Leukostasis and hyperleukocytosis

Background

• Hyperleukocytosis: WBC >100,000/μL (some define as >50,000)
• Leukostasis: Symptomatic hyperleukocytosis — a hematologic emergency
  • White cell plugs obstruct microvasculature → end-organ damage
  • Most commonly seen with AML or CML in blast crisis (blast cells are larger and stickier than mature WBCs)
  • Brain and lungs are most commonly affected organs
• 20-40% of patients with leukostasis die within first week of presentation
• Key distinction: WBC count alone does not predict leukostasis — CLL patients may have WBC >200K without leukostasis because mature lymphocytes are small and deformable

Clinical Features

• Fever — present in ~80%; may be from leukostasis-related inflammation or concurrent infection
• CNS leukostasis: headache, dizziness, tinnitus, visual disturbances, confusion, ataxia, stupor, coma, intracranial hemorrhage
• Pulmonary leukostasis: Respiratory distress, hypoxemia, respiratory failure
  • Pearl: ABG may show falsely decreased PaO2 (leukocytes consume O2 in vitro); pulse oximetry is more accurate
• Other: Priapism, renal insufficiency, limb ischemia, DIC

Differential Diagnosis

Oncologic Emergencies

Related to Local Tumor Effects

• Malignant airway obstruction
• Bone metastases and pathologic fractures
• Malignant spinal cord compression
• Malignant Pericardial Effusion and Tamponade
• Superior vena cava syndrome

Related to Biochemical Derangement

• Hypercalcemia of malignancy
• Hyponatremia due to SIADH
• Adrenal insufficiency
• Tumor lysis syndrome
• Carcinoid syndrome

Related to Hematologic Derangement

• Neutropenic fever
  • Neutropenic enterocolitis (typhlitis)
• Leukostasis and hyperleukocytosis
• Hyperviscosity syndrome
• Thromboembolism

Related to Therapy

• Chemotherapy-induced nausea and vomiting
• Cytokine release syndrome
• Chemotherapeutic drug extravasation
• Differentiation syndrome (retinoic acid syndrome) in APML
• Stem cell transplant complications
• Catheter-related complications
  • Tunnel infection
  • Exit site infection
  • CVC obstruction (intraluminal or catheter tip thrombosis)
  • Catheter-related venous thrombosis
  • Fracture of catheter lumen
  • Oncologic therapy related adverse events

Evaluation

• CBC with differential and peripheral smear
• DIC labs: PT/INR, PTT, fibrinogen, D-dimer, FDP (DIC in up to 40%)
• Tumor lysis syndrome labs: BMP (potassium, calcium, phosphate), uric acid, LDH (TLS in up to 10%)
• CXR: interstitial or alveolar infiltrates
• CT head if CNS symptoms (hemorrhage or infarction)
• Blood and urine cultures if febrile
• Avoid transfusing RBCs before cytoreduction — may worsen viscosity and leukostasis symptoms

Management

• Hyperleukocytosis (asymptomatic): Hydroxyurea for cytoreduction may suffice
• Leukostasis (symptomatic):
  • Aggressive IV hydration — prevent dehydration which worsens viscosity
  • Chemotherapy — only treatment proven to improve survival; hematology consult immediately
  • Hydroxyurea 50-100 mg/kg/day for urgent cytoreduction while awaiting chemotherapy
  • Leukapheresis — temporizing measure to rapidly reduce WBC count; use if chemotherapy will be delayed
• TLS prophylaxis: Allopurinol or rasburicase, aggressive IV hydration
• Broad-spectrum antibiotics — leading cause of death in blast crisis is infection (patients are functionally neutropenic)
• Do NOT transfuse RBCs to Hgb >10 until WBC is reduced (increases viscosity)

Disposition

• Admit to ICU for symptomatic leukostasis
• Immediate hematology/oncology consult for all cases

See Also

• Tumor lysis syndrome
• Neutropenic fever
• DIC