In a patient with chronic myeloid leukemia (CML) who develops ascites, how should I evaluate and manage it?

Ascites in CML: Evaluation and Management

Ascites in a CML patient is rare and demands immediate investigation to distinguish between disease progression (extramedullary blast crisis), TKI-related fluid retention, or alternative causes—with management hinging on identifying the underlying etiology through diagnostic paracentesis and disease phase assessment.

Initial Diagnostic Approach

Determine Disease Phase First

• Assess for disease progression to accelerated or blast phase, as extramedullary involvement with ascites typically occurs during transformation and carries grave prognostic implications 1, 2.
• Obtain peripheral blood blast count and bone marrow examination to evaluate blast percentage, as ≥15% blasts defines accelerated phase and ≥30% defines blast crisis 1.
• Perform bone marrow cytogenetics to identify additional chromosomal abnormalities (+8, iso(17q), +19, +22q-, chromosome 3 aberrations) that indicate higher risk of progression 3.

Perform Diagnostic Paracentesis

• Obtain ascitic fluid for cell count with differential, cytology, albumin, total protein, and flow cytometry to distinguish between portal hypertension, peritoneal carcinomatosis, and leukemic ascites 4.
• Calculate serum-ascites albumin gradient (SAAG): high gradients (≥1.1 g/dL) suggest portal hypertension, while low gradients (<1.1 g/dL) may indicate infection or malignant involvement 4.
• Flow cytometry analysis of peritoneal fluid can reveal myeloblasts consistent with leukemic ascites in blast crisis 2.

Evaluate for TKI-Related Causes

• Review current TKI therapy and recent surgical history, as imatinib can cause isolated ascites, particularly after abdominal surgery due to PDGFR inhibition increasing capillary permeability 5.
• Consider that fluid retention is a common adverse effect of imatinib but rarely presents as isolated ascites without peripheral edema 5.

Management Based on Etiology

If Blast Crisis with Leukemic Ascites

• Initiate blast crisis-directed therapy immediately, as median survival is 3-6 months without treatment 2.
• Consider acute leukemia-type induction chemotherapy with dose modifications if hepatic infiltration is present 2.
• Evaluate for allogeneic stem cell transplantation, which remains an important therapeutic option for all patients in advanced phase disease 6.
• Perform BCR::ABL1 mutation testing to guide TKI selection, particularly checking for T315I mutation that requires ponatinib, asciminib, or olverembatinib 6.

If Chronic Phase with Extramedullary Disease

• Initiate or optimize TKI therapy, as chronic phase CML with extramedullary involvement (including peritoneal infiltration) can respond excellently to imatinib with complete cytogenetic response and total disappearance of ascites 7.
• Monitor BCR-ABL transcript levels every 3 months and bone marrow cytogenetics at 6 and 12 months to assess treatment response 3.

If TKI-Related Ascites

• Discontinue the offending TKI temporarily if ascites is refractory to diuretics and temporally related to drug initiation or recent surgery 5.
• Consider perioperative interruption of TKI therapy in patients requiring abdominal surgery to prevent postoperative ascites 5.
• If ascites resolves with drug discontinuation, attempt reintroduction at lower dose or switch to alternative TKI with different side effect profile 5.

If Portal Hypertension or Alternative Cause

• Restrict sodium intake to 2 g per day as initial management 4.
• Initiate diuretic therapy with spironolactone as first-line agent, potentially combined with furosemide in selected patients 4.
• If diuretic-resistant, consider large-volume paracentesis, transjugular intrahepatic portosystemic shunting, or liver transplantation depending on underlying liver disease 4.

Critical Monitoring and Pitfalls

Warning Signs Requiring Urgent Action

• Do not delay bone marrow evaluation when symptoms suggest disease progression, as blast crisis progresses rapidly and requires immediate intervention 3.
• Monitor for persistent fever, increasing fatigue, bone pain, unexplained weight loss, rapid spleen enlargement, or new lymphadenopathy as indicators of disease acceleration 3.
• Increasing blast percentage or worsening constitutional symptoms mandate immediate reassessment of disease phase 1.

Hepatic Considerations

• Assess liver function and imaging for hepatic infiltration, which can cause coagulopathy and necessitate chemotherapy dose modifications 2.
• Ultrasound showing coarse echotexture of liver suggests leukemic infiltration and portends challenging cytotoxic treatment management 2.

Treatment Response Monitoring

• Failure to achieve complete hematologic response at 3 months, minimal cytogenetic response at 6 months, or major cytogenetic response at 12 months indicates inadequate response requiring mutation testing and treatment modification 3.