Lymphoblastic blood leukemia is considered the most common oncological pathology of children. It accounts for approximately 25% of the total number of cancerous tumors detected in pediatrics. Further we will consider more in detail a leukemia of a blood - what is it, why he appears and what therapeutic actions are spent at this pathology.
Blood leukemia - what is it? This disease belongs to the group of cancer. ALL (acute lymphoblastic leukemia), the symptoms of which will be discussed below, is a group of heterogeneous neoplasms from cells that have certain immunophenotypic and genetic characteristics. Increase in production and accumulation of these elements in the bone marrow is facilitated by secondary anomalies of proliferation, differentiation of either one. As a result, the cells infiltrate the parenchymal organs and lymph nodes. Most (about 80%) of all leukemia (leukemia) detected in children is lymphoid in nature.
Malignant blood diseases today are found everywhere in the world. The prevalence of ALL in developed countries is 3-4 cases per hundred thousand children per year. In Central Asia and Africa, pathology is less common. Oll is often celebrated in the USA, Japan, China, Europe. The peak of the incidence in children is considered to be 2.5-5 years old. More often the pathology develops in boys.
First of all, they include the age of the mother during the antenatal period, the large weight of the newborn - more than 4000 g, post- and prenatal exposure to ionizing radiation. In what cases can acute lymphoblastic leukemia occur? The history of the mother's illness may contain information about the death of the fetus in a previous pregnancy. This could be due to adverse environmental conditions or due to a genetic predisposition. If there are oncologically sick relatives in the family, the likelihood of an acute lymphoblastic leukemia in the future generations increases. Causes of the disease can be associated with syndromes of chromosome element instability. These include, in particular, Down syndrome, neurofibromatosis, variable immunodeficiency, Fanconi anemia, X-linked agammaglobulinemia (congenital), and others. As a result of several studies, specialists came to the conclusion that in acute lymphoblastic leukemia, as in the development of other oncologies, a spontaneous mutation of progenitor cells occurs. It is subsequently complicated by environmental triggering factors that activate proliferation. These are the most common phenomena that can provoke leukemia. The causes of the appearance of pathology are one of the fundamental moments in the choice of therapeutic methods.
If any pathology of oncology is identified, the clinical characteristics and signs of the cells that make up the tumor substrate are taken into account. The diagnosis of ALL is made on the basis of paraclinical and physical examinations, data of anamnesis and laboratory studies.
The signs of leukemia are a complex of several syndromes:
- Intoxicating. With acute lymphoblastic leukemia, malaise, weight loss, weakness, fever are noted. The latter can be provoked by a viral, bacterial, protozoal (rare) or fungal infection, especially in patients with neutropenia.
- Hyperplastic. In acute lymphoblastic leukemia, the spleen and liver infiltrate. This, in turn, leads to hepatosplenomegaly, which can be manifested by soreness in the abdomen. The first signs of leukemia are pathological fractures of tubular bones or the spine. Soreness and puffiness of the joints can initially be taken for manifestations of rheumatoid arthritis or other disorders. Lesions of bones - for osteomyelitis. With leukemia infiltration of the joint capsule and periosteum, infarction and tumor enlargement of the bone marrow, extensive pains appear in the volume. Together with this, the roentgenogram reveals the changes characteristic of the pathological state. Especially clearly they are visible near large joints and in tubular bones. Soreness can occur later, due to aseptic necrosis and osteoporosis.
- Anemic. In acute lymphoblastic leukemia, there is tachycardia, pallor, mucous bleeding in the mouth, hemorrhagic syndrome on the skin. As a result of intoxication and anemia, weakness develops.
Manifestation of pathology
In 5-30% of cases of primary acute lymphoblastic leukemia in boys, an initial increase in testes is observed. There are two- or one-sided, dense, painless infiltrates. In practice, cases of significant renal enlargement have been reported. In this case, there may be no clinical manifestations of their defeat. To rare complications include effeminate pericarditis and infiltration of the myocardium against the background of obstruction of the lymphatic drain between the epicardium and the endocardium. With an increase in lymph nodes in the mediastinum, disturbances in the activity of the respiratory system may occur. These signs of leukemia of the T-cell type lead to the development of the syndrome of the hollow superior vein. Respiratory failure may also occur. In a number of cases, leukemic infiltration of pulmonary tissues or hemorrhage in them is noted. Sometimes it is difficult for specialists to differentiate these complications from infectious pathologies. Among the common signs of eye damage against the background of acute lymphoblastic leukemia, hemorrhage into the retina, edema of the nipple in the optic nerve, and infiltration of the vessels should be noted. With ophthalmoscopy, plaques can be detected at the bottom of the eyeball. Probably also the presence of dense cyanotic infiltrative painless elements on the skin. With any damage to the cover, an infection can develop. In this regard, during the diagnosis can be identified panaritium, paronychia, infected bites of various insects, traces of injections, etc.
Paraclinical studies: UAC
Hemoglobin can be lowered or normal. Hematocrit and the number of erythrocytes are usually reduced. There is a decrease in the number of reticulocytes. The number of leukocytes can be reduced, elevated or normal. However, in this case, not all cases can be detected power cells. For pathology, a "leukemia failure" is characteristic. It is about the presence of power cells against the background of the absence of intermediate forms - metamyelocytes and myelocytes - in the blood formula. Thrombocytopenia is common.
This procedure is the taking of a bone marrow puncture. The material must be taken from a minimum of two points. The procedure is preferably under general anesthesia. In children older than two years, puncture is taken from the anterior and posterior crests of the iliac bones, up to 2 years - from the calcaneal segments or tuberosity of the tibial elements. In the cytological morphological study, as a rule, hypercellular medullar material with narrowed sprouts of the normal hematopoiesis system and infiltration of blast cell structures is detected.
This is one of the mandatory stages of diagnosis. With the use of cytochemical staining, it is revealed to which line the cells belong. It is mandatory to use myeloperoxidase.
This is also a mandatory diagnostic procedure for suspected acute lymphoblastic leukemia, the causes of which are indicated above. Spinal puncture should be performed in sedation and in the presence of at least 30 thousand / μl of platelets in the peripheral blood. If necessary, transfusion of thrombin suspension is performed before the procedure. In order to prepare a cytopreparation, it will take at least two milliliters of liquor. When detecting power elements and signs of damage in the cranial nerves, a diagnosis is made of neuroleukemia-leukemia CNS damage. It should be noted, however, that the penetration of the lymphoblasts into the nervous system and the infiltration of the brain envelopes occur in all cases, even in the absence of clinical and laboratory manifestations. It is also desirable, and if neurological symptoms are detected, it is necessary to conduct a computer or magnetic-nuclear tomography of the spinal cord or brain.
With the help of ultrasound of the retroperitoneal space and the abdominal cavity, the size of the parenchymal infiltrated organs, enlarged lymph nodes in the abdominal cavity and other areas, organs in the small pelvis, and testicles can be clarified. As part of the diagnosis, a chest X-ray is performed in two projections. This is necessary to detect an increase in the mediastinum. If there are indications, x-rays of the joints and bones are assigned. Within the framework of laboratory studies, biochemical analysis is carried out. It usually shows an increase in LDH of more than 500 IU, a possible disruption in the activity of the liver and kidneys. Before the start of chemotherapy, EchoCG and ECG are recommended. Today, among other methods, molecular-genetic and cytogenetic methods for determining the number of chromosomes, as well as their structural changes, are used in the study of affected cells.
Therapy: general information
The basic principle on which modern pediatric oncohematology is built is the division of patients into groups according to the intensity of therapy. It is selected depending on the severity with which acute lymphoblastic leukemia occurs. The prognosis of the state is also of great importance. So, for example, those who are not recommended to receive more toxic and heavy means for eliminating the pathology of moderate enough chemotherapy are categorically not recommended. At the same time, for those whose expected survival is not so high, intensification of interventions can become a chance for recovery. When divided into groups of patients who have leukemia diagnosed, the prognosis is made on the basis of previous experience, as well as individual protocols entered in classification systems. In each of them, one or another strategy of therapeutic measures of a certain intensity is formed. With the existing classification, a general agreement was adopted on the distribution of the risk groups of patients who are diagnosed with acute lymphoblastic leukemia. The treatment of children was developed in the late sixties of the last century in America. By and large, the principles on which the therapeutic tactics are built have not undergone any particular changes. In patients under the age of one year, the pathology manifests itself in an extremely aggressive form and is characterized by neuroleukemia, leukocytosis.
Basic therapeutic methods
In the treatment used drugs such as "Prednisolone" and "Vincristine." Endoluminal administration of the drug "Methotrexate" and cranial irradiation for the prevention of neuroleukemia are also used. A special treatment program was also developed. This means that all patients received clearly defined dosages and combinations of chemotherapy drugs within a specific time frame, according to the protocol. By the end of the seventies it became clear that after passing such a program, about 50% of children recovered from whom leukemia was diagnosed. The reasons for further progress in the therapy of pathology are due to the determination of the heterogeneity of ALL and the subsequent introduction of international cytological classification systems and prognostic factors, the distribution of patients into groups, the development of differentiated programs. Of great importance was the organization of multicenter studies, the study of the pharmacokinetics of various cytotoxic agents for the formation of more effective chemotherapeutic regimens, and the intensive development of accompanying measures.
Basic principles of therapy
Thanks to the measures described above, new generation chemotherapy programs were created. Most protocols used today are based on the principles of initial intensive therapy, whose goal is to maximize the destruction of the pathological cell pool. The basis for the development of therapeutic programs is the use of cytostatics in the form of combinations that replace each other (rotation), high-dose chemotherapy regimens, as well as intensive prevention of pathology.
Features of the use of drugs
The main therapeutic and preventive measures for neiroleukemia are intrathecal administration of the drugs "Prednisolone", "Cytosar", "Methotrexate" (in dosages according to age) and cranial irradiation. The latter is carried out at the initial stages of therapy. With endolumbular injection, the drug "Methotrexate" has a systemic effect. In this regard, to reduce the tumor mass, early first lumbar treatment puncture is necessary. Cranial irradiation has distant and immediate side effects. In this regard, studies to optimize ALL therapy, conducted today, are aimed at reducing the dose and clear allocation of patients from the low-risk group, for whom this radiation therapy is not mandatory. All these achievements allowed the end of the eighties ready for the last century to overcome the 70% barrier of five-year survival in leukemia in children without relapses.
Modern therapeutic programs
The treatment that is used today includes several phases. The first is induction of remission using three or more agents that are administered for 4-6 weeks. The second is multi-agent consolidation of the previous phase. The third is maintenance therapy. As a rule, in the last phase, antimetabolites are used for 2-3 years. Accompanying therapy helps prevent and eliminate many complications associated with induced cytopenia and immunosuppression. The need to use supportive therapy for 2-3 years was proved in the middle of the last century. Usually during this period every day the patient takes the drug "6-markaptopurian". Every week he is given the drug "Methotrexate". Depending on the number of leukocytes, a dosage is established. As practice shows, patients have a satisfactory tolerability of such a therapeutic regimen. Implementing supportive activities at 80% of the required volume is considered an unfavorable prognostic factor in terms of relapse.
There are a number of problems in the treatment of ALL. In particular, the number of patients with mutant tumor cell clones that are resistant to chemotherapy, the high cost and the appearance of late side effects (neuroendocrine disorders, growth disorders, secondary tumors) is increasing. Failures in induction treatment are due to early death of patients due to toxic complications or a resistant tumor. Also, approaches to the therapy of patients who did not respond to the standard regimen are very limited. As an alternative, such agents as "Teniposide", "Vepesid", "Cytosar" are used. Today, about 70% of children have a 5-year remission. Acute lymphoblastic leukemia in adults recurs in every seventh case. This suggests that the duration of the remission period can be achieved only in 20% of cases. As a rule, the return of pathology is noted in the first 2 years after diagnosis. The state of remission is characterized as the lack of power cells in the blood, the presence of less than 5% of blasts in bone marrow tissue, the appearance of signs of restoration of the norm of hematopoiesis. In the analysis of cerebrospinal fluid, less than 5 mononuclears / microliters are detected. For the success of treatment, it is necessary to quickly achieve a state of remission. In 90% of patients, as a rule, pathological cells show sensitivity to chemotherapy.
The main goal of therapy is to save the patient from pathology and return him to normal social life and to a good health condition with a minimum of complications due to treatment. To achieve this today is quite difficult. This is due to the fact that most antileukemic drugs are not selective and toxic. However, the achievements in the field of understanding the clinical and biological heterogeneity of pathology, the constant conduct of various studies give hope that the molecular pathogenesis of the disease will nevertheless be deciphered to the end. In this case, knowledge about the mechanisms of tumor transformation will allow to develop more effective and least toxic therapeutic agents.