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Acute Leukemia Overview
Acute leukemia occurs when a hematopoietic stem cell undergoes malignant transformation into a primitive, undifferentiated cell with abnormal longevity.
These lymphoid cells (acute lymphocytic leukemia [ALL]—see Acute Lymphocytic Leukemia (ALL)) or myeloid cells (acute myelogenous leukemia [AML]—see Acute Myelogenous Leukemia (AML)) proliferate, replacing normal marrow tissue and hematopoietic cells and inducing anemia, thrombocytopenia, and granulocytopenia. Because they are bloodborne, they can infiltrate various organs and sites, including the liver, spleen, lymph nodes, CNS, kidneys, and gonads.
Symptoms may be present for only days to weeks before diagnosis. Disrupted hematopoiesis leads to the most common presenting symptoms (anemia, infection, easy bruising and bleeding). Other presenting symptoms and signs are usually nonspecific (eg, pallor, fatigue, fever, malaise, weight loss, tachycardia, chest pain) and are attributable to anemia and a hypermetabolic state. The cause of fever often is not found, although granulocytopenia may lead to a rapidly progressing and potentially life-threatening bacterial infection. Bleeding is usually manifested by petechiae, easy bruising, epistaxis, bleeding gums, or menstrual irregularity. Hematuria and GI bleeding are uncommon. Bone marrow and periosteal infiltration may cause bone and joint pain, especially in children with ALL. Initial CNS involvement or leukemic meningitis (manifesting as headaches, vomiting, irritability, cranial nerve palsies, seizures, and papilledema) is uncommon. Extramedullary infiltration by leukemic cells may cause lymphadenopathy, splenomegaly, hepatomegaly, and leukemia cutis (a raised, nonpruritic rash). Gum hyperplasia may be prominent, particularly in AML.
CBC and peripheral smear are the first tests done; pancytopenia and peripheral blasts suggest acute leukemia. Blast cells in the peripheral smear may approach 90% of WBC count.
Bone marrow examination (aspiration or needle biopsy) is routinely done, although the diagnosis can usually be made from the peripheral smear. Blast cells in the bone marrow are classically between 25 and 95%. Aplastic anemia, viral infections such as infectious mononucleosis, and vitamin B12 and folate deficiency should be considered in the differential diagnosis of severe pancytopenia. Leukemoid reactions to infectious disease (such as TB) can rarely manifest with high blast counts.
Histochemical studies, cytogenetics, immunophenotyping, and molecular biology studies help distinguish the blasts of ALL from those of AML or other disease processes. Specific B-cell, T-cell, and myeloid-antigen monoclonal antibodies, together with flow cytometry, are essential in classifying the acute leukemias, which is critical for treatment.
Other laboratory findings may include hyperuricemia, hyperphosphatemia, hyperkalemia or hypokalemia, hypocalcemia, elevated serum hepatic transaminases or LDH, hypoglycemia, and hypoxia.
CT of the head is done in patients with CNS symptoms. Chest x-ray should be done to detect mediastinal masses, especially before the patient is given anesthesia. CT, MRI, or abdominal ultrasonography may help assess splenomegaly or leukemic infiltration of other organs.
Cure is a realistic goal for both ALL and AML, especially in younger patients. Prognosis is worse in infants and the elderly and in those with hepatic or renal dysfunction, CNS involvement, testicular involvement, myelodysplasia, or a high WBC count (>25,000/μL). Survival in untreated acute leukemia generally is 3 to 6 mo. Prognosis varies according to multiple variables including patient age, karyotype, response to therapy, and performance status.
The goal of treatment is complete remission, including resolution of abnormal clinical features, restoration of normal blood counts and normal hematopoiesis with < 5% blast cells in the bone marrow, and elimination of the leukemic clone. Although basic principles in treating ALL and AML are similar, the drug regimens differ. The complex nature of patients’ clinical situations and the available treatment protocols necessitate an experienced team. Whenever possible, patients should be treated at specialized medical centers, particularly during critical phases (eg, remission induction).
Supportive care is similar in the acute leukemias and may include
Transfusions of platelets, RBCs, and granulocytes are administered as needed to patients with bleeding, anemia, and neutropenia, respectively. Prophylactic platelet transfusion is done when platelets fall to <10,000/μL; a higher threshold (20,000/μL) is used for patients with the triad of fever, disseminated intravascular coagulation, and mucositis secondary to chemotherapy. Anemia (Hb < 8 g/dL) is treated with transfusions of packed RBCs. Granulocyte transfusions may help neutropenic patients with gram-negative or other serious infections but have no proven benefit as prophylaxis.
Antimicrobials are often needed because patients are neutropenic and immunosuppressed; in such patients, infections can progress quickly with little clinical prodrome. After appropriate studies and cultures have been done, febrile patients with neutrophil counts < 500/μL should begin treatment with a broad-spectrum bactericidal antibiotic that is effective against gram-positive and gram-negative organisms (eg, ceftazidime, imipenem, cilastatin). Fungal infections, especially pneumonias, are becoming more common; these are difficult to diagnose, so chest CT should be done early (ie, < 72 h, depending on degree of suspicion) to detect fungal pneumonia. Empiric antifungal therapy should be given if antibacterial therapy is not effective within 72 h. In patients with refractory pneumonitis, Pneumocystis jirovecii infection or a viral infection should be suspected and confirmed by bronchoscopy and bronchoalveolar lavage and treated appropriately. Empiric therapy with trimethoprim/sulfamethoxazole (TMP/SMX), amphotericin B, and acyclovir or other analogs, often with granulocyte transfusions, is often necessary. In patients with drug-induced immunosuppression at risk of opportunistic infections, TMP/SMX is given to prevent P. jirovecii pneumonia.
Hydration (twice the daily maintenance volume), urine alkalinization (pH 7 to 8), and electrolyte monitoring can prevent the hyperuricemia, hyperphosphatemia, hypocalcemia, and hyperkalemia (tumor lysis syndrome—see Management of Adverse Effects of Cancer Therapy : Tumor Lysis Syndrome) caused by the rapid lysis of leukemic cells during initial therapy (particularly in ALL). Hyperuricemia can be minimized by reducing the conversion of xanthine to uric acid by giving allopurinol (a xanthine oxidase inhibitor) or rasburicase (a recombinant urate-oxidase enzyme) before starting chemotherapy.
Psychologic support may help patients and their families weather the shock of illness and the rigors of treatment for a potentially life-threatening condition.
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