Leukemia

The leukemia or leucosis is a Cancer affecting the cells of the Sang called also liquid tumor, to distinguish from the lymphomas which are also tumors of cells of blood but developing in the secondary lymphoid surfaces. At the 19th century, this term indicated only one Maladie mortal. Blood extracts from the patients reached by this disease was of aspect blanchâtre. One distinguishes today from many types of leukemias which require each one a specific treatment.

In 1847, Rudolf Virchow, a doctor German histologist , was one of the first to describe leukemia. This disease begins in the osseous Moelle. The leukaemic cells behave in an abnormal way because of a modification of their genome with an accumulation, on the level of their DNA, Mutation S acquired which allow the transformation of the cell.

The Original cells of osseous marrow daily produce billion red globules, white globules and plate S.

Leukemia is characterized by an abnormal and excessive proliferation precursors of the white globules, blocked at a stage of differentiation, which end up invading osseous marrow completely then blood. Settle then a medullary table of Insuffisance with insufficient production of red globules (source of Anémie), of normal white globules, Polynucléaire S mainly, (Leuconeutropénie, source of serious infections) and of plates (Thrombopénie, source of caused or spontaneous hemorrhages).

The leukaemic cells can also invade other bodies like the lymphatic ganglia, the Rate, the Foie, the Testicule S or the central Nervous system.

Certain hematologists advance the idea that progress as regards leukemia is done more quickly than for other cancers, from the accessibility to the blood cells (by a blood test), thus accelerating research (see progress as regards leukemia).

Four types of leukemias

Leukemia clinically and is pathologically divided into two: acute leukemia and chronic . And divided according to the origin of the tumoral cells: lymphoid cells and cells myéloïdes.

• the acute leukemia is characterized by the fast of immature cells of blood, abnormal histologically and ineffective proliferation. Acute leukemias appear in the child and the young adult, an immediate processing must be carried out to avoid the diffusion of these cells to all blood like with the bodies.

• the chronic leukemia , here the cancer cells are more mature, although always abnormal and passing in blood, the evolution is done over months at years. The tumoral cells are created in greater number than the normal but at the beginning sufficiently slightly not to involve the death. Chronic leukemias arrive mainly in the elderly. This type of leukemia can be treated more tardily thus making it possible to see during an amount of time how evolves/moves and how the disease for treating best is made.

By combining two classifications one obtains the following table:

The most current forms in the adult are the LAM and LLC, whereas in the child the LAL prevail.

Inside even of these types, there exist other categories making it possible to have a treatment more targeted. They are classifications FAB and WHO.

Classification FAB of acute leukemias

At the beginning of the Years 1970, an international group made up of French, American and British researchers worked on a new classification of acute leukemias by examining hundreds of medical files of leukaemic patients. It resulted from it classification free-américano-British, always used today to classify acute leukemias.

This classification recognized 3 various kinds of lymphoblastic acute Leucémie (LAL): L1, L2 and L3, and 7 sub-types of myeloblastic acute Leukemia (LAM): M1, m2, m3, M4 and M4Eo, M5 and M6. Secondarily the types M0 and M7 were added. On the therapeutic level the LAL L1 and L2 are treated in the same protocols; the L3 type, also called Leukemia of Burkitt, concerns a different treatment.

For the LAM, the type m3 (acute Leukemia promyélocytaire) profited from recent progress (use of the acid all-trans rétinoïque or Trétinoïne and of arsenic salts) and is treated according to specific protocols; the other sub-types of LAM treat in an identical way.

Classification FAB currently tends to being replaced by a new classification worked out under the aegis of WHO (WHO classification).

The characterization of the leukaemic cells is supplemented by the study:

• of the immunophénotype: research of the expression of certain markers on the surface of the leukaemic cells. For the LAL that makes it possible to determine nature B or T of the proliferation;

• of the chromosomic chart: search for chromosomal anomalies acquired of the leukaemic cells. Some of these anomalies are specific of a particular sub-type of leukemia; others have a prognostic value;
• of their DNA and of its transcribed (ARN): various types of examinations of molecular biology will come to supplement the chromosomic chart and to seek also certain chromosomal anomalies. In the near future also will be analyzed the whole of transcribed ARN of the leukaemic cells aimed diagnostic and prognostic.

Chronic proliferations of myéloïde type

The principal one is the chronic Leucémie myéloïde (LMC) characterized by an abnormal chromosome identified by the study of the chromosomic chart of the leukaemic cells, the Chromosome of Philadelphia (Ph1). It is due to a chromosomal translocation between the chromosomes 9 and 22.

The other types are the chronic Leucémie myélomonocytaire (LMMC), initially classified by the FAB in the group of the Myélodysplasie S, and the shape of the child, very rare, the youthful Leucémie myélomonocytaire.

Chronic lymphoid proliferations

Most frequent chronic lymphoid Leucémie is the (LLC) which is in general a proliferation B. It exists other lymphoid proliferations: for example, prolymphocytaire T of Galton, fungal Mycosis, with lymphocytes T suppressors, etc). The LLC are sometimes classified, not without reason, among the Lymphome S.

• See: gene BTG1.

Myeloblastic acute leukemias

Myeloblastic acute leukemias or LAM:

• LAM 0: undifferentiated

• LAM 1: myeloblastic without differentiation
• LAM 2: myeloblastic with differentiation
• LAM 3: promyélocytaire
• LAM 4: myélomonocytaire
• LAM 4Eo : myélomonocytaire with éosinophilie
• LAM 5: monoblastic (without differentiation: M5a, with differentiation: M5b)
• LAM 6: erythroblastic or erythroleucemy
• LAM 7: megacaryoblastic

Acute lymphoblastic leukemias

Lymphoblastic acute leukemias or LAL:

• LAL 1

• LAL 2
• LAL 3 or leukemia of Burkitt

The L3 type always corresponds to proliferations B. the L1 types and L2 can correspond to pre-B proliferations, with variable degrees of differentiation, or with proliferations T.

Other leukemias

• Tricholeucémie for example.

At which a leukemia can it be declared?

Nobody is safe from leukemia: everyone can have a leukemia, almost birth until the 4th age. However, certain types of leukemias develop at a certain type of patients:

• LAL : most frequent of leukemias of the child. The peak of frequency is observed between 2 and 5 years, but all the ages are concerned. In the adult, it is rarer than the LAM;

• LAM: rare in the child, it is most frequent of acute leukemias in the adult;
• LMC: leukemia of the adult, rare in the child;
• LLC: only at the 3rd age or the 4th age, exceptionally as from 50 years.

There is no notable difference of incidence between the men and the women.

There exist certain unanimously recognized risk factors:

• previous of Radiotherapy or Chemotherapy for another cancer;

• accidental exposure to the Radioactivity;
• exposure to chemicals like the Benzene, hydrocarbons aromatic, some Pesticide S and Manure;
• certain genetic anomalies like the Trisomy 21 (leukemias answering generally well the treatments).
• exposure to the X-rays before the birth

• myéloprolifératives hematologic diseases: Polyglobulie essential or Maladie of Be occupied, Myélofibrose (fibroblasts in proliferation), aplastic anemias (much is in fact only leukemias) while a chronic leukemia is often transformed into acute leukemia.

• causes unknown (9/10)

On the other hand, the magnetic fields (close to the electric lines with high-tension, for example) do not seem to be providers of leukemias, even if this always is very discussed while at the same time there exist strong biological arguments in favor of their harmlessness (as regards leukemias at least).

Treatments

The treatment is variable according to the type of leukemia:

- acute leukemias are treated by a intensive Chimiothérapie which generally requires a rather long hospitalization. The goal is to destroy the abnormal cells (the blastes ), but the “normal” cells, in particular some of enter they (cells of osseous marrow, the scalp, the digestive tract), are also sensitive there. After an intensive cure, the patient, in particular, cannot renew any more only the cells of his blood and his immune system: it is said that the patient is then in phase of aplasia ; during this phase it needs many complementary care and in particular a support Transfusionnel. The first cure is called cure of induction; then come from the cures of consolidation and, for certain leukemias, a treatment of maintenance. An irradiation of brain is necessary in certain cases. A Clerc's Office of marrow can be indicated in certain types and for the forms having the most severe forecast; a Clerc's Office is also generally indicated in the event of relapse. The total forecast is variable according to the age and the type of leukemia with chances of cure which are for the LAL of the child of 80%. - the LAM3 is treated by an association of chemotherapy and agents differentiating: acid all-trans rétinoïque and arsenic salts. The forecast is good with chances of cure higher than 70%.

- the LMC is currently treated (2006) in first intention by a drug, the imatinib, which acts specifically on the leukaemic cells and which revolutionized the assumption of responsibility of this type of leukemia. The other therapeutic options are other drugs (hydroxyurée, interféron, aracytine…) and grafts it allogenic marrow.

- the LLC, which has an evolution generally very slow, has a very variable treatment according to the evolutionary stage and the age of the patient.

Progress as regards leukemia

According to a conference of the professor Laurent Degos (service of hematology, Hospital Saint-Louis in Paris) with the Foundation for the medical research, progress as regards leukemia is faster than for the other shapes of cancer. One of the reasons is related to the facility to test the effect of the drugs: “it is definitely easier indeed to multiply the blood samples or medullary to carry out punctures or biopsies of tumors of the lung or liver. Today (2004) one lays out even of products known as differentiating which make it possible to standardize the behavior of a leukaemic cell. The best example is the treatment of the LAM3 by the rétinoïque all-trans acid. The preventive role of these differentiating drugs is discussed. Without strictly speaking constituting a “vaccination” against leukemias, they would represent a kind of functional equivalent of it”.