Leukocytosis and the Leukemias

Leukocytosis and the Leukemias

The term leukocytosis refers to an increased level of WBCs in the circulation. Typically, only one specific cell type is increased. Usu-ally, because the proportions of several types of WBCs are small (eg, eosinophils, basophils, monocytes), only an increase in neu-trophils or lymphocytes can be great enough to elevate the total WBC count. Although leukocytosis can be a normal response to increased need (eg, in acute infection), the elevation in WBCs should decrease as the need decreases. A prolonged or progressively increasing elevation in WBCs is abnormal and should be evaluated. A significant cause for persistent leukocytosis is malignancy.

Hematopoiesis is characterized by a rapid, continuous turnover of cells. Normally, production of specific blood cells from their stem cell precursors is carefully regulated according to the body’s needs. 

If the mechanisms that control the production of these cells are disrupted, the cells can proliferate to an exces-sive, potentially dangerous degree. Hematopoietic malignancies are often classified according to the cells involved. Leukemia, lit-erally “white blood,” is a neoplastic proliferation of one particu-lar cell type (granulocytes, monocytes, lymphocytes, or megakaryocytes). The defect originates in the hematopoietic stem cell, the myeloid, or the lymphoid stem cell. The lymphomas are neoplasms of lymphoid tissue, usually derived from B lympho-cytes. Multiple myeloma is a malignancy of the most mature form of B lymphocyte, the plasma cell.

The common feature of the leukemias is an unregulated pro-liferation of WBCs in the bone marrow. In acute forms (or late stages of chronic forms), the proliferation of leukemic cells leaves little room for normal cell production. There can also be a pro-liferation of cells in the liver and spleen (extramedullary hematopoiesis). With acute forms, there can be infiltration of other organs, such as the meninges, lymph nodes, gums, and skin. The cause of leukemia is not fully known, but there is some evi-dence that genetic influence and viral pathogenesis may be in-volved. Bone marrow damage from radiation exposure or from chemicals such as benzene and alkylating agents (eg, melphalan [Alkeran]) can cause leukemia.

The leukemias are commonly classified according to the stem cell line involved, either lymphoid or myeloid. They are also classified as either acute or chronic, based on the time it takes for symptoms to evolve and the phase of cell development that is halted (ie, with few WBCs differentiating beyond that phase).

In acute leukemia, the onset of symptoms is abrupt, often oc-curring within a few weeks. WBC development is halted at the blast phase, so that most WBCs are undifferentiated or are blasts. Acute leukemia progresses very rapidly; death occurs within weeks to months without aggressive treatment. In chronic leukemia, symptoms evolve over a period of months to years, and the majority of WBCs produced are mature. Chronic leukemia progresses more slowly; the disease trajectory can ex-tend for years.