Chronic lymphocytic leukemia is an oncological disease accompanied by the accumulation of atypical mature B–lymphocytes in the peripheral blood, liver, spleen, lymph nodes and bone marrow. In the initial stages, it is manifested by lymphocytosis and generalized lymphadenopathy. With the progression of this pathology, hepatomegaly and splenomegaly are observed, as well as anemia and thrombocytopenia, manifested by weakness, fatigue, petechial hemorrhages and increased bleeding. There are frequent infections caused by a decrease in immunity. The diagnosis is established on the basis of laboratory tests. Treatment – chemotherapy, bone marrow transplantation.
C91.1 Chronic lymphocytic B-cell leukemia
Chronic lymphocytic leukemia is a disease from the group of non–Hodgkin’s lymphomas. It is accompanied by an increase in the number of morphologically mature, but defective B-lymphocytes. Disease is the most common form of hemoblastosis, accounting for a third of all leukemias diagnosed in the United States and European countries. Men suffer more often than women. The peak incidence occurs at the age of 50-70 years, during this period, about 70% of the total number of chronic lymphocytic leukemia is detected.
Young patients rarely suffer, before the age of 40, the first symptoms of the disease occur in only 10% of patients. In recent years, experts have noted some “rejuvenation” of pathology. The clinical course is very variable, both a prolonged absence of progression and an extremely aggressive variant with a fatal outcome within 2-3 years after diagnosis is possible. There are a number of factors that make it possible to predict the course of the disease. The treatment is carried out by specialists in the field of oncology and hematology.
The causes of the occurrence have not been definitively clarified. Disease is considered to be the only leukemia with an unconfirmed link between the development of the disease and adverse environmental factors (ionizing radiation, contact with carcinogenic substances). Experts believe that the main factor contributing to the development of chronic lymphocytic leukemia is a hereditary predisposition. Typical chromosomal mutations that cause damage to oncogenes at the initial stage of the disease have not yet been identified, but studies confirm the mutagenic nature of the disease.
The clinical picture of chronic lymphocytic leukemia is caused by lymphocytosis. The cause of lymphocytosis is the appearance of a large number of morphologically mature, but immunologically defective B-lymphocytes, unable to provide humoral immunity. Previously, it was believed that abnormal B-lymphocytes in chronic lymphocytic leukemia are long-living cells and rarely undergo division. Subsequently, this theory was refuted.
Studies have shown that B-lymphocytes multiply rapidly. Every day, 0.1-1% of the total number of atypical cells is formed in the patient’s body. Different clones of cells are affected in different patients, so chronic lymphocytic leukemia can be considered as a group of closely related diseases with a common etiopathogenesis and similar clinical symptoms.
When studying cells, a wide variety is revealed. The material may be dominated by broad-plasma or narrow-plasma cells with young or wrinkled nuclei, almost colorless or brightly colored granular cytoplasm. The proliferation of abnormal cells occurs in pseudofollicules – clusters of leukemic cells located in lymph nodes and bone marrow.
The causes of cytopenia are autoimmune destruction of blood cells and suppression of stem cell proliferation caused by an increase in the level of T-lymphocytes in the spleen and peripheral blood. In addition, in the presence of killer properties, atypical B lymphocytes can cause the destruction of blood cells.
Taking into account the symptoms, morphological signs, the rate of progression and the response to therapy, the following forms of the disease are distinguished:
- Chronic lymphocytic leukemia with a benign course. The patient’s condition remains satisfactory for a long time. There is a slow increase in the number of leukocytes in the blood. From the moment of diagnosis to a stable increase in lymph nodes, it may take several years or even decades. Patients retain their ability to work and their habitual way of life.
- Classical (progressive) form. Leukocytosis increases over months, not years. There is a parallel increase in lymph nodes.
- The tumor form of chronic lymphocytic leukemia. A distinctive feature of this form is mild leukocytosis with a pronounced increase in lymph nodes.
- Bone marrow form. Progressive cytopenia is detected in the absence of enlargement of the lymph nodes, liver and spleen.
- Chronic lymphocytic leukemia with enlarged spleen.
- Chronic lymphocytic leukemia with paraproteinemia. There are symptoms of one of the above forms of the disease in combination with monoclonal G- or M-gammapathy.
- The pre-lymphocytic form. A distinctive feature of this form is the presence of lymphocytes containing nucleols in blood and bone marrow smears, spleen and lymph node tissue samples.
- Hairy cell leukemia. Cytopenia and splenomegaly are detected in the absence of enlarged lymph nodes. Microscopic examination reveals lymphocytes with a characteristic “youthful” nucleus and “uneven” cytoplasm with breaks, scalloped edges and sprouts in the form of hairs or villi.
- T-cell form. It is observed in 5% of cases. Accompanied by leukemic infiltration of the dermis. Usually progresses rapidly.
There are three stages of clinical stages of chronic lymphocytic leukemia: initial, expanded clinical manifestations and terminal.
At the initial stage, the pathology is asymptomatic and can only be detected by blood tests. For several months or years, a patient with chronic lymphocytic leukemia has lymphocytosis of 40-50%. The number of leukocytes is close to the upper limit of the norm. In the normal state, the peripheral and visceral lymph nodes are not enlarged. During the period of infectious diseases, lymph nodes may temporarily increase, and after recovery they may decrease again. The first sign of the progression of chronic lymphocytic leukemia is a stable increase in lymph nodes, often in combination with hepatomegaly and splenomegaly.
First, the cervical and axillary lymph nodes are affected, then the nodes in the mediastinum and abdominal cavity, then in the inguinal region. Palpation reveals mobile painless dense-elastic formations that are not soldered to the skin and nearby tissues. The diameter of the nodes in chronic lymphocytic leukemia can range from 0.5 to 5 centimeters or more. Large peripheral lymph nodes may bulge with the formation of a visible cosmetic defect. With a significant increase in the liver, spleen and visceral lymph nodes, compression of internal organs may be observed, accompanied by various functional disorders.
Patients with chronic lymphocytic leukemia complain of weakness, unreasonable fatigue and decreased ability to work. According to blood tests, there is an increase in lymphocytosis to 80-90%. The number of red blood cells and platelets usually remains within the normal range, some patients show minor thrombocytopenia. In the late stages of chronic lymphocytic leukemia, weight loss, night sweats and an increase in temperature to subfebrile figures are noted. Immune disorders are characteristic. Patients often suffer from colds, cystitis and urethritis. There is a tendency to suppuration of wounds and frequent formation of ulcers in subcutaneous fat.
The cause of death is often severe infectious diseases. Possible inflammation of the lungs, accompanied by the decline of lung tissue and gross violations of ventilation. Some patients develop exudative pleurisy, which can be complicated by rupture or compression of the thoracic lymphatic duct. Another frequent manifestation of advanced chronic lymphocytic leukemia is shingles, which in severe cases becomes generalized, capturing the entire surface of the skin, and sometimes the mucous membranes. Similar lesions can be observed with herpes and chickenpox.
Among the possible complications is infiltration of the vestibular cochlear nerve, accompanied by hearing disorders and tinnitus. In the terminal stage of chronic lymphocytic leukemia, infiltration of the meninges, medulla and nerve roots may occur. Blood tests reveal thrombocytopenia, hemolytic anemia and granulocytopenia.
It is possible to transform chronic lymphocytic leukemia into Richter syndrome – diffuse lymphoma, manifested by rapid growth of lymph nodes and the formation of foci outside the lymphatic system. About 5% of patients survive until the development of lymphoma. In other cases, death occurs from infectious complications, bleeding, anemia and cachexia. Some patients with chronic lymphocytic leukemia develop severe renal insufficiency due to infiltration of the renal parenchyma.
In half of the cases, pathology is detected by accident, during examination for other diseases or during a routine examination. When making a diagnosis, complaints, anamnesis, objective examination data, results of blood tests and immunophenotyping are taken into account. The diagnostic criterion for chronic lymphocytic leukemia is an increase in the number of leukocytes in the blood test to 5 ×109 / l in combination with characteristic changes in the immunophenotype of lymphocytes. Microscopic examination of a blood smear reveals small B-lymphocytes and Gumprecht shadows, possibly in combination with atypical or large lymphocytes. Immunophenotyping confirms the presence of cells with an aberrant immunophenotype and clonality.
Determination of the stage of chronic lymphocytic leukemia is carried out on the basis of clinical manifestations of the disease and the results of an objective examination of peripheral lymph nodes. Cytogenetic studies are carried out to draw up a treatment plan and assess the prognosis for chronic lymphocytic leukemia. If Richter syndrome is suspected, a biopsy is prescribed. To determine the causes of cytopenia, a sternal puncture of the bone marrow is performed, followed by microscopic examination of the punctate.
In the initial stages of chronic lymphocytic leukemia, wait-and-see tactics are used. Patients are prescribed an examination every 3-6 months. In the absence of signs of progression, they are limited to observation. The indication for active treatment is an increase in the number of white blood cells by half or more within six months. The main method of treatment of chronic lymphocytic leukemia is chemotherapy. The most effective combination of drugs is usually a combination of rituximab, cyclophosphamide and fludarabine.
With a persistent course of chronic lymphocytic leukemia, large doses of corticosteroids are prescribed, bone marrow transplantation is performed. In elderly patients with severe somatic pathology, the use of intensive chemotherapy and bone marrow transplantation may be difficult. In such cases, monochemotherapy with chlorambucil is performed or this drug is used in combination with rituximab.
In chronic lymphocytic leukemia with autoimmune cytopenia, prednisone is prescribed. Treatment is carried out until the patient’s condition improves, while the duration of the course of therapy is at least 8-12 months. After a stable improvement in the patient’s condition, treatment is discontinued. The indication for the resumption of therapy is clinical and laboratory symptoms, indicating the progression of the disease.
Chronic lymphocytic leukemia is considered as an almost incurable long-term disease with a relatively satisfactory prognosis. In 15% of cases, there is an aggressive course with a rapid increase in leukocytosis and progression of clinical symptoms. The fatal outcome in this form of chronic lymphocytic leukemia occurs within 2-3 years. In other cases, there is a slow progression, the average life expectancy from the moment of diagnosis ranges from 5 to 10 years. With a benign course, the life span can be several decades. After undergoing treatment, improvement is observed in 40-70% of patients with chronic lymphocytic leukemia, but complete remissions are rarely detected.