A. Symptoms and Signs: Most patients with acute leukemia present with an acute illness and have been ill only for days or weeks. Bleeding (usually due to thrombocytopenia) is usually in the skin and mucosal surfaces, manifested as gingival bleeding, epistaxis, or menorrhagia. Less commonly, widespread severe bleeding is seen in patients with disseminated intravascular coagulation (seen in acute promyelocytic leukemia and monocytic leukemia). Infection is due to neutropenia, with the risk of infection becoming high as the neutrophil count falls below 500/mL. Patients with neutrophil counts less than 100/mL almost invariably become infected within several days. The most common pathogens are gram-negative bacteria (E coli, Klebsiella, Pseudomonas) or fungi (Candida, Aspergillus). Common presentations include cellulitis, pneumonia, and perirectal infections. Septicemia in severely neutropenic patients can cause death within a few hours if treatment with appropriate antibiotics is delayed.
Patients may also seek medical attention because of gum hypertrophy and bone and joint pain. The most dramatic presentation is hyperleukocytosis, in which a markedly elevated circulating blast count (usually > 200,000/mL) leads to impaired circulation, presenting as headache, confusion, and dyspnea. Such patients require emergent leukapheresis and chemotherapy.
On examination, patients are usually pale and have purpura, petechiae, and various signs of infection. Stomatitis and gum hypertrophy may be seen in patients with monocytic leukemia. There is variable enlargement of the liver, spleen, and lymph nodes. Bone tenderness, particularly in the sternum and tibia, may be present.
B. Laboratory Findings: The hallmark of acute leukemia is the combination of pancytopenia with circulating blasts. However, blasts may be absent from the peripheral smear in as many as 10% of cases (“aleukemic leukemia”). The bone marrow is usually hypercellular and dominated by blasts. More than 30% blasts are required to make a diagnosis of acute leukemia.
A number of other laboratory abnormalities may be present. Hyperuricemia may be seen. If disseminated intravascular coagulation is present, the fibrinogen level will be reduced, the prothrombin time prolonged, and fibrin degradation products or fibrin D-dimers present. Patients with acute lymphoblastic leukemia (especially T cell) may have a mediastinal mass visible on chest radiograph. Patients with meningeal leukemia will have blasts present in the spinal fluid. This is seen in approximately 5% of cases at diagnosis and is more common in monocytic types of acute myelogenous leukemia.
Acute leukemia should be classified as either acute lymphoblastic or acute myelogenous leukemia, also called acute nonlymphocytic leukemia. Patients with acute myelogenous leukemia may have granules visible in the blast cells. The Auer rod, an eosinophilic needle-like inclusion in the cytoplasm, is pathognomonic of acute myelogenous leukemia. To confirm the myeloid nature of the cells, histochemical stains demonstrating myeloid enzymes such as peroxidase or chloroacetate esterase may be useful. Monocytic lineage can be demonstrated by the finding of butyrate esterase. Acute lymphoblastic leukemia should be considered when there is no morphologic or histochemical evidence of myeloid or monocytic lineage. The diagnosis is confirmed by demonstrating surface markers characteristic of primitive lymphoid cells. Terminal deoxynucleotidal transferase (TdT) is present in 95% of cases of acute lymphoblastic leukemia. A variety of monoclonal antibodies have been used to define other phenotypes of acute lymphoblastic leukemia. Primitive B lymphocyte antigens include CD10 and CD19. T cell acute lymphoblastic leukemia is diagnosed by the finding of CD2, CD5, and CD7.
Acute myelogenous leukemia is usually categorized on the basis of morphology and histochemistry as follows: Acute undifferentiated leukemia (M0), acute myeloblastic leukemia (M1), acute myeloblastic leukemia with differentiation (M2), acute promyelocytic leukemia (M3), acute myelomonocytic leukemia (M4), acute monoblastic leukemia (M5), erythroleukemia (M6), and megakaryoblastic leukemia (M7).
Acute lymphoblastic leukemia is most usefully classified by immunologic phenotype as follows: common, early B lineage, and T cell.
Cytogenetic studies have emerged as the most powerful prognostic factor in the acute leukemias. Favorable cytogenetics in acute myeloid leukemia include t(8;21), t(15;17), and inv(16)(p13;q22), These patients have a higher chance of achieving both short- and long-term disease control. Favorable cytogenetics in acute lymphoblastic leukemia are the hyperdiploid states. Unfavorable cytogenetics are monosomy 5 and 7, Philadelphia chromosome, and abnormalities of 11q23.