Hyperleukocytosis and Leukostasis

Definition

• 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)

Pathophysiology

• 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.

Diganosis

• 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

• Lab findings:

  • falsely decreased PaO2 due to enhanced uptake by circulating blasts

  • overestimated platelets (blast fragments counted as platelets occasionally)

  • DIC

  • evidence of spontaneous tumor lysis syndrome (elevated K/uric acid/phosphorous, decreased Ca)

• Pathologic diagnosis with biopsy demonstrating WBC plugs in the microvascualture

Treatment

• 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

  • Leukapheresis

  • 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

  • University of Michigan Pediatric Hematology/Oncology Tumor Lysis Guidelines

• 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

• General concepts:

  • 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

References

1) Porcu P, Cripe LD, Ng EW, et al. Hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management. Leuk Lymphoma 2000; 39:1.

2) Lichtman MA, Rowe JM. Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations. Blood 1982; 60:279.

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.

6) Christoph Röllig, Gerhard Ehninger; How I treat hyperleukocytosis in acute myeloid leukemia. Blood 2015; 125 (21): 3246–3252. doi: https://doi.org/10.1182/blood-2014-10-551507