What is an important pulmonary sequela to consider in patients with Chronic Myeloid Leukemia (CML)?

Important Pulmonary Sequelae of CML

The most important pulmonary sequelae to consider in CML patients are pleural effusion (particularly with dasatinib therapy), pulmonary arterial hypertension (PAH) associated with dasatinib, and pulmonary leukostasis during blast crisis. 1

TKI-Associated Pulmonary Complications

Pleural Effusion

Pleural effusion is the most clinically significant pulmonary complication in CML, with dramatically different incidence rates depending on the TKI used:

• Dasatinib carries the highest risk, with 28% incidence at 5 years in first-line therapy compared to only 1% with imatinib 1
• The risk does not decrease with time and recurrence occurs in approximately 70% of cases after dasatinib withdrawal 1
• Grade 3/4 pleural effusions occur in 4% of dasatinib-treated patients 1
• Risk factors include: pre-existing lung disorders, uncontrolled hypertension, prior cardiac history, and twice-daily dosing schedules 1

Clinical presentation includes significant dry cough, fatigue, chest pain, and dyspnea 1

Management approach:

• Dasatinib should be avoided in patients with existing lung disorders or uncontrolled hypertension 1
• Close monitoring and timely intervention are essential for continuing dasatinib treatment 1
• Withdrawal of dasatinib may totally or partially reverse the effusion, though pharmacologic treatment may be needed 1

Pulmonary Arterial Hypertension (PAH)

PAH is a rare but serious complication specifically associated with dasatinib:

• Patients with pre-existing PAH should be considered for alternative TKIs in the front-line setting 1
• Withdrawal of dasatinib may reverse PAH, though pharmacologic treatment may be required 1
• Patients with pre-existing PAH conditions should be monitored closely if dasatinib is used 1

Pneumonitis

Pneumonitis is a rare complication, most commonly associated with imatinib:

• Detected in 4% of patients by 2 years 1
• Both hypersensitivity and eosinophilic types have been described 1
• Treatment requires: discontinuation of the medication and administration of glucocorticoids 1
• Switching to nilotinib or bosutinib are preferred options if pneumonitis is not mild 1

Disease-Related Pulmonary Complications

Pulmonary Leukostasis

Pulmonary leukostasis is a life-threatening emergency that occurs primarily during blast crisis:

• Characterized by increasing dyspnea, hypoxemia, fever, and impending respiratory failure 2
• Can occur even without extreme hyperleukocytosis (WBC <50,000/mm³), as circulating blasts and endothelial affinity are more important factors than absolute WBC count 3
• Emergency management includes: aggressive leukapheresis and cytoreduction 4
• Single-agent imatinib mesylate has been reported effective for rapid WBC reduction in blast crisis with pulmonary leukostasis, avoiding tumor lysis syndrome risk 2

Fluid Retention and Pulmonary Edema

Severe fluid retention including pulmonary edema occurs with all TKIs:

• Reported in 1.3% of newly diagnosed CML patients and 2-6% of other adult CML patients 5
• Probability increases with higher imatinib doses and age >65 years 5
• Regular weight monitoring and investigation of unexpected rapid weight gain are essential 5

Clinical Monitoring Recommendations

Baseline assessment before TKI initiation should identify:

• Pre-existing lung disorders (contraindication to dasatinib) 1
• Uncontrolled hypertension (increased pleural effusion risk with dasatinib) 1
• Pre-existing PAH (consider alternative to dasatinib) 1
• Cardiac disease or risk factors (increased fluid retention risk) 5

Ongoing surveillance should include:

• Regular assessment for respiratory symptoms (cough, dyspnea, chest pain) 1
• Weight monitoring for fluid retention 5
• Prompt evaluation of acute respiratory symptoms, particularly in blast crisis 2, 3