In a patient with chronic myeloid leukemia presenting with anemia and ascites, what are the likely causes and the recommended diagnostic evaluation and management?

CML with Anemia and Ascites: Causes and Management

Primary Causes of Ascites in CML

Ascites in a CML patient most commonly indicates blast phase transformation with extramedullary leukemic infiltration, though rare cases of chronic phase CML with peritoneal/mesenteric involvement have been documented. 1, 2

Blast Crisis with Leukemic Ascites

• Blast phase CML can present with leukemic ascites due to direct peritoneal infiltration or hepatic leukemic infiltration causing portal hypertension 1
• Flow cytometry analysis of peritoneal fluid will reveal myeloblasts consistent with blast crisis 1
• Hepatic infiltration appears as coarse echotexture on ultrasound and causes severely deranged liver function with coagulopathy 1
• This presentation confers extremely poor prognosis with median survival of 3-6 months 1

Chronic Phase CML with Extramedullary Disease

• Massive ascites can rarely occur during chronic phase CML from mesenteric/peritoneal infiltration 2
• This unusual presentation responds excellently to tyrosine kinase inhibitor therapy with complete resolution of ascites 2

TKI-Related Fluid Retention

• Severe fluid retention including ascites occurs in 1.3% of newly diagnosed CML patients and 2-6% of other CML patients treated with imatinib 3
• Risk increases with higher imatinib doses and age >65 years 3
• This is distinct from leukemic ascites and represents drug toxicity rather than disease progression 3

Causes of Anemia in CML

Disease-Related Anemia

• Anemia in CML typically indicates either blast phase transformation with bone marrow failure or ineffective erythropoiesis from concurrent nutritional deficiency 4, 5
• Chronic phase CML characteristically presents with preserved or elevated blood counts, not anemia 6, 7
• Cytopenias including anemia are typical of blast phase due to bone marrow replacement by blasts 6

Nutritional Deficiency Masking CML

• Vitamin B12 or folate deficiency can cause megaloblastic anemia that masks the typical leukocytosis of CML 5
• Ineffective erythropoiesis from nutritional deficiency results in anemia and thrombocytopenia despite underlying CML 5
• Following vitamin replacement, marked leukocytosis becomes evident as the megaloblastic component resolves 5

TKI-Induced Myelosuppression

• All tyrosine kinase inhibitors cause hematologic toxicity including anemia 3, 4
• Cytopenias occur more frequently in accelerated phase or blast crisis than chronic phase 3

Diagnostic Evaluation

Immediate Assessment

• Perform flow cytometry on ascitic fluid to detect myeloblasts indicating leukemic ascites 1
• Obtain abdominal ultrasound to assess for hepatic infiltration (coarse echotexture) 1
• Check liver function tests and coagulation studies, as hepatic infiltration causes severe derangement 1
• Perform bone marrow aspirate and biopsy to determine disease phase (blast percentage) 7, 1

Disease Phase Determination

• Blast phase is defined as ≥20% blasts by WHO criteria or ≥30% by MD Anderson/European LeukemiaNet criteria 4
• Chronic phase requires <10% blasts in blood/bone marrow, absence of extramedullary disease, <20% basophils, and platelets 100-1000 × 10⁹/L 4
• Quantitative RT-PCR for BCR-ABL1 transcripts establishes baseline and monitors treatment response 7, 8

Nutritional Assessment

• Check vitamin B12 and folate levels in any CML patient presenting with unexplained anemia 5
• Peripheral smear showing hypersegmented neutrophils and megalocytes suggests concurrent megaloblastic anemia 5

Management Approach

For Blast Crisis with Leukemic Ascites

• Initiate acute myeloid leukemia-type induction chemotherapy with dose modifications based on liver function 1
• Consider allogeneic hematopoietic stem cell transplant, which offers cure rates of 20-60% depending on disease stage 4
• Prognosis remains poor with median survival 3-6 months despite treatment 1

For Chronic Phase CML with Extramedullary Ascites

• Start tyrosine kinase inhibitor therapy (imatinib, dasatinib, nilotinib, bosutinib, or asciminib as first-line options) 4, 2
• Expect excellent response with complete resolution of ascites and achievement of complete cytogenetic response 2
• Monitor BCR-ABL1 transcripts every 3 months during first year 7

For TKI-Related Fluid Retention

• Weigh patients regularly and investigate unexpected rapid weight gain 3
• Reduce TKI dose or switch to alternative TKI with lower fluid retention risk 3
• Provide appropriate diuretic therapy for symptomatic fluid retention 3

For Nutritional Deficiency

• Administer vitamin B12 and folic acid replacement, which rapidly improves anemia and thrombocytopenia 5
• Anticipate emergence of leukocytosis as megaloblastic component resolves, revealing underlying CML 5
• Initiate TKI therapy once nutritional status corrected 5

Critical Pitfalls

• Do not assume ascites in CML is always cirrhotic or TKI-related; always perform diagnostic paracentesis with flow cytometry to exclude leukemic ascites 1
• Anemia in a CML patient should prompt immediate evaluation for blast crisis rather than assuming it is treatment-related 4, 1
• Hepatic infiltration with coagulopathy requires chemotherapy dose modifications to prevent life-threatening toxicity 1
• Consider comorbidities when selecting TKI, as arterio-occlusive events (nilotinib, ponatinib), pleural effusion (dasatinib), and GI disturbance (bosutinib) have agent-specific risks 4, 9