocytes
        Acute lymphoid leukemia B not otherwise specified (NAS)
        Acute B lymphoid leukemia with recurrent genetic abnormalities (further subdivided into subtypes depending on the present anomaly)
    LLA T: which originates from T lymphocytes

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

It is not possible to define prevention strategies for the LLA since the causes of the disease are not known in detail. The only useful recommendation is to avoid, as far as possible, exposure to radiation and harmful chemicals such as benzene.


Diagnosis

A complete medical examination is the mandatory starting point for a diagnosis of LLA. The doctor will evaluate the family history, symptoms and clinical signs (for example organs and swollen lymph nodes) and will eventually decide to require in-depth examinations. A simple sampling of venous blood allows to evaluate the number and appearance of blood cells to get an initial indication of the possible presence of the disease. To better define the diagnosis we proceed with other tests (carried out not only on the peripheral blood also on the bone marrow) to characterize the tumor cells from a genetic-molecular point of view and then move on to the so-called diagnostic imaging (CT, magnetic resonance, X-rays and ultrasound), useful to understand how much and where the disease has spread and to determine the presence of other problems related to leukemia, such as some infections. The examination of the liquor taken by means of rachicentesis (lumbar puncture) serves instead to check whether the disease has also reached the central nervous system.
Evolution

A further classification of the disease can be made based on the evolution of the disease after treatment:

    Disease in remission:
        complete: there are no signs of disease and the count of blasts (immature cells) in the bone marrow is less than 5%;
        complete molecular: not even with the most modern molecular investigation techniques are signs of disease.
    Minimum residual disease: the disease is only visible with modern investigation techniques, but not with standard laboratory tests.
    Active disease: there are signs of the disease during treatment or is back (recurrence) after therapy.

How to cure

The choice of treatment of LLA depends on the characteristics of the patient and the disease, but in general the therapy must be started immediately after the diagnosis given the acute character of this leukemia.

Chemotherapy is one of the main treatments for LLA: the type of drug and the doses are defined case by case after carefully evaluating many factors. In children, for example, more intensive regimens are often used, but in general the chemotherapy pathway can be subdivided into 4 phases with a total duration of about 2 years:

    Induction: to eliminate cancer cells from blood and bone marrow in order to achieve complete remission. This phase lasts 1 month or so.
    Consolidation: to strengthen the results obtained in the induction phase. In this phase, which lasts a few months, high-dose chemotherapy is used.
    Re-induction: based on the same drugs of induction, used according to different schemes.
    Maintenance: this phase lasts just over a year and uses drugs such as 6-mercaptopurine and methotrexate.

During all phases of chemotherapy it is necessary to carry out the treatment of prophylaxis of the eventual LLA at the level of the central nervous system, which consists in the administration of chemotherapy directly in the cerebrospinal fluid through lumbar punctures.

In the most difficult cases (children, high-risk patients, patients who do not respond to induction chemotherapy or patients experiencing recurrence shortly after treatment) it is also possible to carry out a haematopoietic stem cell transplant. The transplant allows to replace the diseased cells of the marrow (which are destroyed by radiation or chemotherapy at very high doses) with healthy cells that will then give rise to completely normal blood cells. Generally, in the ALL it is preferred the allogeneic transplantation (from a donor different from the patient) of stem cells that must come from a compatible family member or from a non-blood related high affinity donor.

In recent years, so-called smart drugs have also shown promising results in the treatment of LLA. In particular, the drug Imatinib has proved effective against the disease characterized by the Philadelphia chromosome, born from the anomalous fusion of parts of chromosomes 9 and 22 and typical of the more advanced age. This chromosomal anomaly gives rise to a gene called BCR-ABL which represents the specific target against which imatinib and the drugs of its own family act.



Surgery has virtually no role in the treatment of LLA. Radiotherapy, on the other hand, can be used to target cancer cells in the central nervous system to reduce pain in cases that do not respond to chemotherapy and as a treatment that precedes stem cell transplantation.