Leukemia is a malignant lesion of bone marrow tissue that leads to impaired maturation and differentiation of hematopoietic cells–precursors of leukocytes, their uncontrolled growth and dissemination throughout the body in the form of leukemic infiltrates. Symptoms can be weakness, weight loss, fever, bone pain, causeless hemorrhages, lymphadenitis, splenic and hepatomegaly, meningeal symptoms, frequent infections. The diagnosis is confirmed by a blood test, sternal puncture with bone marrow examination, trepanobiopsy. Treatment requires long-term continuous polychemotherapy, symptomatic therapy, and, if necessary, bone marrow or stem cell transplantation.
Leukemia (blood cancer, white blood) is a tumor disease of the hematopoietic system (hemoblastosis) associated with the replacement of healthy specialized leukocyte cells with abnormally altered leukemic cells. Leukemia is characterized by rapid expansion and systemic damage to the body – hematopoietic and circulatory systems, lymph nodes and lymphoid formations, spleen, liver, central nervous system, etc. Leukemia affects both adults and children, is the most common childhood cancer. Men get sick 1.5 times more often than women.
Leukemic cells are not capable of full differentiation and the performance of their functions, but at the same time have a longer lifespan, a high potential for division. Leukemia is accompanied by a gradual displacement of populations of normal leukocytes (granulocytes, monocytes, lymphocytes) and their precursors, as well as a deficiency of platelets and erythrocytes. This is facilitated by the active self-reproduction of leukemic cells, their higher sensitivity to growth factors, the release of a growth stimulator of tumor cells and factors that inhibit normal hematopoiesis.
According to the peculiarities of development, acute and chronic leukemia are distinguished. In acute leukemia (50-60% of all cases), there is a rapid progressive growth of a population of poorly differentiated blast cells that have lost the ability to mature. Taking into account their morphological, cytochemical, immunological signs, acute leukemia is divided into lymphoblastic, myeloblastic and undifferentiated forms.
Acute lymphoblastic leukemia (ALL) – accounts for up to 80-85% of cases of leukemia in children, mainly at the age of 2-5 years. The tumor is formed along the lymphoid line of hematopoiesis and consists of lymphocyte precursors – lymphoblasts (L1, L2, L3 types) belonging to a B-cell, T-cell or O-cell proliferative germ.
Acute myeloblastic leukemia (AML) is the result of damage to the myeloid line of hematopoiesis; leukemic growths are based on myeloblasts and their descendants, other types of blast cells. In children, the proportion of AML is 15% of all leukemias, with age there is a progressive increase in the frequency of the disease. Several variants of AML are distinguished – with minimal signs of differentiation (M0), without maturation (M1), with signs of maturation (M2), promyelocytic (M3), myelomonoblastic (M4), monoblastic (M5), erythroid (M6) and megakaryocytic (M7).
Undifferentiated leukemia is characterized by the growth of early progenitor cells without signs of differentiation, represented by homogeneous small pluripotent blood stem cells or partially determined semi-stem cells.
The chronic form of leukemia is recorded in 40-50% of cases, it is most common among the adult population (40-50 years and older), especially among people exposed to ionizing radiation. Chronic leukemia develops slowly, over several years, manifested by an excessive increase in the number of mature, but functionally inactive, long–lived leukocytes – B and T-lymphocytes in the lymphocytic form (CLL) and granulocytes and maturing myeloid progenitor cells in the myelocytic form (CML). Juvenile, child and adult variants of CML, erythremia, myeloma (plasmocytoma) are isolated separately. Erythremia is characterized by leukemic transformation of erythrocytes, high neutrophilic leukocytosis and thrombocytosis. The source of myeloma is tumor growth of plasmocytes, disorders of Ig metabolism.
The cause of leukemia is intra- and interchromosomal aberrations – violations of the molecular structure or the exchange of chromosome sites (deletions, inversions, fragmentation and translocation). For example, in chronic myeloid leukemia, the appearance of the Philadelphia chromosome with translocation t (9;22) is observed. Leukemic cells can occur at any stage of hematopoiesis. At the same time, chromosomal disorders can be primary – with a change in the properties of the hematopoietic cell and the creation of its specific clone (monoclonal leukemia) or secondary, arising during the proliferation of a genetically unstable leukemic clone (a more malignant polyclonal form).
Leukemia is more often detected in patients with chromosomal diseases (Down syndrome, Klinefelter syndrome), primary immunodeficiency conditions. Infection with oncogenic viruses can be attributed to a possible cause of leukemia. The disease is facilitated by the presence of a hereditary predisposition, since it is more common in families with leukemia patients.
Malignant transformation of hematopoietic cells can occur under the influence of various mutagenic factors: ionizing radiation, high voltage electromagnetic field, chemical carcinogens (drugs, pesticides, cigarette smoke). Secondary leukemia is often associated with radiation or chemotherapy during the treatment of other oncopathology.
The course of leukemia goes through several stages: initial, expanded manifestations, remission, recovery, relapse and terminal. The symptoms of leukemia are nonspecific and have common features in all types of the disease. They are determined by tumor hyperplasia and infiltration of the bone marrow, circulatory and lymphatic systems, central nervous system and various organs; deficiency of normal blood cells; hypoxia and intoxication, the development of hemorrhagic, immune and infectious consequences. The degree of manifestation of leukemia depends on the localization and massiveness of the leukemic lesion of hematopoiesis, tissues and organs.
With acute leukemia, general malaise, weakness, decreased appetite and weight loss, and pallor of the skin quickly appear and increase. Patients are concerned about high fever (39-40 ° C), chills, arthralgia and bone pain; easily occurring bleeding of the mucous membranes, skin hemorrhages (petechiae, bruises) and bleeding of different localization.
There is an increase in regional lymph nodes (cervical, axillary, inguinal), swelling of the salivary glands, hepatomegaly and splenomegaly are observed. Infectious and inflammatory processes of the oropharyngeal mucosa – stomatitis, gingivitis, ulcerative necrotic sore throat – often develop resistant to treatment. Anemia, hemolysis are detected, DIC syndrome may develop.
For neuroleukemia, meningeal symptoms (vomiting, severe headaches, swelling of the optic nerve, convulsions), pain in the spine, paresis, paralysis are indicative. With ALL, massive blast lesions of all groups of lymph nodes, thymus gland, lungs, mediastinum, gastrointestinal tract, kidneys, genitals develop; with AML, multiple myelosarcomas (chloromas) in the periosteum, internal organs, adipose tissue, on the skin. In elderly patients with leukemia, angina pectoris, cardiac arrhythmia are possible.
Chronic leukemia has a slowly or moderately progressive course (from 4-6 to 8-12 years); typical manifestations of the disease are observed in the advanced stage (acceleration) and terminal (blast crisis), when blast cells metastasize outside the bone marrow. Against the background of exacerbation of general symptoms, there is a sharp exhaustion, an increase in the size of internal organs, especially the spleen, generalized lymphadenitis, pustular skin lesions (pyoderma), pneumonia.
In the case of erythremia, vascular thrombosis of the lower extremities, cerebral and coronary arteries appear. Myeloma occurs with single or multiple tumor infiltrates of the bones of the skull, spine, ribs, shoulder, hip; osteolysis and osteoporosis, bone deformity and frequent fractures accompanied by pain syndrome. Sometimes AL-amyloidosis, myeloma nephropathy with CRF develops.
The death of a patient with leukemia can occur at any stage due to extensive hemorrhages, hemorrhages in vital organs, rupture of the spleen, the development of purulent-septic complications (peritonitis, sepsis), severe intoxication, renal and heart failure.
As part of diagnostic studies for leukemia, general and biochemical blood analysis, diagnostic puncture of the bone marrow (sternal) and spinal cord (lumbar), trepanobiopsy and biopsy of lymph nodes, radiography, ultrasound, CT and MRI of vital organs are performed.
In peripheral blood, severe anemia, thrombocytopenia, a change in the total number of leukocytes (usually an increase, but a deficiency is also possible), a violation of the leukocyte formula, the presence of atypical cells are observed. In acute leukemia, blasts and a small percentage of mature cells without transitional elements are determined (“leukemic failure”), in chronic – bone marrow cells of different classes of development.
The key in leukemia is the examination of bone marrow biopsies (myelogram) and cerebrospinal fluid, including morphological, cytogenetic, cytochemical and immunological analyses. This makes it possible to clarify the forms and subtypes of leukemia, which is important for choosing a treatment protocol and predicting the disease. In acute leukemia, the level of undifferentiated blasts in the bone marrow is more than 25%. An important criterion is the detection of the Philadelphia chromosome (Ph chromosome).
Leukemic infiltration of internal organs is established by ultrasound of the lymph nodes, abdominal cavity and pelvis, chest X-ray, skull, bones and joints, chest CT, MRI of the brain and spinal cord with contrast, EchoCG. With leukemia, consultation with an otolaryngologist, neurologist, urologist, ophthalmologist is indicated.
Leukemia is differentiated from autoimmune thrombocytopenic purpura, neuroblastoma, juvenile rheumatoid arthritis, infectious mononucleosis, as well as other tumor and infectious diseases that cause a leukemoid reaction.
Treatment of leukemia is carried out by hematologists in specialized oncohematological clinics in accordance with accepted protocols, in compliance with clearly established deadlines, main stages and volumes of therapeutic and diagnostic measures for each form of the disease. The goal of leukemia treatment is to obtain a long–term complete clinical and hematological remission, restore normal hematopoiesis and prevent relapses, and, if possible, complete cure of the patient.
Acute leukemia requires the immediate initiation of an intensive course of treatment. Multicomponent chemotherapy is used as a basic method for leukemia, to which acute forms are most sensitive (efficacy at ALL – 95%, AML ~ 80%) and childhood leukemias (up to 10 years). To achieve remission of acute leukemia due to reduction and eradication of leukemic cells, combinations of various cytostatic drugs are used. During the period of remission, long-term (for several years) treatment continues in the form of fixing (consolidating), and then supportive chemotherapy with the addition of new cytostatics to the regimens. For the prevention of neuroleukemia during remission, intrathecal and intralumbal local administration of chemotherapy drugs and brain irradiation are indicated.
Treatment of AML is problematic due to the frequent development of hemorrhagic and infectious complications. The promyelocytic form of leukemia is more favorable, which goes into complete clinical and hematological remission under the action of promyelocyte differentiation stimulators. In the stage of complete remission of AML, allogeneic bone marrow transplantation (or the introduction of stem cells) is effective, allowing in 55-70% of cases to achieve 5-year survival without relapse.
With chronic leukemia in the preclinical stage, constant monitoring and general restorative measures (a full diet, a rational work and rest regime, exclusion of insolation, physiotherapy) are sufficient. Outside of exacerbation of chronic leukemia, substances that block the tyrosine kinase activity of the Bcr-Abl protein are prescribed; but they are less effective during the acceleration phase and blast crisis. In the first year of the disease, it is advisable to introduce a-interferon. In CML, allogeneic bone marrow transplantation from a related or unrelated HLA donor can give good results (60% of cases of complete remission within 5 years or more). In case of exacerbation, mono- or polychemotherapy is immediately prescribed. It is possible to use irradiation of lymph nodes, spleen, skin; and for certain indications – splenectomy.
Hemostatic and detoxification therapy, platelet and leukocyte mass infusions, and antibiotic therapy are used as symptomatic measures for all forms of leukemia.
The prognosis of leukemia depends on the form of the disease, the prevalence of the lesion, the patient’s risk group, the timing of diagnosis, response to treatment, etc. Leukemia has a poorer prognosis in male patients, in children over the age of 10 and adults over 60; with a high level of leukocytes, the presence of the Philadelphia chromosome, neuroleukemia; in cases of delayed diagnosis. Acute leukemias have a much worse prognosis due to the rapid course and, if left untreated, quickly lead to death. In children, with timely and rational treatment, the prognosis of acute leukemia is more favorable than in adults. A good prognosis of leukemia is the probability of 5-year survival of 70% or more; the risk of relapse is less than 25%.
Chronic leukemia, upon reaching a blast crisis, acquires an aggressive course with a risk of death due to the development of complications. With proper treatment of the chronic form, it is possible to achieve remission of leukemia for many years.
- Modern approach to diagnosis and therapy in childhood leukemias – Hasanbegović E. – Med Arh. 2004;58(1):59-60. link
- The adolescent and young adult with cancer: state of the art– acute leukemias. – Gramatges MM, Rabin KR. – Curr Oncol Rep. 2013 Aug;15(4):317-24. link
- Leukemia can be Effectively Early Predicted in Routine Physical Examination with the Assistance of Machine Learning Models. – Yu C, Peng YY, Liu L, Wang X, Xiao Q. – J Healthc Eng. 2022 Nov 24;2022:8641194. link
- The molecular biology and therapeutic potential of Nrf2 in leukemia. – Khodakarami A, Adibfar S, Karpisheh V, Abolhasani S, Jalali P, Mohammadi H, Gholizadeh Navashenaq J, Hojjat-Farsangi M, Jadidi-Niaragh F. – Cancer Cell Int. 2022 Jul 29;22(1):241 link