Acute leukemia

Acute leukemia occurs when a hematopoietic stem cell undergoes malignant transformation into a primitive, undifferentiated cell with an abnormal life span.

Lymphoblasts (ALL) or myeloblasts (AML) exhibit abnormal proliferative capacity, displacing normal bone marrow and hematopoietic cells, inducing anemia, thrombocytopenia, and granulocytopenia. Once 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 usually do not begin until days or weeks before diagnosis. Impaired hematopoiesis causes the most common symptoms (anemia, infections, bruising, and bleeding). Other symptoms and complaints are nonspecific (eg, pallor, weakness, malaise, weight loss, tachycardia, chest pain) and are due to the anemia and hypermetabolic state. The cause of fever is usually unknown, although granulocytopenia may lead to rapidly progressive and potentially life-threatening bacterial infections. Bleeding is most often manifested as petechiae, a tendency to bruise, epistaxis, bleeding gums, or irregular menstruation. Hematuria and gastrointestinal bleeding are less common. Infiltration of the bone marrow and periosteum may cause ossalgias and arthralgias, especially in children with acute lymphoblastic leukemia. Primary central nervous system involvement or leukemic meningitis (manifested by headaches, nausea, irritability, cranial nerve palsies, seizures, and papilledema) is rare. Extramedullary infiltration by leukemic cells may result in lymphadenopathy, splenomegaly, hepatomegaly, and leukemids (areas of elevated skin or nonpruritic skin rash).

Diagnosis of acute leukemia

The first tests to be performed are a complete blood count and a peripheral blood smear. 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 from a peripheral blood smear, a bone marrow examination (aspiration or fine-needle biopsy) should be performed. Blasts in the bone marrow make up from 30 to 95%. In the differential diagnosis of severe pancytopenia, it is necessary to keep in mind such disorders as aplastic anemia, vitamin B ₁₂ and folate deficiency, viral infections (such as infectious mononucleosis) and leukemoid reactions in infectious diseases (such as tuberculosis), which can manifest as an increased 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. Flow cytometry with analysis of monoclonal antibodies specific to B- and T-lymphocytes, myeloid cells helps in differentiating leukemias, which is the main point for choosing treatment.

Other laboratory abnormalities may include hyperuricemia, hyperphosphatemia, hyperkalemia or hypokalemia, elevated liver transaminases or serum lactate dehydrogenase, hypoglycemia, and hypoxia. Lumbar puncture and computed tomography of the head are performed in patients with symptoms of central nervous system involvement, B-cell acute lymphoblastic leukemia, high white blood cell count, or high lactate dehydrogenase. Chest radiography is performed if a mass lesion is present in the mediastinum, and computed tomography may be performed in addition. Magnetic resonance imaging, computed tomography, and ultrasound can be used to evaluate the extent of splenic involvement and leukemic infiltration of other organs.

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Treatment of acute leukemia

The goal of treatment is to achieve complete remission, including resolution of clinical symptoms, normalization of blood cell counts, normalization of hematopoiesis with blast counts of less than 5%, and elimination of the leukemic clone. Although the basic principles of treatment for acute lymphoblastic and myeloblastic leukemia are similar, chemotherapy regimens differ. The need for a comprehensive approach that takes into account the clinical characteristics of the patient and existing treatment protocols requires the participation of experienced specialists in therapy. Treatment, especially during critical periods (e.g., remission induction), should be performed in a specialized medical center.

Maintenance treatment of acute leukemia

Bleeding is often a consequence of thrombocytopenia and usually resolves with platelet transfusion. Prophylactic platelet transfusions are given when the platelet count falls below 10,000/μl; a higher cutoff of less than 20,000/μl is used in patients with a triad of symptoms including fever, disseminated intravascular coagulation, and postchemotherapy mucositis. Anemia (hemoglobin level below 80 g/l) is treated with red blood cell transfusions.

Neutropenic, immunosuppressed patients have severe infections that may progress rapidly without the usual clinical features. After appropriate testing and cultures, patients with or without fever and a neutrophil count of less than 500/mm3 should be treated with broad-spectrum antibiotics that cover both gram-positive and gram-negative organisms (eg, ceftazidime, imipenem, cilastatin). Fungal infections, especially pneumonias, are common and difficult to diagnose, so if antibiotics are ineffective within 72 hours, empirical antifungal therapy should be initiated. In patients with refractory pneumonitis, Pneumocystis jiroveci (formerly P. carinii) or a viral infection should be considered and bronchoscopy, bronchoalveolar lavage, and appropriate treatment should be performed. Empirical therapy with trimethoprim-sulfamethoxazole (TMP-SMX), amphotericin, and acyclovir or their analogs, often with granulocyte transfusions, is often necessary. Granulocyte transfusions may be useful in patients with neutropenia and gram-negative or other serious sepsis, but their effectiveness as a prophylactic agent has not been established. In patients with drug-induced immunosuppression and risk of opportunistic infection, TMP-SMX should be given for prophylaxis against P. jiroveci pneumonia.

Rapid lysis of leukemic cells early in therapy (especially in acute lymphoblastic leukemia) may cause hyperuricemia, hyperphosphatemia, and hyperkalemia (tumor lysis syndrome). Prevention of this syndrome includes increased hydration (doubling the daily volume of fluid consumed), alkalinization of urine (pH 7-8), and monitoring of electrolytes. Hyperuricemia can be reduced by administering allopurinol (a xanthine oxidase inhibitor) or rasburicase (a recombinant urate oxidase) before chemotherapy to reduce the conversion of xanthine to uric acid.

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

Prognosis for acute leukemia

Cure is a realistic goal in acute lymphoblastic and myeloid leukemia, especially in young patients. In infants and older patients, as well as in patients with liver or kidney dysfunction, central nervous system involvement, myelodysplasia, or high leukocytosis (> 25,000/μL), the prognosis is poor. Survival in untreated patients is usually 3 to 6 months. The prognosis varies depending on the karyotype.