Acute lymphoblastic leukemia is a malignant lesion of the hematopoiesis system, accompanied by an uncontrolled increase in the number of lymphoblasts. It is manifested by anemia, symptoms of intoxication, enlarged lymph nodes, liver and spleen, increased bleeding and respiratory disorders. Due to a decrease in immunity in acute lymphoblastic leukemia, infectious diseases often develop. CNS damage is possible. The diagnosis is made on the basis of clinical symptoms and laboratory data. Treatment – chemotherapy, radiotherapy, bone marrow transplantation.
C91.0 Acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. The share of ALL is 75-80% of the total number of cases of diseases of the hematopoiesis system in children. The peak incidence occurs at the age of 1-6 years. Boys suffer more often than girls. Adult patients get sick 8-10 times less often than children. In children, acute lymphoblastic leukemia occurs primarily, in adults it is often a complication of chronic lymphocytic leukemia. In its clinical manifestations, ALL is similar to other acute leukemias. A distinctive feature is a more frequent lesion of the membranes of the brain and spinal cord (neuroleukosis), which develops in 30-50% of patients in the absence of prevention. The treatment is carried out by specialists in the field of oncology and hematology.
According to the WHO classification, there are four types of ALL: pre-pre-B-cell, pre-B-cell, B-cell and T-cell. B-cell acute lymphoblastic leukemias account for 80-85% of the total number of cases of the disease. The first peak of morbidity occurs at the age of 3 years. Subsequently, the probability of developing ALL increases after 60 years. T-cell leukemia accounts for 15-20% of the total number of cases of the disease. The peak incidence occurs at the age of 15 years.
The immediate cause of acute lymphoblastic leukemia is the formation of a malignant clone – a group of cells with the ability to multiply uncontrollably. A clone is formed as a result of chromosomal aberrations: translocation (exchange of sections between two chromosomes), deletion (loss of a section of a chromosome), inversion (reversal of a section of a chromosome) or amplification (formation of additional copies of a section of a chromosome). It is assumed that genetic disorders that cause the development of acute lymphoblastic leukemia occur even in the prenatal period, however, additional external circumstances are often required to complete the process of forming a malignant clone.
Among the risk factors for acute lymphoblastic leukemia, radiation exposure is usually primarily indicated: living in an area with an increased level of ionizing radiation, radiotherapy in the treatment of other oncological diseases, numerous X-ray examinations, including in the prenatal period. The level of communication, as well as the evidence of the dependence between various radiation exposures and the development of acute lymphoblastic leukemia, vary greatly.
So, the relationship between leukemia and radiation therapy is now considered proven. The risk of acute lymphoblastic leukemia after radiotherapy is 10%. In 85% of patients, the disease is diagnosed within 10 years after the end of the course of radiation therapy. The relationship between X-ray studies and the development of acute lymphoblastic leukemia currently remains at the level of assumptions. Reliable statistical data confirming this theory does not yet exist.
Many researchers point to a possible link between ALL and infectious diseases. The virus of the causative agent of acute lymphoblastic leukemia has not yet been identified. There are two main hypotheses. The first is that ALL is caused by one virus that has not yet been identified, but the disease occurs only if there is a predisposition. The second is that different viruses can cause the development of acute lymphoblastic leukemia, the risk of developing leukemia in children increases with a lack of contact with pathogenic microorganisms at an early age (with an “untrained” immune system). So far, both hypotheses have not been proven. Reliable information about the presence of a link between leukemia and viral diseases was obtained only for T-cell leukemia in adult patients living in Asian countries.
The probability of developing acute lymphoblastic leukemia increases with the mother’s contact with certain toxic substances during gestation, with certain genetic abnormalities (Fanconi anemia, Down syndrome, Schwachman syndrome, Klinefelter syndrome, Wiskott-Aldrich syndrome, neurofibromatosis, celiac disease, hereditary immune disorders), the presence of oncological diseases in the family history and taking cytostatics. Some experts note the possible negative impact of smoking.
The disease develops rapidly. By the time of diagnosis, the total mass of lymphoblasts in the body may be 3-4% of the total body weight, which is due to the rapid proliferation of malignant clone cells over the previous 1-3 months. Within a week, the number of cells increases by about half. There are several syndromes characteristic of acute lymphoblastic leukemia: intoxication, hyperplastic, anemic, hemorrhagic, infectious.
Intoxication syndrome includes weakness, fatigue, fever and weight loss. An increase in temperature can be provoked by both the underlying disease and infectious complications, which are especially common in the presence of neutropenia. Hyperplastic syndrome in acute lymphoblastic leukemia is manifested by an increase in lymph nodes, liver and spleen (as a result of leukemic infiltration of the parenchyma of organs). With an increase in parenchymal organs, abdominal pain may appear. An increase in the volume of bone marrow, infiltration of the periosteum and tissues of joint capsules can cause aching bone and joint pain.
The presence of anemic syndrome is indicated by weakness, dizziness, pallor of the skin and increased heart rate. The cause of hemorrhagic syndrome in acute lymphoblastic leukemia is thrombocytopenia and thrombosis of small vessels. Petechiae and ecchymoses are detected on the skin and mucous membranes. With bruises, extensive subcutaneous hemorrhages easily occur. There is increased bleeding from wounds and scratches, retinal hemorrhages, gingival and nasal bleeding. Some patients with acute lymphoblastic leukemia have gastrointestinal bleeding, accompanied by bloody vomiting and tar-like stools.
Immune disorders in acute lymphoblastic leukemia are manifested by frequent infection of wounds, scratches and puncture marks. Various bacterial, viral and fungal infections can develop. With an increase in the lymph nodes of the mediastinum, respiratory disorders are noted due to a decrease in lung volume. Respiratory failure is more often found in T-cell acute lymphoblastic leukemia. Neuroleukosis, provoked by infiltration of the membranes of the spinal cord and brain, is more often noted during relapses.
With the involvement of the central nervous system, positive meningeal symptoms and signs of increased intracranial pressure (edema of the optic nerve discs, headache, nausea and vomiting) are revealed. Sometimes the defeat of the central nervous system in acute lymphoblastic leukemia is asymptomatic and is diagnosed only after examination of the cerebrospinal fluid. 5-30% of boys have infiltrates in the testicles. In patients of both sexes, purplish-cyanotic infiltrates (leukemides) may occur on the skin and mucous membranes. In rare cases, effusion pericarditis and impaired renal function are observed. Cases of intestinal lesions are described.
Taking into account the peculiarities of clinical symptoms, four periods of development of acute lymphoblastic leukemia can be distinguished: initial, peak, remission, terminal. The duration of the initial period is 1-3 months. Nonspecific symptoms prevail: lethargy, fatigue, decreased appetite, subfebrility and increasing pallor of the skin. Headaches, abdominal pain, bones and joints are possible. During the height of acute lymphoblastic leukemia, all the characteristic syndromes listed above are revealed. During the period of remission, the manifestations of the disease disappear. The terminal period is characterized by a progressive deterioration of the patient’s condition and ends with a fatal outcome.
The diagnosis is made taking into account clinical signs, the results of peripheral blood analysis and myelogram data. Anemia, thrombocytopenia, increased ESR and changes in the number of leukocytes (usually leukocytosis) are detected in the peripheral blood of patients with acute lymphoblastic leukemia. Lymphoblasts make up 15-20 percent or more of the total number of white blood cells. The number of neutrophils is reduced. Blast cells predominate in the myelogram, pronounced inhibition of erythroid, neutrophil and platelet growth is determined.
The examination program for acute lymphoblastic leukemia includes lumbar puncture (to exclude neuroleukosis), ultrasound of the abdominal cavity (to assess the condition of parenchymal organs and lymph nodes), chest X-ray (to detect enlarged mediastinal lymph nodes) and biochemical blood analysis (to detect liver and kidney dysfunction). Differential diagnosis of acute lymphoblastic leukemia is carried out with other leukemias, poisoning, conditions in severe infectious diseases, infectious lymphocytosis and infectious mononucleosis.
Treatment and prognosis
The basis of therapy is chemotherapy drugs. There are two stages of ALL treatment: the intensive therapy stage and the maintenance therapy stage. The stage of intensive therapy of acute lymphoblastic leukemia includes two phases and lasts about six months. In the first phase, intravenous polychemotherapy is performed to achieve remission. The state of remission is indicated by the normalization of hematopoiesis, the presence of no more than 5% of blasts in the bone marrow and the absence of blasts in the peripheral blood. In the second phase, measures are taken to prolong remission, slow down or stop the proliferation of malignant clone cells. The administration of drugs is also carried out intravenously.
The duration of the maintenance therapy stage in acute lymphoblastic leukemia is about 2 years. During this period, the patient is discharged for outpatient treatment, medications are prescribed for oral administration, regular examinations are carried out to monitor the condition of the bone marrow and peripheral blood. The treatment plan for acute lymphoblastic leukemia is made individually, taking into account the level of risk in a particular patient. Along with chemotherapy, immunochemotherapy, radiotherapy and other techniques are used. With low effectiveness of treatment and a high risk of relapse, bone marrow transplantation is performed. The average five-year survival rate for B–cell acute lymphoblastic leukemia in childhood is 80-85%, in adults – 35-40%. With T-lymphoblastic leukemia, the prognosis is less favorable.