Leukemia is a malignant neoplasm of hematopoietic tissue originating in and infiltrating the bone marrow.

Leukemia generally involves the peripheral blood, and often infiltrates the spleen, liver, and lymph nodes.

Normal Marrow	Leukemic Marrow

Leukemia is classified into the major categories of acute and chronic leukemia.

Acute leukemia is characterized byproliferation of immature cells or blasts. If untreated, death usually occurs within 6 months in most patients.	Acute Leukemia
Chronic leukemia is a proliferation of mature appearing cells, again in the marrow, peripheral blood, and various organs. The clinical course is relatively indolent, compared with acute leukemia, and ranges from 2-6 years depending on the subtype of the proliferating cell.	Chronic Leukemia

A few common chromosomal abnormalities

** Most common type of AML

The acute and chronic leukemias are further classified according to their cell lineage into two major categories: myeloid and lymphoid.

Thus there are acute leukemias, either acute myeloblastic leukemia (AML) or acute lymphoblastic leukemia (ALL) and there are chronic leukemias, either chronic myelocytic leukemia (CML) or chronic lymphocytic leukemia (CLL).

The acute leukemias are classified using the FAB* Classification (1975;1985 revision).

While classification of the acute leukemias is fairly straight forward, the classification of chronic bone marrow neoplasms is less clear. A classification scheme based on our current knowledge, is presented on the next page.

*French, American, British Classification

Neoplastic clonal proliferations of pluripotent and multipotent myeloid stem cells result in one of the chronic myeloproliferative disorders: chronic myelocytic leukemia (CML), polycythemia vera (PV), myelofibrosis (MF), or essential thrombocytosis (ET).

The chronic lymphoproliferative disorders or leukemias are a diverse group, being of T, B, and natural killer (NK) origin and having variable prognoses.

Leukemia: Introduction - Incidence

Approximately 10% of all malignant neoplasms are leukemias for about 27,800 new cases/year and 18,100 deaths/year (1990). The incidence rate is almost 10 new cases /100,000 people in the US. The number of new cases is split evenly between acute and chronic leukemia.

Of the 27,800 new cases, 2,500 are in children (<15 years). Leukemia occurring in children is almost always acute with a 4:1 ratio of lymphoid to myeloid leukemia. This is the reverse of that seen in adult leukemia.

The incidence of acute myeloblastic leukemia (AML) rises with increasing age and is the most common (80-90%) adult leukemia and 45% of all leukemias.

Acute lymphoblastic leukemia (ALL) peaks at age 4,10% of all leukemias.

Chronic lymphocytic leukemia (CLL) also increases in incidence with rising age, but is rare before the age of 40 and almost never seen in childhood,30% of all leukemias.

Chronic myelocytic leukemia (CML) peaks at age 30-50, but can occur at any age, 15% of all leukemias.

Leukemia: Introduction - Epidemiology/Etiology

The incidence of ALL is almost twice (1.8:1) as high in white as in nonwhite children. There is no apparent predilection for race or sex among the myeloid leukemias.

In the 1st 10 years of life siblings of patients with leukemia have a 4-fold increased risk of leukemia with identical twins having a 20% chance of developing leukemia.

There is approximately a 20 fold increase incidence of leukemia in children with Down's syndrome.

Other disorders (autosomal recessive) associated with leukemia include Bloom's syndrome, Fanconi's anemia, and ataxia telangiectasia (all disorders with defective DNA excision &/or repair).

Immunodeficiency diseases (ataxia telangiectasia; agammaglobulinemia) may also be associated with leukemia.

Etiology is unknown in most cases of leukemia.

There are several animal models for a posssible viral etiology involving retroviruses with oncogene (e.g. Avian Erythroblastosis virus) and without oncogene (e.g. Avian Leukosis virus) involvement. In humans there is strong evidence of a viral etiology for Adult T cell Leukemia/lymphoma associated with HTLV-I (geographically isolated to SW Japan, the Caribbean, and some sections of Africa). African Burkitt's lymphoma/leukemia is associated with the Epstein-Barr virus.

Environmental factors such as irradiation (e.g. increased incidence of leukemia in survivors of the atomic bomb explosions in Japan); early radiologists (9 fold increased risk); patients who have received therapeutic irradiation), chemical toxins (e.g. benzene, ), and drugs (e.g. chloramphenical, phenylbutazone, and especially alkalating agent chemotherapy) have been associated with leukemia.

Leukemia: Introduction - Epidemiology/Etiology

From a morphologic and kinetic stand-point, there is a failure to differentiate and mature into functional hematopoietic cells. There is a loss of feed-back control, resulting in an over proliferation of immature and often functionally abnormal hematopoietic cells. Such cells may lack certain surface/cytoplasmic proteins and enzymes, ie. myeloperoxidase deficient, or produce aberant products, ie. hemoglobin F. It is likely that leukemic cells produce cytokines or growth factors that inhibit normal hematopoietic growth.

The doubling time of leukemic cells can be as short as 4 days because of an espicially large growth fraction. Otherwise these cells divide more slowly than normal cells (an S-phase almost 3 times normal) and have a high rate of cell death

In acute leukemia doubling times may be on the order of 4 days, a newly transformed neoplastic cell can undergo 30 doublings to yield

10 cells (the limit of current standard detection) and 10 additional doublings to get to 10 cells (displacement of normal marrow elements). Thus it might take 40 days or less to evolve from the initial event to fully symptomatic disease.

Doubling times are much lower in CLL which has a paucity of cells in division.

Ineffective hematopoiesis and chemotherapy result in cell death and turnover of nucleic acids, increasing uric acid levels and causing hyperkalemia.

Metabolically active leukemic blasts consume large amounts of oxygen.