Malignancy may occur at each major stage in the development sequence of the blood cells. In general, the earlier the stage at which the cell is involved by malignancy, the worse the prognosis. Thus, a leukemia whose predominant cell is the myeloblast has a much worse prognosis (if untreated) than one whose predominant cell is the myelocyte.

Leukemia is a term that denotes malignancy of WBCs, although its definition is often extended to include malignancy of any type of blood cell. In many patients with leukemia (including the majority of those with the chronic leukemias), the total number of WBCs in the peripheral blood is increased above the reference range. Acute leukemia was originally defined as a leukemia that, if untreated, would be expected to permit an average life span of less than 6 months. The predominant cell is usually the blast (or closely related cells such as the promyelocyte). In most cases there are more than 25% blasts in the peripheral blood, and for many years this criterion was the usual basis for suggesting the diagnosis of acute leukemia. The major exception was monocytic leukemia, which behaves like acute leukemia even though the number of monoblasts may be very low. Definitive diagnosis was usually made by bone marrow aspiration; this is a necessity when using the French-American-British classification system (discussed later). Chronic leukemia is a leukemia that, if untreated, would be expected to permit an average life span of more than 1 year. The predominant cell forms are more mature; generally, the prognosis is best for chronic leukemias involving the most mature forms. Thus, chronic lymphocytic leukemia (CLL) has a better prognosis than chronic granulocytic (myelocytic) leukemia (CGL).

Subleukemic leukemia is sometimes used to refer to a leukemia in which the total peripheral blood WBC count is within the reference range but a significant number of immature cells (usually blasts) are present.

Aleukemic leukemia is the term used when the peripheral blood WBC count is normal (or, more often, decreased) and no abnormal cells are found in the peripheral blood. The diagnosis of subleukemic or aleukemic leukemia is made by bone marrow examination. More than 30% blasts in the bone marrow usually means leukemia; 10%-30% suggests the myelodysplastic syndrome (discussed later).

Stem cell leukemia or acute blastic leukemia are terms often applied when nearly all the WBCs are blasts and no definite differentiating features are present. Myeloblasts and lymphoblasts are morphologically very similar on peripheral blood smears, and reliable differentiation by morphologic appearance alone is sometimes not possible even by experts. In some cases differentiation is made on the basis of other information, such as the age of the patient and the types of cells accompanying the blasts. Cytochemical stains, monoclonal antibodies, and perhaps chromosome analysis are very helpful. Auer rods are small rod-shaped structures that sometimes are present in the cytoplasm of blasts. Auer rods are diagnostic of myeloid cells, either myeloblasts or the myelomonocytic form of monocytic leukemia.

Both the lymphocytic leukemias and the malignant lymphomas are derived from lymphocytes or lymphocyte precursors; but the leukemias originate in bone marrow, whereas the lymphomas originate in lymphoid tissue outside the marrow, most often in lymph nodes. The lymphomas and their close relative, Hodgkin’s disease, will be discussed later.