Hyperleukocytosis and Leukostasis
Hyperleukocytosis: Generally defined as total WBC count >100 X 10^9/L
Leukostasis: syndrome characterized by reduced tissue perfusion that can occur with hyperleukocytosis, but generally occurs much more commonly in AML (and CML in the adult population)
characterized by WBC plugs in the microvasculature/capillaries
Respiratory distress and neurological findings most common organs affected
Untreated, carries high mortality (up to 20-40 percent)
Leukostasis occurs more commonly in leukemias which have larger, less deformable blasts.
AML: Hyperleukocytosis in 10-20 percent of patients, leukostasis more common with WBC >100 X 10^9 cells
ALL: Hyperleukocytosis in 10-30 percent of patients, leukostasis very rare
Leukostasis is thought to occur due to increased blood viscosity (secondary to large population of blasts that are not very deformable) as well as high metabolic demands of the circulating blasts producing localized hypoxemia. In addition, production of cytokines can lead to direct endothelial damage. Cells also adhere to the vascular endothelium.
High numbers of circulating blasts leads to sludging, obstruction of capillaries and subsequent tissue malperfusion. In addition, circulating blasts induce endothelial adhesion receptor expression (ie E selectin, P selectin ICAM-1) leading to further adhesion and sludging.
CNS and respiratory manifestations are the most common
CNS signs and symptoms include: headache, dizziness, visual changes, confusion, and even coma. Patients are at risk for intracranial bleed (? reperfusion injury after cytoreduction)
Pulmonary signs and symptoms include: dyspnea, hypoxia, CXR changes consistent with alveolar infiltrates. PaO2 may be falsely decreased as a result of blast oxygen utilization and hence, pulse oximetry may be more reliable as a marker of adequacy of the pulmonary system to oxygenate the blood
Fever very common (80%) and may be secondary to the leukemia but generally empirically treated for infection
Other less common findings include myocardial injury, renal injury, bowel ischemia, and priapism
falsely decreased PaO2 due to enhanced uptake by circulating blasts
overestimated platelets (blast fragments counted as platelets occasionally)
evidence of spontaneous tumor lysis syndrome (elevated K/uric acid/phosphorous, decreased Ca)
Pathologic diagnosis with biopsy demonstrating WBC plugs in the microvascualture
Leukostasis (not necessarily hyperleukocytosis) constitutes a medical emergency and again, is associated with significant mortality
Cytoreduction is the mainstay of treatment and can be achieved with:
Chemotherapy: hydroxyurea (in those unable to receive induction chemotherapy) or induction chemotherapy
No evidence to compare the effectiveness of the two therapies
Monitoring for tumor lysis
Rasburicase generally given for uric acid >8 mg/dL
Twice maintenance fluids without potassium with goal UOP 2-3 cc/kg/hr
Leukapheresis: Role in treatment of hyperleukocytosis is controversial
Generally requires CVL or large bore peripheral IVs
May not always be effective in reducing the WBC
Can exacerbate DIC in APML
Generally avoid RBC transfusions as this can increase viscosity and exacerbate leukostasis
Similarly, avoid diuretics as this can increase viscosity
Risk of intracranial hemorrhage highest when WBC count has been greatly reduced (perhaps indicating risk of reperfusion injury) and so platelets generally maintained >20-30K
3) Porcu P, Danielson CF, Orazi A, et al. Therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation between degree of cytoreduction and early mortality rate. Br J Haematol 1997; 98:433.
4) Giles FJ, Shen Y, Kantarjian HM, et al. Leukapheresis reduces early mortality in patients with acute myeloid leukemia with high white cell counts but does not improve long- term survival. Leuk Lymphoma 2001; 42:67.
5) Thiébaut A, Thomas X, Belhabri A, et al. Impact of pre-induction therapy leukapheresis on treatment outcome in adult acute myelogenous leukemia presenting with hyperleukocytosis. Ann Hematol 2000; 79:501.