Hyperleukocytosis is a life-threatening phenomenon that occurs when a peripheral leukocyte count exceeds 100,000/mL. An increase in the absolute number of one or more of the white blood cells is generically referred to as leukocytosis. This can be further differentiated by the breakdown of each cell lineage. Leukocytosis can be caused by normal inflammatory and immunologic responses, autoimmune diseases, myeloproliferative disorders, and hematopoietic malignancies. Elevated white blood cell counts can be seen in septicemia and leukemoid reactions, particularly those caused by Staphylococcus aureus, Haemophilus influenzae type b, Neisseria meningitidis, and Salmonella organisms (Pizzo & Poplack, 2002). Evaluation of the peripheral smear can help determine whether these cells represent acute leukemia (blasts), chronic leukemia (myeloid lineage cells in all phases of differentiation; may include early blasts), or a leukemoid reaction (Hastings, 2002). This chapter focuses specifically on leukocytosis in childhood leukemia.

The presence of excessive white blood cells in the circulation increases the viscosity of the blood and is associated with aggregation of leukemic cells in the microcirculation. The viscosity depends on the packed erythrocyte and packed lymphoblast volumes. A myeloblast is relatively large (350 to 450 mm³), whereas a lymphoblast is relatively small (250 to 349 mm³) (Pizzo & Poplack, 2002). Blast cells do not change shape readily, and they tend to trap plasma between them. This results in poor perfusion and anaerobic metabolism of blasts in the circulation, leading to accumulation of these cells, which contributes to lactic acidosis (Pizzo & Poplack, 2002). A packed cell volume of leukocytes that exceeds 20% to 35% increases the bulk viscosity of blood (Pizzo & Poplack, 2002; Nathan & Orkin, 1998). The effects of trapped plasma and high leukocyte counts become apparent in the microcirculation at lower volumes of packed cells.

A hematologic emergency is described as an acute, life-threatening event that occurs either directly or indirectly because of alterations in total white blood cells, red blood cell volume, platelets, and/or coagulation factors (Baggott et al., 2002). These events occur as a secondary result of chemotherapy, bone marrow replacement with cancerous cells, or marrow aplasia. Hyperleukocytosis is considered a hematologic emergency and requires immediate attention.

A number of events can occur as a consequence of a high white blood cell count. Hyperleukocytosis increases blood viscosity as the number of leukocytes increases. An excessive number of white blood cells may obstruct the microcirculation, causing damage to vessel walls. Severe metabolic disturbances may occur when cytotoxic therapy is initiated as a result of rapid destruction of white blood cells (Baggott et al., 2002).

Obstruction of a blood vessel can lead to intracranial or pulmonary hemorrhage, renal failure, disseminated intravascular coagulation (DIC) and, with chemotherapy, acute tumor lysis syndrome (ATLS) (Wilson et al., 2002). Hemorrhage and leukostasis are more prevalent in acute nonlymphocytic leukemia (ANLL), because the myeloblasts are larger than the lymphoblasts and therefore more easily trapped in circulation. This medical emergency occurs when clumps of leukemic blasts accumulate in the small circulatory vessels, leading to hypoxia, infarction, and hemorrhage. At very high white blood cell counts, leukemic aggregates proliferate into the cerebral vasculature and into the brain itself, leading to damage to blood vessels and hemorrhage (Pizzo & Poplack, 2002). CNS involvement may cause confusion, headache, somnolence, coma, and stroke.

Another phenomenon seen with hyperleukocytosis is pulmonary leukostasis or hemorrhage. This occurs when degenerating aggregates of leukemic blasts in the vessels and then the interstitium release their intracellular contents, damaging the alveoli. Leukemia-associated respiratory failure is exacerbated by possible toxins released from the blast cells, which damage the pulmonary endothelium and cause pulmonary hemorrhage (Pizzo & Poplack, 2002). Lung involvement can result in significant tachypnea and eventually lead to respiratory failure (Pizzo & Poplack, 2002).

Patients presenting with hyperleukocytosis are also at increased risk of cerebrovascular accidents (CVAs) and DIC. Leukemic promyelocytes enhance thrombin activation and express high levels of annexin II, which increases production of plasmin, a fibrolytic protein, causing DIC and CVA (Pizzo & Poplack, 2002) (see Chapter 11). Metabolic alterations occur as a result of the hypermetabolic state produced as the leukocytes cause pseudohypoglycemia and pseudohyperkalemia.

Tumor lysis syndrome results when massive lysis of tumor cells occurs after initiation of chemotherapy. Tumor lysis syndrome is seen almost exclusively in acute lymphocytic leukemia (ALL), because lymphoblasts are more sensitive then myeloblasts to chemotherapy (Lanzkowsky, 1995). The cause seems to arise from the release of large amounts of phosphate from lysed blasts; the phosphate co-precipitates with calcium in the kidneys, leading to hypocalcemia and sometimes renal failure. Hyperphosphatemia and secondary hypocalcemia could potentially lead to a seizure. Hyperuricemia may occur as a result of metabolism of the excess amounts of nucleic acid released. This may complicate the situation even more by impairing the body’s ability to excrete other metabolites. Hyperkalemia may cause alterations in the echocardiogram, such as an increase in T-wave amplitude, arrhythmias, and possibly cardiac arrest.

Lactic acidosis has been a metabolic accompaniment of the leukemia. The mechanism is unclear, but this condition is thought to be related to anaerobic metabolism by the leukemic cells at sites of leukostasis (Flombaum, 2000; Lester et al., 1985). Hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia may be mild to severe, depending on the leukemic burden and the rate of leukemic cell turnover (see Chapter 48).

Hyperleukocytosis occurs in approximately 9% to 13% of children with acute lymphoblastic leukemia, in 5% to 20% of children with acute nonlymphoblastic leukemia, and in virtually all children with chronic myelogenous leukemia (CML) (Altman, 2004). It is more common in infant ALL, acute myeloid leukemia (AML), T-cell ALL with a mediastinal mass, and hypodiploid ALL (Pizzo & Poplack, 2002).

Hyperleukocytosis is associated with a 23% mortality rate in ANLL and a 5% mortality rate in ALL (Lanzkowsky, 1995). Hyperleukocytosis can lead to death by CNS hemorrhage or thrombosis, metabolic complications of tumor lysis syndrome, and pulmonary leukostasis. An increase in the white blood cell count greater than 250,000/mL³ increases the risk of intracranial bleeding and death (Basade et al., 1995).

The following nursing care is prioritized.