Overview

• Uncommon, lymphoproliferative disorder.
• Slowly progressive over months to years.
• Circulating neoplastic lymphocytes are mature and well differentiated.
• May originate in spleen or bone marrow.

Systems Affected

• Hematopoietic
• Lymphatic

Signalment

• More frequent in dog than cat.
• Dogs-mean age, 10 years (range, 1.5–15 years); male-to-female ratio approaches 2:1.
• Cats-median age 12.5 years (range, 5–20); male-to-female ratio 2:1.

Signs

• Nonspecific, often no clinical signs of illness
• Lethargy, decreased appetite, chronic weight loss
• Lymphadenomegaly, splenomegaly
• Fever
• Polydipsia and polyuria

Causes & Risk Factors

Unknown

Differential Diagnosis

• Lymphoma-may have a leukemic phase (stage V).
• Acute lymphoblastic leukemia.
• Immune-mediated hematologic diseases.
• Chronic antigenic stimulation (reactive lymphocytosis)-ehrlichiosis, leptospirosis, leishmaniasis.
• Acute viral infection associated lymphocytosis.

CBC/Biochemistry/Urinalysis

• Lymphocytosis-range, 5,000–>500,000 cells/µL, typically small, mature lymphocytes.
• In dogs, more than 60% have large granular lymphocyte (LGL) morphology.
• Larger cells may be observed, especially with progression to blast crisis (advanced stage).
• Mild-to-moderate normocytic, normochromic anemia (nonregenerative).
• Normal-to-low platelet count (less than 20% cases).
• Normal-to-mildly increased serum globulins.

Other Laboratory Tests

• Cytologic examination (bone marrow aspirate or core biopsy)-may show high numbers of mature lymphocytes (especially B-cell CLL); crowding out of normal cell lines in advanced stages.
• Immunocytochemistry, flow cytometry, PCR for antigen receptor rearrangement (PARR) to determine cell lineage.
• If hyperglobulinemia, serum protein electrophoresis to detect monoclonal gammopathy.
• Direct Coombs' test-may be positive with secondary immune-mediated hemolytic anemia.
• Serology for E. canis.

Imaging

Radiography and ultrasonography may reveal splenomegaly or internal lymphadenomegaly.

Diagnostic Procedures

• Bone marrow aspiration (cytology) or biopsy (histopathology).
• Lymph node and spleen cytology or histopathology.

Drug(s)

• Chlorambucil 6 mg/m² PO q24h for 7–14 days; then 6 mg/m² PO q48h and eventually (maintenance) 2–4 mg/m² q48h, adjusted based on response and CBC (dogs); 2 mg q2–4 days (cats).
• Prednisone 40 mg/m² PO q12h (dogs); 5–10 mg/cat q24h (cats; use prednisolone); in combination with chlorambucil; may be tapered or discontinued when lymphocyte count normalizes.
• Alternative chemotherapy agents and protocols to be considered when resistance or blast crisis develops over time, consult with an oncologist.

Contraindications/Possible Interactions

Chemotherapy may have toxic side effects; seek advice with oncologist before starting treatment if you are unfamiliar with cytotoxic drugs.

Patient Monitoring

Initially, biweekly examination of CBC-response to treatment and disease progression.

Possible Complications

Chronic chemotherapy-induced myelosuppression; may need to alter dosage, depending on neutrophil and platelet counts.

Expected Course and Prognosis

• Variable course, but eventually progressive to blast crisis or becomes resistant to therapy.
• Median survival time with therapy approaches 18 months in dogs with B-cell CLL, and surpasses 24 months in dogs with T-cell CLL.
• Median survival time with therapy in cats was >14 months in one study.

Pregnancy/Fertility/Breeding

Chemotherapy contraindicated in gestating animals

Abbreviations

• CLL = chronic lymphocytic leukemia
• LGL = large granular lymphocyte
• PCR = polymerase chain reaction