Chronic leukemia is a primary tumor disease of the hematopoiesis system, the substrate of which is mature and maturing cells of the myeloid or lymphoid series. Various forms occur with a predominance of intoxication (weakness, arthralgia, ossalgia, anorexia, weight loss), thrombohemorrhagic (bleeding, thrombosis of various localization), lymphoproliferative syndromes (enlarged lymph nodes, splenomegaly, etc.). Crucial in the diagnosis belongs to the analysis of blood, bone marrow biopsies and lymph nodes. Treatment is carried out by methods of chemotherapy, radiation therapy, immunotherapy, bone marrow transplantation is possible.
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Chronic leukemia is a chronic lymphoproliferative and myeloproliferative diseases characterized by an excessive increase in the number of hematopoietic cells that retain the ability to differentiate. Unlike acute leukemias, in which low-grade hematopoietic cells proliferate, in disease, the tumor substrate is represented by maturing or mature cells. All types of this disease are characterized by a long stage of benign monoclonal tumor.
Pathology affects mainly adults aged 40-50 years; men get sick more often. The share of chronic lymphoid leukemia accounts for about 30% of cases, chronic myeloid leukemia – 20% of all forms of leukemia. Chronic lymphocytic leukemia in hematology is diagnosed 2 times more often than chronic myeloid leukemia. Leukemias in children occur in a chronic form extremely rarely – in 1-2% of cases.
The true causes leading to the development of disease are unknown. Currently, the viral-genetic theory of hemoblastosis has received the greatest recognition. According to this hypothesis, some types of viruses (including Ebstein–Barr virus, retroviruses, etc.) are able to penetrate immature hematopoietic cells and cause their unhindered division.
The role of heredity in the origin of leukemia is also not in doubt, since it is known for certain that the disease is often of a family nature. In addition, chronic myeloid leukemia in 95% of cases is associated with an anomaly of the 22nd chromosome (Philadelphia or Ph chromosome), a fragment of the long arm of which is translocated to the 9th chromosome.
The most significant predisposing factors to various types and forms are the effects on the body:
- high doses of radiation;
- x-ray irradiation;
- industrial chemical hazards (varnishes, paints, etc.);
- medicines (gold salts, antibiotics, cytostatics);
- long smoking experience.
The risk of developing chronic lymphocytic leukemia increases with prolonged contact with herbicides and pesticides, and chronic myeloid leukemia increases with radiation exposure.
Immunological mechanisms play a significant role in the pathogenesis of chronic lymphocytic leukemia, as evidenced by its frequent combination with autoimmune hemolytic anemia and thrombocytopenia, collagenoses. However, in most patients with this pathology, causally significant factors cannot be identified.
Depending on the origin and cellular substrate of the tumor, disease are divided into:
- Lymphocytic: chronic lymphocytic leukemia, Cesari’s disease (skin lymphomatosis), hairy cell leukemia, paraproteinemic hemoblastosis (myeloma, Waldenstrom’s macroglobulinemia, light chain diseases, heavy chain diseases).
- Myelocytic (granulocytic): chronic myeloid leukemia, erythremia, true polycythemia, chronic erythromyelosis, etc.
- Monocytic: chronic monocytic leukemia and histiocytosis.
In its development, the tumor process in chronic leukemia goes through two stages: monoclonal (benign) and polyclonal (malignant). The course is conditionally divided into 3 stages: initial, expanded and terminal.
Chronic myeloid leukemia
In the initial period of chronic myeloid leukemia, clinical manifestations are absent or non-specific, hematological changes are detected by chance during a blood test. In the preclinical period, there may be an increase in weakness, adynamia, sweating, subfebrility, pain in the left hypochondrium.
The transition of disease to the advanced stage is marked by progressive hyperplasia of the spleen and liver, anorexia, weight loss, severe bone pain and arthralgia. The formation of leukemic infiltrates on the skin, oral mucosa (leukemic periodontitis), gastrointestinal tract is characteristic. Hemorrhagic syndrome is manifested by hematuria, menorrhagia, metrorrhagia, bleeding after tooth extraction, bloody diarrhea. In the case of secondary infection (pneumonia, tuberculosis, sepsis, etc.), the temperature curve acquires a hectic character.
The terminal stage proceeds with a sharp exacerbation of all symptoms and pronounced intoxication. During this period, a poorly treatable and life–threatening condition may develop – a blast crisis, when due to a sharp increase in the number of blast cells, the course of the disease becomes similar to acute leukemia. Blast crisis is characterized by aggressive symptoms: skin leukemias, severe bleeding, secondary infections, high fever, possible rupture of the spleen.
Chronic lymphocytic leukemia
For a long time, the only sign of chronic lymphocytic leukemia may be lymphocytosis up to 40-50%, a slight increase in one or two groups of lymph nodes. During the expanded period, lymphadenitis takes a generalized form: not only peripheral, but also mediastinal, mesenteric, retroperitoneal nodes increase. Splenic and hepatomegaly occur; possible compression of the choledochus by enlarged lymph nodes with the development of jaundice, as well as the superior vena cava with the development of edema of the neck, face, hands (ERW syndrome). They are worried about persistent ossalgia, itching, recurrent infections.
The severity of the general condition of patients is due to the progression of intoxication (weakness, sweating, fever, anorexia) and anemic syndrome (dizziness, shortness of breath, palpitations, fainting).
The terminal stage is characterized by the addition of hemorrhagic and immunodeficiency syndromes. During this period, severe intoxication develops, hemorrhages under the skin and mucous membranes, nasal, gingival, uterine bleeding occur.
Immunodeficiency caused by the inability of functionally immature leukocytes to perform their protective functions is manifested by the syndrome of infectious complications. Patients with chronic lymphocytic leukemia often have lung infections (bronchitis, bacterial pneumonia, tuberculous pleurisy), fungal lesions of the skin and mucous membranes, abscesses and phlegmons of soft tissues, pyelonephritis, herpes infection, sepsis.
Dystrophic changes of internal organs, cachexia, renal insufficiency are increasing. The fatal outcome in chronic lymphoid leukemia comes from severe infectious-septic complications, bleeding, anemia, exhaustion. The transformation of chronic lymphocytic leukemia into acute leukemia or lymphosarcoma (non-Hodgkin’s lymphoma) is possible.
The presumed diagnosis is established on the basis of a hemogram analysis, with the results of which the patient should be immediately referred to a hematologist. To confirm the diagnosis is carried out:
- Blood test. Typical changes for chronic myeloid leukemia include: anemia, the presence of single myeloblasts and granulocytes at different stages of differentiation; during the blast crisis, the number of blast cells increases by more than 20%. In chronic lymphocytic leukemia, the defining hematological signs are pronounced leukocytosis and lymphocytosis, the presence of lymphoblasts and Botkin-Gumprecht cells.
- Punctures and biopsies. In order to determine the morphology of the tumor substrate, sternal puncture, trepanobiopsy, and lymph node biopsy were performed. In the bone marrow punctate in chronic myeloid leukemia, the number of myelocaryocytes is increased due to immature granulocyte cells; in the trepanobioptate, the replacement of adipose tissue with myeloid is determined. In chronic lymphoid leukemia, the myelogram is characterized by a sharp increase in lymphocytic metaplasia.
- Instrumental research. To assess the severity of lymphoproliferative syndrome, ultrasound of the lymph nodes, spleen, chest X-ray, lymphoscintigraphy, abdominal MSCT and a number of others are used.
At the early preclinical stage, treatment is ineffective, so patients are subject to dynamic monitoring. General winter activities involve the exclusion of physical overload, stress, insolation, electrical procedures and heat treatment; full-fledged fortified nutrition, long walks in the fresh air.
In the expanded period of myeloid leukemia, chemotherapeutic treatment is prescribed (busulfan, mitobronitol, hydroxyurea, etc.), with pronounced splenomegaly, the spleen is irradiated. This tactic, although it does not lead to a complete cure, but significantly slows down the progression of the disease and allows you to delay the onset of a blast crisis. In addition to drug therapy, leukapheresis procedures are used for chronic myelocytic leukemia. In some cases, the cure is achieved with the help of bone marrow transplantation.
During the transition of chronic myeloid leukemia to the terminal stage, high-dose polychemotherapy is prescribed. On average, after diagnosis, patients with chronic myeloid leukemia live 3-5 years, in some cases – 10-15 years. Cytostatic therapy (chlorbutin, cyclophosphamide) is also performed, sometimes in combination with steroid therapy, irradiation of lymph nodes, spleen, skin. With a significant increase in the spleen, splenectomy is performed. Stem cell transplantation is used, but its effectiveness still needs to be confirmed.
The life expectancy of patients with chronic lymphoid leukemia can range from 2-3 years (with severe, steadily progressive forms) to 20-25 years (with a relatively favorable course).
- Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in Imatinib-Resistant Philadelphia Chromosome-Positive Leukemias. N Engl J Med. 2006;354(24):2531-41. link
- Cortes J, Rousselot P, Kim D, et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood. 2007;109(8): 3207-13.
- Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354(24):2542-51. link
- Kantarjian H, Giles F, Gattermann N, et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007;110(10):3540-6.
- Khoury J, Cortes JE, Kantarjian H, et al. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood. 2012;119(15):3403-12. link