Acute lymphoblastoid leukosis

Description:

The acute lymphoblastoid leukosis is a group of heterogeneous malignant new growths of cells - the lymphoid predecessors (lymphoblasts) having certain genetic and immunophenotypic characteristics.

Acute lymphoblastoid leukoses the most widespread leukoses at children's and youthful age. The peak of incidence is the share of age from 1 year to 6 years. Spleens, a thymus, and also other bodies proceed with damage of marrow, lymph nodes.

Reasons of an acute lymphoblastoid leukosis:

Changes in structure of chromosomes, i.e. aberation chromosomes are the genetic cornerstone of development of an acute lymphoblastoid leukosis. At leukoses allocate specific or primary and nonspecific to an aberration hromomomnva. To primary it is accepted to carry translocations, deletions, inversions, amplifications of sites of the chromosomes containing oncogenes, genes of cellular receptors, genes of growth factors. Similar changes are capable to form the new sequences of DNA and emergence of new properties in a cell, formation of a specific clone. Secondary aberation chromosomes appear at a stage of a tumoral progression as a result of changes of the created clone. And similar aberrations can be observed at various options of leukoses. So, the Philadelphian chromosome can come to light both at acute, and at chronic leukoses.

The reasons of development of an acute lymphoblastoid leukosis in children still are definitely not established, however there are data on great value of infectious diseases at infantile age, to influence various physical (for example, radiodiagnosis, radiation therapy, the ionizing radiation), action of chemical mutagens. at benzene influence, among patients, poluyochavshy cytostatic immunodepressants (an imuran, Cyclophosphanum, лейкаран, sarcolysine, Mustargenum, etc.), biological (virus) mutagens on mother's organism during pregnancy. Also communication between many congenital chromosomal anomalies and development of an acute leukosis is proved.

Pathogeny:

In marrow, peripheral blood and in other bodies the tumor cells like lymphoblasts with CHIC-positive granules in cytoplasm which are not giving reactions to peroxidase, esterase and not containing lipids are found.

In 2/3 cases in tumor cells cytogenetic disturbances in the form of a polyploidy, the Philadelphian chromosome and a reciprocal translocation between chromosomes are found.

The cytogenesis of an acute lymphoblastoid leukosis is connected with predecessors of T-and B-lymphocytes. 10-15% of observations are the share of T-cellular leukoses in the countries of Europe. B-cellular leukoses prevail.

Being guided by immunological phenotypes of tumor cells, allocate several forms of a lymphoblastoid leukosis that matters for the choice of therapy and the forecast. The prevailing B-lymphoblastoid leukoses are presented early, intermediate and late by the options differing on an expression of CD10 paraglobulin, surface immunoglobulin and activity of a terminal dioksinukleotidtransferaza. Markers of a T-lymphoblastoid leukosis are CD7 antigens and T-receptors.

Symptoms of an acute lymphoblastoid leukosis:

Distinguish two types of a course of an acute lymphoblastoid leukosis: In-linear and T-linear, depending on type of cells - lymphoid predecessors.

All leukocytes in a human body are divided into 2 types - granulotsitarny and agranulocytic (granular and not granular), these two groups, in turn, are subdivided into eosinophils, basophiles, neutrophils (granulotsitarny), and lymphocytes (In - and T-type) and monocytes (agranulocytic). In the course of maturing and development (differentiation) all cells pass several stages, the blast stage (lymphoblasts) is first of which. Because of damage of marrow a tumor, lymphocytes do not manage to develop enough fully to execute the protective functions. Mostly, at an acute lymphoblastoid leukosis the V-lymphocytes (approximately in 85% of cases) which are responsible for antibody formation in an organism are surprised.
Clinical signs of an acute lymphoblastoid leukosis
Intoxication syndrome - weakness, fever, an indisposition, loss of weight. Fever can be connected also with existence bacterial, virus, fungal or protozoan (more rare) an infection, especially at children with a neutropenia (less than 1500 neutrophils in 1 мкл).
Hyperplastic syndrome - increase in all groups of peripheral lymph nodes. Infiltration of a liver and spleen leads to their increase that can be shown by abdominal pains. There can be pain and an ache in bones because of leukemic infiltration of a periosteum and the joint capsule and tumoral increase in volume of marrow. At the same time on roentgenograms it is possible to find changes, characteristic of leukemic infiltration, especially in tubular bones, near large joints.
Anemic syndrome - pallor, weakness, tachycardia, bleeding mucous oral cavities, a hemorrhagic syndrome on skin, pallor. Weakness results from anemia and intoxication.
The hemorrhagic syndrome is connected both with thrombocytopenia, and with intravascular thrombosis (especially at a hyperleukocytosis) and leads to emergence of petechias, ecchymomas on skin and mucous, to hemorrhages, a melena, vomiting with blood.
Initial increase in testicles (5-30% of cases of primary OLL) can be found in boys. These are painless, dense, one - or bilateral infiltrates. Especially often it happens at a hyperleukocytosis and T-cellular option of OLL.
The respiratory disturbances connected about increase in lymph nodes of a mediastinum which can result in respiratory insufficiency. This sign is characteristic of T-linear OLL.
There can be eye retinal apoplexies, hypostasis of an optic nerve. At an oftalmoskopiya leukemic plaques on an eyeground can be found.
Because of strongly reduced immunity any injury of skin is the infection center, there can be paronychias, felons infected stings of insects and traces of injections.

Damages of kidneys as a result of infiltration (clinical manifestations can be absent) and vypotny a pericardis because of disturbance of a lymph drainage between an endocardium and an epicardium can be rather rare complications.

Diagnosis:

For diagnosis of an acute lymphoblastoid leukosis the maintenance of blast cells in marrow has to be more than 30%. If the maintenance of blast cells in blood exceeds 30%, the diagnosis can be made also without marrow research.

Treatment of an acute lymphoblastoid leukosis:

There are several various ways of treatment of patients with adult OLL.

Some ways of treatment are standard (are applied now), and some new ways of treatment pass clinical test. Clinical testing is a research studying which purpose is improvement of a standard way of treatment or obtaining information on results of new ways of treatment of cancer patients. If clinical tests show that the new way of treatment is better, than the standard, new way of treatment can become a standard way of treatment afterwards. Patients can also take part in clinical tests. Only patients who did not undergo any treatment can take part in some clinical tests.

Treatment of an adult acute lymphoblastoid leukosis usually takes place in two stages.

Stages treatment of an adult acute lymphoblastoid leukosis:

Remissiono-induktsionnaya therapy. The purpose of this stage of treatment – to destroy leukemic cells in blood and marrow and to reach remission.

Postremissionny therapy. It is the second stage of treatment. Begins at once as soon as it is possible to reach remission. The purpose of postremissionny therapy – to destroy the remained leukemic cells which can be and not active, but afterwards can begin to grow and it will lead to a recurrence. This stage is called also continuation of remissionnny therapy.

Treatment-and-prophylactic therapy of the central nervous system is usually carried out at each stage of treatment. Because chemotherapeutic drugs are accepted orally or injections intravenously become, medicinal substance cannot often destroy the leukemic cells which got to TsNS – the central nervous system (a brain and a spinal cord). Leukemic cells find "shelter" (hide) in the central nervous system. The intrathecal chemotherapy and radiation therapy can destroy the leukemic cells which got to TsNS and by that to prevent a disease recurrence. Such type of treatment is called treatment-and-prophylactic therapy of TsNS.

Today there are four standard ways of treatment:

Chemotherapy.

Chemotherapy – a way of treatment of oncological diseases of strong chemotherapeutic drugs. Chemotherapeutic drugs are capable to stop and destroy growth of cancer cells, to prevent their department and penetration into other fabrics and bodies. At chemotherapy medicine can orally be taken (in the form of tablets, capsules) or intravenous or intramuscular injections are entered. Medicinal substance gets to a blood stream, spreads on an organism and strikes cancer cells (systematic chemotherapy). If the chemotherapeutic drugs are administered directly in a backbone (intrathecal chemotherapy), body or a cavity (for example, belly), medicinal substance strikes mainly cancer cells in these sites (regional chemotherapy). The combined chemotherapy – treatment at which more than one anticarcinogenic chemotherapeutic drug are used. The route of administration of chemotherapy depends on a look and a stage of an oncological disease.

The intrathecal chemotherapy can be applied at treatment of adult OLL which tends to distribution to a brain and a spinal cord. The therapy applied in order to avoid distribution of cancer cells in an organism and their penetrations into a brain or spinal cord is called treatment-and-prophylactic therapy of TsNS. The intrathecal chemotherapy is carried out in combination with usual chemotherapy at which medicines are accepted orally or in the form of injections.

Intrathecal chemotherapy. Antineoplastic means are entered into an intrathecal cavity of the vertebral channel where there is a cerebrospinal liquid (TsSZh is shown blue in the drawing). There are two different ways of administration of chemotherapeutic drugs. The first way, is represented in an upper part of the drawing, medicine to be administered in a tank of Ommaya. (A convex container which is entered into cerebral cavities. The container holds the main part of medicine that medicinal substance could come slowly to a brain through small tubules). Other method, is shown in the lower part of the drawing, medicine is administered directly in cerebrospinal liquid in a rachis at the level of a waist. The procedure to be carried out under a local anesthesia.

Radiation therapy.

Radiation therapy is a way of treatment of an oncological disease at which hard x-ray emission or other types of radiation radiations for destruction of cancer cells or prevention of growth of cancer cells are used. There are two types of radiation therapy. Radiation external therapy – the special device focuses radiation in the field of a tumor. Radiation internal therapy – use of the radioactive materials which are hermetically packed in needles, capsules, cores or catheters which are placed directly in or near a tumor. Radiation external therapy can be applied to treatment of adult OLL which tends to distribution to a brain and a spinal cord. It is called treatment-and-prophylactic therapy of TsNS.

Chemotherapy with the subsequent transplantation of stem cells.

Before transplantation of stem cells carry out chemotherapy. Transplantation of stem cells will be applied to substitution of abnormal krovoobrazuyushchy cells full. Stem cells (unripe blood cells) undertake from blood or marrow of the patient or the donor, frozen and remain. Upon completion of a chemotherapy course the kept stem cells defreeze and enter to the patient in the form of infusions of stem cells. The replaced stem cells get accustomed and help to recover the marrow cells producing blood cells.

Therapy by inhibitor kinase tyrosine.

The anticarcinogenic medicines called by inhibitors kinase tyrosine are used for treatment of some types of adult OLL. Drug blocks enzyme, tyrosine a kinase which promotes development from stem cells of a large number of leukocytes (granulocytes or blast cells). Today two such drugs Imatinib (Glivek) (imatinib mesylate) (Gleevec) and Dasatinib are used.

Some new ways of treatment pass clinical tests.

This section describes types of treatment which are at a stage of clinical tests. It is impossible to tell about all new ways of treatment which are studied. Information on clinical tests is available on NCI website

Biological therapy

Biological therapy is a way of treatment which involves immune system of the patient in fight against an oncological disease. Substances which are produced in an organism or which are synthesized in laboratory are used for stimulation or recovery of natural mechanisms of protection and fight against oncological diseases. Such type of treatment of an oncological disease is also called a biotherapy or an immunotherapy.

Patients can also take part in clinical tests.

For some patients participation in clinical tests is the best choice. Clinical tests are a part of research process. The purpose of carrying out clinical tests to establish: whether the new way of treatment is safe and effective or more the best, than a standard way of treatment.

Treatments, many of these standard ways, are based on results early the carried-out clinical tests. The patients who are taking part in clinical tests can receive standard treatment or take a course of a new way of treatment.

Patients who take part in clinical tests make a big contribution to researches and help to improve a way of cancer therapy in the future. Even, if results of clinical tests do not testify to efficiency of a new way of treatment, but they often give answers to very important issues and help to advance researches on a step forward.

Patients can participate in clinical tests before, in time and after they began to receive medical treatment.

Only patients who did not undergo any treatment can take part in some clinical tests. Patients at whom the disease will not respond to treatment can also participate in clinical tests. There are also clinical tests which investigate new ways of prevention of a recurrence or elimination of the side effects arising owing to cancer therapy.

Carrying out repeated inspection.

Some analyses which were made for diagnosis of cancer or a stage or a form of a disease can be made repeatedly. Sometimes analyses are carried out repeatedly to track efficiency of treatment. The decision on continuation, change or the termination of treatment is based on results of these analyses.

Some analyses need to be done from time to time and after the end of treatment. Results of analyses can show change of a condition of the patient or existence of a recurrence of a disease. Sometimes such analyses call control.