What are the clinical manifestations of leukostasis in acute myeloid leukemia (AML) with extremely elevated white blood cell counts?

Clinical Manifestations of Leukostasis in Acute Myeloid Leukemia with Extremely Elevated White Blood Cell Counts

Leukostasis is a life-threatening emergency in AML patients with hyperleukocytosis (WBC >100 × 10⁹/L) requiring immediate cytoreductive therapy to prevent early mortality. 1, 2

Definition and Pathophysiology

• Hyperleukocytosis: White blood cell count >50-100 × 10⁹/L in AML
• Leukostasis: Clinical syndrome resulting from sludging of leukemic blasts in microvasculature
• Most common in AML due to the high adhesiveness of myeloblasts to vascular endothelium 3
• Particularly associated with FLT3 mutations 4

Clinical Manifestations by Organ System

Neurological Manifestations

• Headache, confusion, somnolence
• Altered mental status, delirium
• Visual disturbances
• Ataxia
• Cranial nerve palsies
• Seizures
• Intracranial hemorrhage
• Coma 2, 3

Pulmonary Manifestations

• Dyspnea, tachypnea
• Hypoxemia
• Diffuse alveolar hemorrhage
• Respiratory failure
• Pulmonary infiltrates on imaging
• ARDS (Acute Respiratory Distress Syndrome) 2, 3, 4

Cardiovascular Manifestations

• Myocardial ischemia
• Heart failure due to increased blood viscosity
• Hypotension
• Cardiac arrest in severe cases 3

Renal Manifestations

• Tumor lysis syndrome (hyperuricemia, hyperkalemia, hyperphosphatemia)
• Acute kidney injury
• Renal failure 2, 5

Hematological Manifestations

• Disseminated intravascular coagulation (DIC)
• Bleeding complications
• Thrombosis 2, 5

Other Manifestations

• Priapism (in male patients)
• Retinal hemorrhages and visual impairment
• Bowel infarction
• Peripheral vascular insufficiency 1, 2

Diagnostic Findings

Laboratory Findings

• WBC count typically >100 × 10⁹/L
• Elevated LDH
• Abnormal coagulation parameters (prolonged PT/PTT, decreased fibrinogen)
• Elevated D-dimer
• Thrombocytopenia
• Electrolyte abnormalities consistent with tumor lysis syndrome 2, 3

Imaging Findings

• Chest radiography: Diffuse interstitial or alveolar infiltrates
• CT brain: Intracranial hemorrhage, hypodensities suggesting infarction
• CT chest: Ground-glass opacities, interstitial thickening 3, 4

Risk Factors for Developing Leukostasis

• WBC count >100 × 10⁹/L
• AML with monocytic differentiation
• FLT3 mutations
• Younger age
• De novo AML (vs. secondary AML) 3, 4

Management Considerations

• Immediate cytoreduction is critical to prevent early mortality
• Hydroxyurea (25-60 mg/kg/day) for initial cytoreduction
• Intravenous hydration (2.5-3 liters/m²/day)
• Leukapheresis may be considered in non-APL AML with severe symptoms
• Avoid leukapheresis in APL due to risk of exacerbating coagulopathy
• Definitive chemotherapy should be initiated promptly after initial stabilization 1, 2

Prognosis

• Leukostasis is associated with high early mortality (within first week)
• Poor long-term prognosis even if initial management is successful
• Early recognition and intervention are essential to improve outcomes 3, 6

Recognizing the signs and symptoms of leukostasis early is critical as this condition represents a true hematologic emergency requiring immediate intervention to prevent fatal outcomes.