Acute leukemia

Acute leukemia is formed by malignant transformation of the hematopoietic stem cell into a primitive undifferentiated cell with an abnormal life span.

Lymphoblasts (ALL) or myeloblasts (AML) exhibit an abnormal proliferative capacity, displacing normal bone marrow tissue and hematopoietic cells, inducing anemia, thrombocytopenia and granulocytopenia. Being in the blood, they can infiltrate various organs and tissues, including the liver, spleen, lymph nodes, central nervous system, kidneys and gonads.

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Symptoms of acute leukemia

Symptoms of the disease usually begin to appear only a few days or weeks before the diagnosis is established. Violation of hemopoiesis causes the most common symptoms (anemia, infection, bruising and bleeding). Other symptoms and complaints are not specific (for example, pallor, weakness, malaise, weight loss, tachycardia, chest pain) and are caused by anemia and hypermetabolic condition. The cause of fever is usually not established, although granulocytopenia can lead to the development of rapidly progressive and potentially life-threatening bacterial infections. Bleeding is more often manifested in the form of petechiae, a tendency to form subcutaneous hemorrhages, nasal bleeding, bleeding gums, or irregular menstruation. Hematuria and gastrointestinal hemorrhages are less common. Infiltration of bone marrow and periosteum can cause ossalgia and arthralgia, especially in children with acute lymphoblastic leukemia. The primary lesion of the central nervous system or leukemic meningitis (manifested by headaches, nausea, irritability, paralysis of the cranial nerves, convulsions and edema of the nipple of the optic nerve) is rare. Extramedullary infiltration with leukemia cells can lead to lymphadenopathy, splenomegaly, hepatomegaly and leukemidae (areas of elevation on the skin or skin rash without itching).

Diagnosis of acute leukemia

First of all, a general clinical blood test and a smear of peripheral blood are performed from the examinations. The presence of pancytopenia and blast cells in the blood indicate acute leukemia. The level of blast forms in the blood can reach 90% against the background of a marked decrease in the total number of leukocytes. Although the diagnosis can often be made on the smear of peripheral blood, bone marrow examination (aspiration or fine needle biopsy) should be performed. The blasts in the bone marrow are from 30 to 95%. When the differential diagnosis of severe pancytopenia necessary to mean such conditions as aplastic anemia, deficiency of vitamin B ₁₂ and folic acid, viral infections (such as infectious mononucleosis) and leukemoid response in infectious diseases (such as tuberculosis), which can manifest in the form of increased the number of blast forms.

Histochemical, cytogenetic studies, immunophenotyping and molecular biological studies help differentiate blasts in acute lymphoblastic leukemia from acute myeloblastic leukemia or other pathological processes. Conducting flow cytometry with analysis for monoclonal antibodies specific for B-and T-lymphocytes, myeloid cells, helps in the differentiation of leukemia, which is the main point for choosing treatment.

Other changes in laboratory indicators may include hyperuricemia, hyperphosphatemia, hyperkalemia or hypokalemia, elevation of hepatic transaminases or lactate dehydrogenase in blood serum, hypoglycemia and hypoxia. Lumbar puncture and computed tomography of the head are performed in patients with symptoms of central nervous system damage, B-cell acute lymphoblastic leukemia, high blood leukocyte count or high lactate dehydrogenase. Radiography of chest organs is performed in the presence of volumetric education in the mediastinum, in addition computer tomography can be made. Evaluate the degree of spleen damage and leukemia infiltration of other organs by methods such as magnetic resonance imaging, computed tomography, ultrasound.

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Treatment of acute leukemia

The goal of treatment is to achieve complete remission, including resolution of clinical symptoms, normalization of the number of blood cells, normalization of hemopoiesis with number of blast forms less than 5%, and elimination of leukemic clone. Although the basic principles of treatment for acute lymphoblastic and myeloblastic leukemia are similar, chemotherapy regimes differ. The need for an integrated approach that takes into account the clinical features of the patient and available treatment protocols requires participation in the therapy of experienced specialists. Treatment, especially in critical periods (eg, induction of remission), should be conducted in a specialized medical center.

Supportive treatment of acute leukemia

Bleeding is often a consequence of thrombocytopenia and is usually eliminated after platelet transfusion. Prophylactic platelet transfusions are performed with a decrease in platelets of less than 10,000 / μL; in patients with a triad of symptoms including fever, dis-seized intravascular coagulation developed after chemotherapy with mucositis, a higher threshold level of less than 20,000 / μl is used. At anemia (hemoglobin level below 80 g / l) transfusions of erythrocyte mass are made.

In patients with neutropenia and immunosuppression, there is a severe course of infections that can quickly progress without manifesting a common clinical picture. After proper tests and culture, patients with or without fever and with less than 500 / μl neutrophils should be prescribed broad-spectrum antibiotics that affect the Gram-positive and Gram-negative flora (eg ceftazidime, imipenem, cilastatin). Often there are fungal infections, especially pneumonia, and their diagnosis is difficult, so if the antibiotic therapy is ineffective within 72 hours, empiric antifungal therapy should be prescribed. Patients with refractory pneumonitis should consider the possibility of Pneumocystis jiroveci (formerly P. Carinii) or a viral infection, for which it is necessary to perform bronchoscopy, bronchoalveolar lavage and prescribe appropriate treatment. Often empirical therapy is required, including trimethoprim-sulfamethoxazole (TMP-SMX), amphotericin and acyclovir or their analogs, often with granulocyte transfusion. Granulocyte transfusions can be useful in patients with neutropenia and Gram-negative or other serious sepsis, but their effectiveness as a prophylactic is not proven. In patients with drug-induced immunosuppression and the risk of opportunistic infection, the prevention of pneumonia caused by P. Jiroveci requires the designation of TMP-SMX.

Rapid lysis of leukemia cells at the beginning of therapy (especially in acute lymphoblastic leukemia) can cause hyperuricemia, hyperphosphatemia and hyperkalemia (tumor lysis syndrome). Prevention of this syndrome includes increased hydration (an increase in the daily intake volume by a factor of 2), alkalinization of urine (pH 7-8), and monitoring of electrolytes. Hyperuricemia can be reduced by taking allopurinol (xanthine oxidase inhibitor) or rasburikazy (recombinant urate oxidase) before starting chemotherapy to reduce the transformation of xanthine to uric acid.

Psychological support can help patients and their families overcome the shock of illness and the difficulties of treating this potentially life-threatening disease.

Prognosis for acute leukemia

Cure is a real goal in acute lymphoblastic and myeloblastic leukemia, especially in young patients. In infants and elderly patients, as well as in patients with impaired liver or kidney function, central nervous system damage, myelodysplasia or high leukocytosis (> 25 000 / μl), the prognosis is unfavorable. Survival in untreated patients is usually from 3 to 6 months. The prognosis varies depending on the karyotype.