Overview

• Lymphoproliferative disorder defined as the proliferation of neoplastic prolymphocytes and lymphoblasts in the bone marrow; most are of B-cell origin.
• Leads to displacement and/or depression of normal hematopoietic cells (myelophthisis).
• Neoplastic lymphoblasts are usually, but not always, circulating in the blood.
• May infiltrate other organs including spleen, liver, and lymph nodes.

Signalment

• Dog-no significant sex predilection; with a mean age in one report 7.4 years old (range, 2–12 years), preponderance of large- and giant-breed dogs.
• Rare in cat (also younger animals, especially with FeLV infection).

Signs

• Often nonspecific, can include anorexia, weight loss, and lethargy.
• Hepatosplenomegaly.
• Mild to moderate lymphadenomegaly.
• Petechial or ecchymotic hemorrhages.

Causes & Risk Factors

• Dogs-genetic factors, ionizing radiation, oncogenic viruses, and chemical agents including alkylating chemotherapy drugs are suspected, but unproven; missense mutations and tandem duplications have been identified in oncogenes such as Flt3, c-kit, and N-ras in dogs with ALL.
• Cats-FeLV infection.

Differential Diagnosis

• Acute or chronic infection-toxoplasmosis; canine distemper; ehrlichiosis.
• Aplastic anemia.
• Metastatic neoplasia.
• Multicentric lymphoma with bone marrow involvement and circulating lymphoblasts can be difficult to distinguish from ALL. Lymphoma is typically characterized by bulky peripheral disease and minor bone marrow and peripheral blood involvement, whereas ALL has significant bone marrow and peripheral blood involvement and mild to moderate lymphadenopathy.
• Other leukemias and myeloproliferative disorders.

CBC/Biochemistry/Urinalysis

• CBC-normocytic, normochromic, nonregenerative anemia (98%); neutropenia (78%); thrombocytopenia (90%); all present in >75% of cases.
• CBC may also show lymphoblastic lymphocytosis, leukopenia, or both.
• Serum chemistry profile-elevated liver enzyme activities.

Other Laboratory Tests

• Careful bone marrow cytopatholgoy-expansion of neoplastic lymphoblasts (>30%) is the hallmark. Can also see low numbers of myeloid/erythroid precursors and megakaryocytes depending on extent of bone marrow involvement, cell type of origin, and differentiation.
• Bone marrow core biopsy with immunohistochemical or enzymatic biochemical studies can be helpful if bone marrow cannot be obtained.
  • Enzymes include peroxidase and chloroacetate ester.
  • Flow cytometry using monoclonal antibodies against cell surface antigens on bone marrow aspirates and/or blood is typically used to characterize disease.
  • Useful antibodies include CD45 (all hematopoietic cells beside erythrocytes), CD34 (progenitor cells), CD18 (leukocytes), CD79a (B cells), and CD3 (T cells).
  • The majority of ALL cells are CD34+, while the majority of lymphoma cells are CD34-.
• PCR for antigen receptor rearrangements (PARR) can confirm a clonally expanded population if bone marrow cytology and/or flow cytometry results are equivocal.

Imaging

Radiography and ultrasonography often reveal hepatomegaly and splenomegaly.

Diagnostic Procedures

Bone marrow aspirate and biopsy

Drug(s)

• L-asparaginase (400 IU/kg IM/SC after pre-treating with diphenhydramine); usually used as initial induction agent.
• Combination chemotherapy-prednisone (20–30 mg/m² PO q12h), vincristine (0.5–0.7 mg/m² IV weekly), and cyclophosphamide (200–250 mg/m² divided PO weekly); may result in partial or short-lived complete remission.
• Cytosine arabinoside (400–600 mg/m² IV weekly); administer as constant rate infusion over 6–8 hours, can cause thrombocytopenia or other myelosuppression.
• More aggressive chemotherapeutic agents may be used after lymphocytosis has lessened and cytopenias have resolved.

Contraindications/Possible Interactions

Acute tumor lysis syndrome (life-threatening bradycardia secondary to an acute increase in serum potassium and phosphorus levels following induction chemotherapy) can be seen in ALL dogs with high neoplastic cell counts. Consider high-rate fluid diuresis or peripheral blood leukoreduction using an apheresis machine.

Patient Monitoring

Monitor peripheral blood count and bone marrow-judge success and toxicity of treatment.

Possible Complications

Hemorrhage from thrombocytopenia-major cause of death in dogs.

Expected Course and Prognosis

Most dogs will have a short-lived complete or partial remission with induction chemotherapy. Prognosis is grave with most dogs succumbing to resistant disease within a few weeks to months.

Pregnancy/Fertility/Breeding

Chemotherapy-contraindicated in pregnant animals

Abbreviations

• ALL = acute lymphoblastic leukemia
• FeLV = feline leukemia virus
• PCR = polymerase chain reaction
• RBC = red blood cell