Lymphoproliferative and Myeloproliferative Disorders

By | 2012-11-10

Leukemia is the abnormal proliferation of hematopoietic cells that encompasses both lymphoproliferative and myeloproliferative disorders and is considered rarer in the horse than in other species. Leukemia can be classified based on the (1) type of abnormal cell: lymphoid or myeloid; (2) degree of tumor differentiation: acute or chronic; and (3) number of specific types of abnormal cells that are circulating in the peripheral blood: aleukemic, subleukemic, or leukemic. In addition, tumor cells can be further characterized by histochemical and immunohistologic methods. The lymphoproliferative (lymphoma, lymphoid leukemia, and plasma cell myeloma) and myeloproliferative (the myeloid leukemias and erythrocytosis) disorders of the horse are reviewed in this post.

Lymphoma

Plasma Cell Myeloma

Plasma cells are terminally differentiated B cell lymphocytes. Malignant transformation can result in three categories of tumors: chronic B cell lymphocytic leukemia, B cell lymphoma (considered above), and plasma cell tumors. Plasma cell tumors occur rarely in the horse; most of the reported information is derived from individual cases and a retrospective series of 10 cases (). No risk factors have been established, and affected animals have ranged from 3 months to 22 years of age. Solitary plasmacytoma is the term used for a single extramedullary tumor. However, the most common form of plasma cell tumors in horses involves the bone marrow and is called multiple myeloma.

Plasma Cell Myeloma: Clinical Signs

Clinical signs are associated with the sites of tumor invasion and include limb edema, ataxia, lameness, epistaxis, lymphadenopathy, weight loss, and anorexia. Secondary infections that commonly involve the lower respiratory or urinary tract may develop. Anemia and hyperglobulinemia are the most common abnormal laboratory findings. With myelophthisic disease, the anemia may be severe and accompanied by leukopenia and thrombocytopenia. Hypoalbuminemia may accompany hyperglobulinemia. A monoclonal gammopathy is detected in nearly all cases by serum electrophoresis and reflects the malignant transformation and clonal expansion of a single plasma cell lineage. The monoclonal protein, called a paraprotein, may be a complete or partial immunoglobulin, the majority of which are in the IgG class. Analysis of urine may reveal proteinuria, and the heat-precipitation method has confirmed the presence of light chains (Bence Jones protein) in the urine of a few horses. Occasionally, hypercalcemia may be found as a paraneoplastic condition.

Diagnosis of Plasma Cell Myeloma

In human patients, definitive diagnosis is based on the demonstration of bone marrow plasmacytosis (>10% of cells) or an extramedullary plasmacytoma and one of the following: (1) a serum monoclonal gammopathy; (2) detection of a urine monoclonal protein; or (3) osteolytic lesions. The majority of equine cases have a monoclonal gammopathy; however, cases in which the serum globulin content was within normal limits have been described. Further examinations should include skeletal survey radiographs of the long bones and cervical vertebrae and biochemical tests to detect renal or hepatic involvement.

Prognosis and Treatment of Plasma Cell Myeloma

Most horses die or are euthanized within 4 months of developing clinical signs, but longer survival times have been reported in a few horses treated with antineoplastic agents. Melphalan (Alkeran), prednisone, and cyclophosphamide have been used in the treatment of multiple myeloma in an 18-year-old Quarter Horse mare. Diagnosis was confirmed 1 week before foaling. Chemotherapy was started after the foal was weaned at 4 days of age; however, dosages were not reported, and plasmapheresis was also performed. The mare was euthanized 7 months after diagnosis because of severe chronic laminitis. A 20-year-old horse with multiple myeloma was also treated with melphalan (7 mg/mz PO q24h for 5 days, and then every 3 weeks). The horse’s condition remained stable for 1 year after diagnosis.

Myeloid Leukemias

Myeloproliferative disorders are characterized by medullary and extramedullary proliferation of bone marrow constituents, including the erythroid, granulocytic, monocytic, and megakaryocytic cell series. Myelodysplastic syndromes are characterized by refractory cytopenia, which generally progresses to acute myeloid leukemia. Classification schemes for myeloid leukemia are based on the degree of differentiation of the transformed cell line. For example, chronic myeloid leukemia involves neutrophils and late precursor cells, whereas acute myeloid leukemia involves myeloblast cells. In general, chronic leukemias are less aggressive than acute leukemias. Reports of myeloproliferative disorders of horses are rare and are dominated by acute leukemias of the granulocytic cell series.

Clinical Signs of Myeloid Leukemias

In a review of 11 reported cases of myelogenous leukemia in the horse, the ages ranged from 10 months to 16 years, and both genders and various breeds were affected. Common clinical findings included ventral and peripheral edema, petechiae, weight loss, depression, and enlarged lymph nodes. Less common findings were fever, epistaxis, pneumonia, exercise intolerance, and colic. All were found to be anemic and thrombocytopenic and had circulating neoplastic cells; the majority had neutropenia and a gammopathy. Secondary infections seem more common in this form of hematopoietic disorders, presumably as a result of immunosuppression. Two horses with myelomonocytic leukemia developed pulmonary aspergillosis.

Diagnosis of Myeloid Leukemias

Bone marrow examination confirms the diagnosis. Confirmation of cell lineage may be morphologically obvious. When needed, further characterization is possible with histochemical and immunohistologic or flow cytometric identification of cell-surface antigens or enzyme content.

Myeloid Leukemias: Prognosis and Therapy

Myelogenous leukemias are notoriously resistant to common antineoplastic agents. However, chemotherapy has been attempted in at least two cases of equine acute myelomonocytic leukemia. These horses were given cytosine arabinoside, based on a low-dose protocol (10 mg/m2 q12h for 3 weeks) adopted from human cancer medicine. The aim of this therapy is to promote terminal differentiation of the neoplastic cell line and diminish clonal expansion. Newer modalities are being tested in human patients and include the use of hematopoietic cytokines and bone marrow transplantation, but no reports of similar use in equine cancer patients exist.