Myelosis

Description:

Chronic miyeloblastny leukosis (HML, myelosis, chronic myeloid leukosis) — a leukosis form which is characterized by the strengthened and non-regulated growth of preferential myeloid cells in marrow with their accumulation in blood. HML — a hemopoietic clonal disease which main display is proliferation of mature granulocytes (neutrophils, eosinophils and basophiles) and their predecessors; the option of a myeloproliferative disease associated with a characteristic chromosomal translocation (the Philadelphian chromosome). Now the main way of treatment of a myelosis is targetny (target) therapy imatiniby and other drugs, considerably improved survival indicators.

Myelosis symptoms:

The disease often proceeds asymptomatically, coming to light at routine clinical blood test. In this case HML should differentiate from a leukemoid test at which the blood smear can has a similar picture. HML can be shown by an indisposition, subfebrile fever, the gout raised by a susceptibility to infections, anemia, thrombocytopenia with bleeding (though the increased maintenance of thrombocytes can be also observed). Also the splenomegaly is noted.
HML often divide into three phases on the basis of clinical characteristics and datas of laboratory. For lack of treatment, HML usually begins with a chronic phase, within several years progresses in a phase of acceleration and, eventually, blast crisis develops. Blast crisis — terminal phase HML, clinically similar to an acute leukosis. One of progression factors from a chronic phase to blast crisis is acquisition of new chromosomal anomalies (in addition to the Philadelphian chromosome). Some patients by the time of diagnosis can be already in a phase of acceleration or in blast crisis.
About 85% of patients with HML by the time of diagnosis are in a chronic phase. During this phase clinical manifestations usually are absent or there are "easy" symptoms, such as an indisposition or feeling of overflow of a stomach. Duration of a chronic phase is various and depends on that how the disease, and also from the carried-out treatment was early diagnosed. Eventually, in the absence of effective treatment, the disease passes into an acceleration phase.

Acceleration phase.
Diagnostic criteria of transition to a phase of acceleration can differ: the criteria established by researchers of the oncological center of Anderson at the Texas university, Sokaly with coauthors and also are most widely used by World Health Organization. Criteria of WHO are probably most eurysynusic, and distinguish an acceleration phase the following:

    * 10-19% of myeloblasts in blood or marrow
    *> 20% of basophiles in blood or marrow
    *<100,000 тромбоцитов, вне связи с терапией
    *> 1,000,000, regardless of therapy
    * Cytogenetic evolution with development of new anomalies in addition to the Philadelphian chromosome
    * Progressing of a splenomegaly or increase in number of leukocytes, regardless of therapy.

The phase of acceleration is supposed in the presence of any of the specified criteria. The phase of acceleration indicates a progression of a disease and the expected blast crisis

Blast crisis.
Blast crisis — the final stage of development of HML proceeding like an acute leukosis with a bystry progression and short survival. Blast crisis is diagnosed on the basis of one of the following signs for the patient with HML:

    *> 20% of myeloblasts or lymphoblasts in blood or marrow
    * Large groups of blasts in marrow at a biopsy
    * Development of a hloroma (solid focus of leukemia out of marrow)

Myelosis reasons:

HML became the first malignant disease with the revealed genetic anomaly, a chromosomal translocation which is shown by a pathological Philadelphian chromosome. This chromosomal pathology received the name as it was for the first time open and described in 1960 by scientists from Philadelphia, Pennsylvania, the USA: Peter Nouyell (Pennsylvanian university) and David Hangerford (university Templ).

At this translocation, a part from the 9th and 22nd chromosomes are interchanged the position. As a result, the ABL gene from a chromosome 9 is attached to a part of a BCR gene from a chromosome 22. This abnormal "merged" gene generates protein of p210, or, sometimes, p185. As abl has the area adding phosphatic group to the tirozinovy rest (tyrosine kinase), the product of an abnormal gene is also tyrosine kinase.

Protein of BCR-ABL interacts with a part of a cellular receptor to SILT-3 (CD123 antigen). The transcription of BCR-ABL works continuously and does not need activation by other proteins. On the other hand, BCR-ABL activates the proteinaceous cascade controlling a cellular cycle, accelerating cell fission. Moreover, protein of BCR-ABL suppresses DNA repair, causing instability of a genome and doing a cell more susceptible to further genetic anomalies. Activity of BCR-ABL — the pathophysiological reason of a myelosis. With improvement of understanding of the nature of BCR-ABL of protein and its action in quality tyrosine kinase, the targetny (target) therapy allowing to inhibit specifically activity of BCR-ABL of protein was developed. These inhibitors tyrosine kinase can promote full remission of HML that once again confirms the leading role of bcr-abl in development of a disease.

Treatment of the Myelosis:

Treatment at a myelosis is begun after establishment of the diagnosis and usually out on an outpatient basis.

In the absence of myelosis symptoms against the background of the stable leukocytosis which is not exceeding 40-50 - 109/l apply hydroxurea or бусульфан before achievement of maintenance of leukocytes in blood 20*109/l.

In process of progressing of a myelosis are shown hydroxurea (a gidrea, литалир), a-IFN. At a considerable splenomegaly carry out radiation of a spleen.

At the expressed symptomatology of a myelosis use combinations of the drugs used at acute leukoses: Vincristinum and Prednisolonum, Cytarabinum (Cytosarum) and даунорубицин (rubomitsina hydrochloride). At the beginning of an end-stage Mitobronitolum is sometimes effective (миелобромол).

Now for therapy of a myelosis new drug — a blocker of a mutant tyrosinekinase (r210) — Gliveka (STI-571) is offered. At blast crisis of HML and at Ph-positive OLL the dose is increased. Use of drug leads to full remission of a disease without eradikation of a tumoral clone.

The transplantation of stem cells of blood or red marrow which is carried out by the patient is younger than 50 years in the I stage of a disease, in 70% of cases leads to recovery.