What is the best approach to manage increased lightheadedness and dizzy spells in a patient with a history of Chronic Lymphocytic Leukemia (CLL) and myeloid sarcoma?

Management of Lightheadedness and Dizzy Spells in CLL with Myeloid Sarcoma

The priority is to immediately evaluate for life-threatening causes including anemia, thrombocytopenia, infection/sepsis, CNS involvement by myeloid sarcoma, and orthostatic hypotension, as these directly impact mortality and require urgent intervention. 1, 2, 3

Immediate Assessment Required

Hematologic Evaluation

• Obtain complete blood count with differential to assess for worsening anemia or thrombocytopenia, which are common CLL complications that can cause dizziness and represent treatment indications 1, 2
• Anemia causing symptoms or thrombocytopenia warrant immediate intervention, as these indicate progressive disease requiring treatment 1
• If autoimmune cytopenias are identified (autoimmune hemolytic anemia or immune thrombocytopenia), initiate corticosteroids as first-line therapy 1, 2

Orthostatic Vital Signs

• Measure blood pressure supine and after 1-3 minutes of standing to identify orthostatic hypotension (≥15 mmHg systolic drop) 3
• Paraneoplastic autonomic neuropathy can occur with myeloid malignancies, presenting as severe orthostatic hypotension that resolves with treatment of the underlying leukemia 3
• If orthostatic hypotension is confirmed with systolic drops >15 mmHg accompanied by dizziness, consider midodrine 10 mg three times daily (last dose before 6 PM to avoid supine hypertension), which elevates standing systolic pressure by 15-30 mmHg within 1 hour 4

Infection Screening

• Evaluate for active infection including vital signs, physical examination for cellulitis or other focal infections, and consider blood cultures if febrile, as CLL patients develop severe immune defects making infections the most common complication 5, 2
• Check CMV PCR if patient has received alemtuzumab or other immunosuppressive therapy, as CMV reactivation can occur even without symptoms 1
• For confirmed infections, administer full 10-day antibiotic courses due to compromised immunity; severe cases require hospitalization for IV antibiotics 5

Neurologic Assessment

• Perform focused neurologic examination to exclude CNS involvement by myeloid sarcoma, which can cause cord compression or other neurologic deficits requiring urgent intervention 6
• Myeloid sarcoma can involve the CNS and cause progressive neurologic symptoms; MRI is indicated if focal deficits are present 6

Disease-Specific Considerations

CLL Disease Activity

• Assess for treatment indications per IWCLL criteria: progressive lymphocytosis (>50% increase over 2 months), massive lymphadenopathy (≥10 cm), massive splenomegaly (≥6 cm below costal margin), or constitutional symptoms (unintentional weight loss ≥10%, significant fatigue, fevers >100.5°F for ≥2 weeks, night sweats >1 month) 1
• Constitutional symptoms including significant fatigue (ECOG PS ≥2) represent a treatment indication and may explain the dizziness 1

Richter Transformation Evaluation

• Consider Richter transformation (2-15% of CLL patients) if there is rapid clinical deterioration, new B-symptoms, or rapidly enlarging lymph nodes, as this carries very poor prognosis and requires different management 1, 2
• PET-CT can guide lymph node biopsy if transformation is suspected; histopathologic confirmation is required 1

Treatment Decisions Based on Findings

If Anemia/Thrombocytopenia Present

• Bone marrow aspirate and biopsy are indicated for cytopenia of uncertain cause 1
• If autoimmune: corticosteroids first-line; if refractory, consider rituximab or anti-CD20 antibody-based CLL treatment 1, 2
• If disease-related: initiate CLL-directed therapy based on TP53/del(17p) status and IGHV mutation status 1

If Orthostatic Hypotension Confirmed

• Start midodrine 10 mg three times daily (avoid doses within 3-4 hours of bedtime) 4
• Monitor for supine hypertension; patients should sleep with head of bed elevated 4
• Treat underlying myeloid malignancy, as paraneoplastic autonomic dysfunction may resolve with leukemia treatment 3

If Infection Identified

• Administer appropriate antimicrobials for full 10-day course minimum 5
• Consider prophylactic antibiotics, antivirals, or antifungals for patients with recurrent infections 2
• Evaluate for IV immunoglobulin replacement if severe hypogammaglobulinemia with repeated infections 5, 2

Common Pitfalls to Avoid

• Do not attribute dizziness solely to age or deconditioning without excluding life-threatening causes including severe anemia, infection, or CNS involvement 1, 2, 3
• Do not delay treatment of underlying hematologic malignancy if paraneoplastic autonomic neuropathy is suspected, as delay can lead to irreversible neurologic deficit and increased mortality 3
• Avoid using lymphocyte count alone as treatment indication; CLL rarely causes hyperviscosity symptoms despite high counts 1
• Monitor closely for medication interactions if starting midodrine, particularly with cardiac glycosides, MAO inhibitors, or other vasoconstrictors 4