Myeloleukemia is a chronic neoplastic disease of the hematopoiesis system, which belongs to the leukemia group, which is characterized by a rather large amount of formation in the blood system of immature granulocytes. Myeloleukemia at the beginning of its development is an increased the number of leukocytes is almost up to 20,000 in μl, and in the unfolded phase of progression - up to 400,000 in μl. In the myelogram, as well as in the hemogram, there is a predominance of cells with different degrees of maturity, such as myelocytes, stab, promyelocytes and metamyelocytes.
With myeloleukemia, changes in the twenty-first and twenty-second chromosomes were identified, which distinguishes these cells from others. Very often this pathological disease is characterized by a significant increase in the blood of eosinophils and basophils, which indicates a more severe course of myeloid leukemia. With such an oncological disease, a characteristic symptom is splenomegaly, and for blood and bone marrow - myeloblasts in large numbers. The main methods of treatment are polychemotherapy and radiation exposure.
Myeloleukemia of the cause
The etiology of the development of myeloid leukemia remains unclear until now. But there are suggestions that in the emergence of both acute and chronic forms of myeloleukemia, a certain role of the disorder in the structure and composition of the chromosome apparatus plays a role, which are due to heredity or acquired under some influence of mutagenic factors.
To the causes of the development of myeloleukemia can be attributed to the effects of chemical carcinogens. There is evidence that acute myelogenous leukemia occurs among people who have been exposed to benzene or received cytotoxic drugs (Imuran, Mustargen, Sarkozolin, Leukeran, Cyclophosphamide). The frequency of this pathological disease among such patients increases several times. There are cases when myeloleukemia develops against the background of long-term treatment of other oncological diseases with the use of radiation exposure. Thus, ionizing radiation is considered one of the predisposing factors in the development of myeloid leukemia.
In addition, myeloid leukemia begins to develop due to non-innate chromosome damage in a single stem cell. What provokes her to such changes is not yet known. Perhaps, there are random exchanges at the genetic level between chromosomes, which are located very close to each other at a certain life stage of the cell. The applied analysis of chromosomes made it possible to find out that in myeloleukemia, clonal leukemic cells spread throughout the body - they are the descendants of one cell that was originally mutated. The unstable genotype of pathological cells in myeloleukemia promotes the appearance of clones in the original clone, and in addition, the selection of the most autonomous clones takes place under the influence of medical preparations. This phenomenon indicates the progression of myeloleukemia and its withdrawal from the control of cytostatic drugs.
Also, do not exclude the involvement of certain viruses in the occurrence of the disease.
Myeloid leukemia symptoms
This disease refers to chronic forms of leukemia. In myeloleukemia, the tumor process affects many bone marrow sprouts, such as red blood cells, platelets and granulocytes. The ancestor of the tumor is myelopoiesis, which is a precursor cell. The malignant process extends to the main hematopoietic organs, and in the final stage of the tumor any tissue can be affected.
The clinical picture of the disease is characterized by such stages of myeloid leukemia as the unfolded and terminal stages. At the first stages of the disease, the patient has no specific complaints of pathology, the spleen remains normal or may be slightly increased, and no changes in the composition of peripheral blood are noted.
Diagnosis of myeloid leukemia in the initial stage is carried out based on an analysis of elevated leukocytes with a shift to promyelocytes and myelocytes. In addition, there is a significant increase in the ratio between erythrocytes and leukocytes in the bone marrow, as well as the Philadelphia chromosome, which is localized in granulocytes. However, bone marrow trepanate from this period is characterized by absolute fat replacement by myeloid cells. Continuation of the developed stage can be observed for 4 years. With the appointment of the right treatment, the condition of patients with myeloid leukemia can remain satisfactory. They continue to work, to lead a habitual way of life for them, being on out-patient treatment and supervision.
The terminal stage of myeloid leukemia is manifested by all malignant traits. There is a fever with high temperature jumps, the patients begin to lose weight quickly, feel constant pain in the bones, feel weakness in the whole body. When palpation in these patients, splenomegaly and hepatomegaly are noted, sometimes lymph nodes increase. For this stage of myeloleukemia, certain changes in the composition of the blood are characteristic. This is characterized by the appearance and rapid growth of signs that suppress normal hematopoietic germs, such as granulocytopenia complicated by infection and necrosis on mucous membranes, thrombocytopenia with complications in the form of hemorrhagic syndrome and anemia.
The most important feature of the hematological character for the terminal stage of myeloid leukemia is an increased number of tumor cells (blasts). On the basis of karyological analysis, in the final stage, aneuploid clone cells are determined in almost 75% - these are hematopoietic cells that contain an irregular number of chromosomes.
Chronic myelogenous leukemia
This disease is considered a common type of leukemia, which accounts for almost 20% of all leukemia pathologies. Every year, myeloid leukemia in chronic form get sick in a ratio of 1.5: 100,000, evenly in all countries and stable for fifty years. In general, the disease affects people from 30 to 50 years with a large percentage of men. Children with this species of myeloid leukemia are sick quite rarely, about 2%.
The first reports of chronic myelogenous leukemia occur in 1845, when spleen increases were observed with a significant amount of neutrophils in the blood. And already Virkhov described in detail the histology of myeloid leukemia, where he linked changes in the composition of the blood and from the internal organs, giving him the name "spleen leukemia."
Today, when not only cytogenetic studies but also molecular studies are used in the diagnosis, there is no evidence of family chronic myelogenous leukemia. But ionizing radiation and some carcinogens play a peculiar role in the onset of the disease.
Chronic myelogenous leukemia occurs in such three stages as chronic, advanced (accelerating) and acute (terminal).
The chronic stage of myeloleukemia is characterized by a gradual increase in leukocytosis, an increase in platelets, granulocytes and spleen. In the beginning, myeloid leukemia has an asymptomatic period, which ends within a year to three years. In this period there is sweating, heaviness on the left under the rib and constant fatigue. Patients may seek advice from a specialist after the appearance of dyspnea and severity in the epigastric region after eating, which forces them to limit the use of a one-time amount of food. In this case, an X-ray examination reveals a highly elevated dome of the diaphragm, a compressed and pushed out lung, and a squashed stomach with huge spleen sizes. When palpating, it is very dense, but painless. But with a fairly significant increase in this body develops a spleen infarction, which is a signal to call for qualified specialists.
Clinically, the spleen infarct is characterized as acute pain on the left under the ribs, which radiate in the back, with temperature rises up to 38 ° C with symptoms of intoxication. At this point, the spleen is very painful, the noise is heard in the form of friction over the infarction zone, which is due to perisplenitis.
In 35% of patients, hepatomegaly is observed with a pronounced form of splenomegaly. In some cases, hyperleukocytosis causes painful priapism, and in rare cases - visual impairment and inhibition with pain in the head.
The increased viscosity of the blood can cause the development of veno-inclusive lesions of the liver. In this stage of myeloid leukemia, using a cytogenetic study, only the Ph-chromosome (9 and 22) are detected, for which additional changes are not characteristic.
The stage of acceleration proceeds without certain symptoms or they may not be particularly pronounced. As a rule, the patient is in a satisfactory condition, but sometimes there may be unnatural temperature rises, fatigue appears sooner after some work is done, a spleen is felt that previously could not be palpated.
The main picture of the transition of myeloleukemia from the chronic stage to acceleration is the change in blood composition. There is an increase in leukocytes, which managed to control the treatment before, myelocytes, metamyelocytes increase, and also promyelocytes and blast cells in the amount of up to 2%. Also up to 30% increase in basophils. Therefore, patients with such a large number of basophils complain about the itching of the skin , the appearance of a fever with periodic leakage and loose stools, which is due to a significant amount of histamine in the blood that is produced by basophils.
If, after increasing the dose of the chemotherapeutic drug, the percentage of basophils does not decrease, this indicates a poor prognosis and the imminent occurrence of the terminal stage of myeloid leukemia. For a later period of acceleration, pain in bony bones or joints, a tendency to infectious diseases and weight loss are characteristic.
The stage of acceleration can be determined in almost 70% of patients. And its sudden transition to the terminal stage is observed in patients with a long first stage of more than eight years (chronic).
The terminal stage of chronic myelogenous leukemia begins with the appearance of severe weakness, prolonged aching, and sometimes very severe joint pain and pain in bones with periodic fever up to 39 ° C, often accompanied by chills, pouring sweat and weight loss.
Very often, a rapid splenomegaly is diagnosed with a spleen infarction that develops in the future. In addition, there is an increase in the liver before protrusion from under the edge of the rib by 35 cm. Symptoms of hemorrhagic syndrome also appear. Patients in this stage are in very serious condition. Most patients develop blast crisis, characteristic for blood cells and bone marrow. Almost 50% of the patients are diagnosed with bone marrow fibrosis. Many at this time note normochromic anemia and thrombocytopenia of different depths. At 5-10% there are local extramedullary blast infiltrates, which contribute to the development of myeloblastoma. Often peripheral lymph nodes or mediastinal lesions are affected. In general, one lymph node becomes painful and painful, but then other lymph nodes, as well as organs, join it.
Very rarely there is a CNS lesion with neiroleukemia or nerve infiltration in the peripheral system with the development of pain and paresis.
Myeloleukemia in children is more common in the juvenile version of the disease. In this case there is a low hemoglobin, a decrease in platelets and erythrocytes, an increase in monocytes with the presence of blast cells and the absence of basophils and eosinophils. The bone marrow is characterized by an increased content of monocytes and blasts. Characterized by lymphadenopathy with splenomegaly and hepatomegaly. Today this variant is considered as chronic myelomonocytic leukemia in children.
Acute myelogenous leukemia
This disease refers to the malignant pathology of myeloid cells, as a result of which they undergo a rapid process of reproduction and replacement, while inhibiting the growth of healthy blood cells. The symptomatology of acute myelogenous leukemia consists of the processes of replacement of bone marrow cells with leukemia, and this causes the decrease in normal leukocytes, erythrocytes and platelets.
Myeloleukemia of an acute form is characterized by the appearance of signs of fatigue, dyspnea, small skin lesions with increased bleeding and infectious complications.
To date, the causes of this disease are not known to the end. But some factors that contribute to the development of acute myelogenous leukemia have been identified. These include ionizing radiation, exposure to harmful substances and mutation at the genetic level.
Many symptoms in the acute form of myeloid leukemia are caused by the replacement of normal hematopoietic cells by tumor. Insufficient number of leukocytes leads to a decrease in immune defense and increases the susceptibility of patients to infections. Reduction of red blood cells causes anemia, which is expressed in fatigue, pale skin and difficulty breathing. Reduced platelet counts result in mild skin damage and increased bleeding.
At the very beginning of the disease, acute myelogenous leukemia can occur as signs of an influenza state with fever, fatigue, weight loss or a decrease in appetite, dyspnea, anemia, the appearance of bruising, joint and bone pain, and the attachment of infections.
With acute myelogenous leukemia, minor and asymptomatic splenomegaly is observed. There is also a frequent increase in lymph nodes. Sometimes, with this form of myeloid leukemia, there are changes in the skin and Sweet syndrome.
In addition, patients are diagnosed with swelling in the gum area as a result of the infiltration process of leukemic cells in the tissue. In some cases, the first sign of the disease is detected as a dense tumor mass outside the bone marrow.
In rare cases, acute myeloid leukemia is detected during a preventive examination due to a general analysis of blood against the background of asymptomatic illness.
As a rule, myeloleukemia in acute form develops very rapidly and without appropriate treatment can turn into a lethal outcome for a few months and even weeks.
The prognosis for acute myelogenous leukemia with a five-year survival rate can vary from 15 to 70%, and remission - up to 78%. And it will depend on the subspecies of malignant disease.
When choosing the main treatment for myeloid leukemia, the stages of the disease are put in the basis. For the chronic stage, when clinical and hematological manifestations are poorly expressed, general restorative therapy is prescribed, a full-fledged vitaminized diet with regular dispensary supervision. Interferon is used, which favorably influences the course of malignant pathology.
The main method of therapeutic treatment of myeloleukemia is the use of cytotoxic drugs that block the growth of all cells, especially tumor cells. But these medicines cause the development of side effects manifested by inflammation of the mucosa of the gastrointestinal tract, hair loss, nausea, etc. In addition, radiation exposure, transfusion of blood substitutes and stem cell transplantation are used.
The use of self-therapy for the treatment of myeloid leukemia is unacceptable. As a rule, the disease begins to be treated during the progression of the pathological process. Effective is the chemotherapeutic drug Myelosan (6-8 mg per day) with leukocytes more than one hundred thousand in 1 μl with the simultaneous use of alkaline drink in significant quantities. And also appoint Allopurin at 0.3 twice a day. As soon as the blood counts are normalized and the number of leukocytes decreases, Myelosan is used at 2 mg per day or every other day, and then maintenance therapy is used - once a week for 4 mg. Be sure to pass the control of the blood composition once every two weeks, and then switch to once a month.
Patients with myeloid leukemia may also benefit from outpatient treatment. If there is resistance to Myelosan, and there is also a thrombocythemic syndrome, then 250 mg of myelobromol is administered every day or Hydroxyurea up to 6 g daily. In the amount of three to nine million units, therapeutic courses with the use of Interferon, subcutaneously or intramuscularly for a year or much longer, are effective. by indications. And the rest of the drugs can not be used.
Absolute cure can be achieved after stem cell transplantation, but this requires HLA-compatibility of these cells in the donor with the patient.
Also, with a strong increase in the spleen, radiation therapy is used at a dose of three to seven Gy.
To cure the terminal stage of myeloid leukemia, Cytosar, Vincristine, Rubomycin, Prednisolone, Intron A, and GRP regimen are prescribed.
Blastic crisis treatment is performed by protocols of acute myeloid leukemia or lymphoblastic leukemia therapy, which will depend on the phenotype of these malignant blasts.
Cytostatic drug at any stage of myeloleukemia is Hydroxyurea at an initial dose of 20 to 30 mg / kg once a day with a weekly blood test.
There is also evidence that the use of Imatinib improves clinical and hematological indicators and leads to cytogenetic remissions. In addition, the Philadelphia chromosome disappears.
Thus, early diagnosis of myeloleukemia and timely treatment at the initial stage, increase the favorable prognosis of the disease, in contrast to the acceleration phase or blast crisis.