Chronic Leukemia myéloïde

The chronic leukemia myéloïde ( LMC ) is a monoclonal proliferation myéloïde without blocking of maturation prevailing on the granulous line at the medullary and splenic level. It belongs to the 4 large syndromes myéloprolifératifs:

the Maladie of Be occupied
the chronic Leucémie myéloïde
the essential Thrombocytémie
the primitive Splénomégalie myéloïde or myélofibrose

This disease touches especially the adult between 30 and 50 years and is supported by the exposure to benzene and the ionizing rays. It is one of the rarest leukemias with by order of frequency:

chronic lymphoid Leukemia → acute leukemia → chronic leukemia myéloïde → leukemia with tricholeucocytes.

Physiopathology

Clinical symptoms

The beginning is insidious and certain cases are fortuitously discovered at the time of a Hémogramme of routine at subjects apparently quite bearing.

1) general Symptoms

The general state is well preserved at the beginning. The fever is absent or is reduced to Fébricule S. Pourtant the patient tests tiredness, sweats, inappétence, sometimes of the Dyspnée. Certain subjects can at the being beginning suspectés of Hyperthyroïdie: one indeed finds a metabolism basal increased, but it is in consequence of the leukaemic proliferation (hypermetabolism of all the states neoplasic S).

2) Symptoms in connection with the blood anomaly

The Anemia and the tendency to Infection S generally miss during the first months of the evolution because the white globules are functional. A little more often one notes a tendency to Hémorragie S (gingival hemorrhages, épistaxis, Purpura, hemorrhages at the time of dental avulsions).

3) Symptoms in connection with the development of leukaemic fabric

a) The Rate is large: it reaches sometimes the right iliaque pit. It is hard and painless except if there exists Périsplénite. In this case one can perceive a friction with palpating or the sounding. The Splénomégalie often appears by gravity with the épigastre or the left hypochondre, sometimes by sharp pains in the event of périsplénite.

b) The lymphatic ganglia are not hypertrophied in the majority of the cases. The forms with Adénopathie S are generally regarded as low registers.

c) The Foie is often a little increased volume, at least at the end.

d) The Os can be painful, spontaneously or with the pressure.

Tests of laboratory

Hémogramme

the white Globules usually vairent between 100 000 and 300 000 per mm ³. Their number can however be much higher, and reach the million: it is in these cases, where the sedimentation of blood out of tube shows a thick leucocytic layer creamy between the sediment érythrocytaire and lay down it plasma, which the disease deserves really the name of leukemia (=" blood blanc") that Virchow gave him. The forms sub- and aleucemic of the chronic myélose are rare. From the qualitative point of view, these G.B are primarily represented by ripe Granulocyte S, mainly of the Neutrophile S (50-70%). The eosinophilic S and the Basophile S are also very numerous. The remainder of the white population of blood is represented by the immediate precursors of the granulocytes: Métamyélocyte S, Myélocyte S and Promyélocyte S, especially neutrophiles. The Myéloblaste S are very few (1-5%). Their appearance of number signs the beginning of the acute transformation.
red Globules: anemia null or is moderated, at least at the beginning. One can find some érythroblaste S. At the final period anemia becomes serious.
Plate S: at the beginning the number of plates is frequently increased. The Thrombopénie settles with the acute transformation.

Myélogramme

the osseous Moelle is very rich in cells, it shows a granulopoietic hyperplasy of fabric.

Other examinations: the rate of Uric acid of blood and the urinary excretion of uric acid are generally increased, in connection with the Hypermétabolisme of the nucleic acids of fabric in proliferation.

cytogenetic and molecular biology

Chromosomic chart

Chromosome Philadelphia T (9: 22)

P5% of the cases is Ph+, alone 5% are pH

FISH

insertion of Abl in Bcr

RT-PCR

Evolution and forecast

Chronic leukemia myéloïde (LMC) is fatal but in the long term. It inevitably changes have acute leukemia and at this time escapes very therapeutic.

Differential diagnoses

LMC can hardly be confused but with the reactions leucémoïdes which are not-leukaemic states in which the hematologic table and sometimes the clinical picture (weakens, large spleen, hemorrhages) present a certain resemblance to leukemias. The differential diagnosis can be possibly an essential Thrombocytémie. The chromosomic chart makes it possible to differentiate pathology completely.

Complications

Vascular: Thrombosis S and Hemorrhage S

The thrombocytose and the thrombopénie which accompanies any myéloprolifératif syndrome can be the cause of venous thromboses and hemorrhages (to think of the ulcer gastroduodénal). The thrombopathy which can be associated raises the hemorrhagic risk.

Vascular: Leucostase

The leucostase due to hyperleucocytosis can cause an acute respiratory insufficiency. At the bottom of eye, one can also observe a leukaemic retinite.

Metabolic: Hyperuricémie

The hyperuricemy, consequence of hyperleucocytosis, can appear by crises of drop or renal colics

Hématologique: Splénomégalie

The slénomégalie can become complicated of a hémodilution and a hypersplenism being accompanied by a thrombopénie and an anemia. When it is major, there can be splenic infarctions even a splenic risk of rupture.

Hematologic: medullary Insufficiency

The myélofibrose which accompanies the disease can be the cause of a medullary insufficiency. One finds a pancytopénie then (weakens, thrombopénie and neutropenia) appearing by an asthenia, hemorrhages and infections with pyogenes. The medullary insufficiency can also be due to a medullary invasion by immature cells, the blastes, during the accelerated or acute phase of the disease.

Hematologic: acute Leukemia

The transformation into secondary acute leukemia or acutisation is constant during the untreated evolution. In 70% of the cases, it is about an acute leukemia myéloïde, in 20% of a lymphoid acute leukemia and in 10% of a indifférentiée acute leukemia. The transformation appears by a deterioration of the general state, the appearance of a tumoral syndrome, a medullary insufficiency and by an increase in the blastes on the hémogramme. Very bad forecast, the evolution of this secondary acute leukemia is usually fatal in less than 6 months. The current treatments, grafts marrow, interféron, glivec transformed the forecast.

Treatments

Apart from very rare exceptions, leukemia myéloïde chronic incurable remainder. the median of survival is at 5 years and the exit is constantly fatal by transformation into acute leukemia. The treatment thus aims delaying to the maximum the acute transformation and at controlling hyperleucocytosis to prevent the complications. This is the forecast of the traditional drugs: Misulban and Hydréa. A cure is possible after allogreffe of osseous marrow either family (phratry) or nonfamily donor for the patients of less than 50 years. The Interféron alpha obtains remissions much longer. A revolution is in hand with the use of the Glivec (Imatinib) which transforms the forecast radically. This treatment recently put on the market indeed makes it possible to target the cancer cells: the chromosomal anomaly of the LMC causes a translocation between the chromosomes 9 and 22 (at the level of constrained the bcr and abl) which allows the formation of a protein which has an activity tyrosin aberrant kinase (exacerbated). Out, it is this activity which " give the ordre" with the cells to proliferate in an anarchistic way and prevents them from undergoing the apoptose (programmed cellular death). The Glivec has an inhibiting action of the activity tyrosin kinase of bcr-abl because it will be fixed on the site of connection of adenosine triphosphate of protein, preventing it functioning correctly and from giving its orders of cancerous proliferation. It is thus a treatment targeted to date which is now used in 1st intention .

The glivec is a very expensive drug (in the 2500 euros the box of thirty compressed of Glivec 400). So much of patients of the poor countries cannot have recourse there. This situation involves the protests of many humanitarian associations.

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