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Lymphoid Leukemia

Description - Lymphoid leukemia results from an overabundance of neoplastic white blood cells (lymphocytes) into the peripheral blood. These lymphocytes generally develop from the bone marrow but sometimes they develop in the spleen as well. Lymphocytic leukemia is more frequent than non-lymphocytic and other myeloproliferative diseases (A group of usually neoplastic diseases that are related histogenetically. These are granulocytic leukemias, myelomonocytic leukemias, polycythemia vera and myelofibroerythroleukemia).

There are mainly 2 types of lymphoid leukemia - acute lymphoid leukemia and chronic lymphoid leukemia. By ‘chronic’ we mean the disease has been continuing over a protracted period of time and by ‘acute’ we mean the disease has developed suddenly.

Acute lymphoid leukemia is highly proliferative in nature. It originates in the bone marrow and metastasizes to spleen, liver, bloodstream, nervous system, bone, lymph nodes and the gastrointestinal tract. Chronic lymphoid leukemia impairs the bone marrow and results in the under production of other blood cells that are required for combating inflammations, allergies and infections. Although elevation of lymphocytes is the most important indicator for lymphoid leukemia, the low number of white blood cells in the initial stages makes the diagnostic process extremely difficult. The clinical signs may include anemia, thrombocytopenia (relatively few platelets in blood) and neutropenia (presence of abnormally low number of a type of white blood cells called neutrophils). A report indicated that German Shepherds and male dogs have a predilection for the disease and the median age is 5.5 years. In another case, a 12-week old Greyhound was also afflicted with acute lymphoid leukemia.

Chronic lymphoid leukemia on the other hand is less proliferative. These cancerous cells can be hardly differentiated from normal small lymphocytes. The prolonged life span of lymphocytes results in the accumulation of these cells. In B-cell chronic lymphoid leukemia where the lymphocytes play a key role in the humoral immune response (immunity that is mediated by secreted antibodies produced in B-cells), the marrow is invaded with mature lymphocytes.

However, the infiltration is much less compared to acute lymphoid leukemia. The T-cell lymphocytes on the other hand, develop in the spleen and bone marrow. The symptoms may include mild anemia and the granulocytes (white blood cells characterized by and platelets may be slightly reduced. Splenomegaly (enlarged spleen) and lymphadenopathy (swollen lymph nodes) may also be present. However, despite being cancerous in nature, these cells are well-differentiated. Paraneoplastic syndromes like monoclonal gammopathies (elevated gamma globulin, immune mediated hemolytic anemia (condition in which the body’s immune system attacks its own red blood cells), pure red blood asplasia (type of anemia affecting the precursors to red blood cells) and sometimes hypercalcemia (elevated calcium level in the blood) may be present.

Symptoms - Apart from those mentioned above other clinical signs for acute lymphoid leukemia may include anorexia, weight loss, polyuria (urge to urinate frequently), polydipsia (increased thirst) and lethargy. But in case of chronic lymphoid leukemia the symptoms may be absent  although some dog owners have reported of lethargy and decreased appetite. Mild lymphadenopathy and splenomegaly may also be noted.

Diagnostic work-ups
- In order to diagnose any form of cancer, it is very important to understand its history, cell morphology and immunohistochemistry. This applies for lymphoid leukemia as well. Apart from this it is also important to have adequate information about the subset of lymphocytes in healthy dogs because the expansion of this same would be a marker for lymphoid leukemia in dogs. Other work-ups include  examination of peripheral blood (circulating blood) and bone marrow. If sufficient bone marrow cannot be obtained by aspiration, bone marrow core biopsy is done. In acute lymphoid leukemia, the bone marrow is obliterated by the over abundance of  lymphoblasts (immature cells that differentiate to form mature lymphocytes).

Treatment:
Acute lymphoblastic leukemia - Aggressive therapy is needed is restore hemastopoiesis (growth of blood cells) because acute lymphoblastic leukemia causes complete compression of the bone marrow. This disease is not amenable to surgery. Therefore chemotherapy is the only treatment of choice. However, efficacious protocols have not been developed in the field of veterinary medicine. Dogs are mostly treated with CHOP-based protocols consisting of cyclophosphamide, hydroxydaunorubicin (Adriamycin), oncovin (vincristine), and prednisone/prednisolone. However, it is believed that with the addition of doxorubicin and L-asparaginase the outcome would improve considerably.

Chronic lymphocytic leukemia
- Due to the slow rate of progression, chronic lymphocytic leukemia is best treated with observation rather than with any active therapy. Treatment is initiated only if the animal is found to be anemic or thrombocytopnic and shows symptoms of lymphadenopathy or hepatosplenomegaly or if there is an overabundance of WBC. The drug most commonly administered is chlorambucil. The dosage varies according to the degree of remission. However, if chlorambucil fails to give desired results the only option available is combination chemotherapy consisting of l-asparaginase, lomustine, and prednisone.

Prognosis
- The prognosis for acute lymphoid leukemia is guarded. One report  indicated that 21 dogs treated with vincristine and prednisone showed a median survival rate of 120 days, while those with lymphocytic leukemia kept under observation showed a median survival rate of 2 years. In another study dogs treated with a combination of vincristine, prednisone and chlrorambucil showed a median survival time of 12 months. However, in the same study 30% dogs showed a median survival rate of 2 years also.

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Reference

Withrow and MacEwen's Small Animal Clinical Oncology - Stephen J. Withrow, DVM, DACVIM (Oncology), Director, Animal Cancer Center Stuart Chair In Oncology, University Distinguished Professor, Colorado State University Fort Collins, Colorado; David M. Vail, DVM, DACVIM (Oncology), Professor of Oncology, Director of Clinical Research, School of Veterinary Medicine University of Wisconsin-Madison Madison, Wisconsin