Leukemia is generally regarded as cancer of the blood-forming organs, specifically those concerned with the production of the various white blood cells.

It has certain rather unique features which make it important to the physician:

1. Although still relatively rare, leukemia has shown a definite sharp increase in incidence in the past two decades.

2. As far as is known at the present time, the disease is systemic from its very inception. This is contrary to the prevailing concept of most other forms of cancer. It thus never provides a localized focus which can be attacked aggressively with surgery or x-ray therapy with hope of cure.

3. Virtually every tissue in the body is involved by the leukemia process, and the clinical manifestations may be extremely varied.

4. Despite its relative rarity, leukemia is quite well known to the public, and it seems to have an unusual ability to arouse fear and dread.

Epidemiology. Incidence

Mortality

Rates

Age

Trend Last Ten Years

Increases are apparent for both men and women. The mortality rate for the age group 60 and above, men and women combined, has more than doubled in the last twenty years rising from 12.3 per 100,000 in 1940 to 27.2 per 100,000 in 1959.

Etiology

The etiology of most leukemia as it occurs today is unknown. However, a number of etiologic factors, most of them having ionizing radiation as the common denominator, are known. As far as can be determined, these account for a relatively small fraction of leukemia cases. Nevertheless, they represent a definite hazard, and many believe that they are responsible for the recent progressive increase in the incidence of the disease.

Radiation

Exposure to radiation usually must be fairly intense, recurrent, or chronic. It may take a number of forms.

1. Therapeutic, an incidental feature of radiation therapy for certain conditions, such as:

(a) Enlarged thymus gland in children (also may predispose to subsequent cancer of the thyroid gland)

(b) Ankylosing spondylitis

2. Diagnostic, in the course of pelvimetry during obstetric care. In this instance the hazard is not to the mother but to the unborn child in utero who has an increased risk of developing leukemia in subsequent life.

3. Other forms

(a) There are a number of occupations in which radiation exposure is or was significant. Radiologists are said to exhibit an increased tendency (some estimate up to ten times greater) toward the development of leukemia than other physicians.

(b) The survivors of the atomic explosions at Hiroshima and Nagasaki have displayed a leukemia incidence many times above that normally encountered.

(c) In these days of increased radiation hazards (e.g., strontium 90 and others in fall-out), there may be many other sources of exposure in food, drink, atmosphere, etc. that can be only speculated upon at the present time.

Chemicals

A number of cases of leukemia have been attributed to exposure to a variety of toxic chemicals, such as benzol, pyridine, aniline dyes, and certain volatile solvents.

Viruses

Intense interest has developed in recent years in the possibility of a viral etiology for human leukemia. Such speculation is based almost exclusively on animal observations, however. It is an interesting hypothesis that must await correlation with evidence in human beings.

Polycythemia rubra vera and lymphosarcoma

A certain percentage of patients with polycythemia rubra vera or lymphosarcoma will eventually develop the clinical and hematologic picture of leukemia. It has been estimated that 10 to 20% of patients with polycythemia rubra vera may eventually develop chronic myelocytic leukemia. In the case of lymphosarcoma, lymphatic leukemia may supervene, especially in children.

Classification

There is no entirely satisfactory classification of leukemia. The over-all group of illnesses is usually subdivided according to the following:

1. Rapidity and intensity of clinical course, i.e., acute or chronic (some add subacute).

2. Predominant cell type, i.e., lympohcytic, myelocytic, monocytic, etc. Often, especially in the acute leukemias, no such cellular distinction is possible.

Frequency, Age, And Sex Distribution Of Various Types

1. Acute leukemia is most frequent among young adults and children, especially those under the age of 5 years. Both sexes are affected in equal proportion.

2. Chronic myelocytic leukemia is more common in the persons between 25 and 50 years of age. It is somewhat more common among males (60:40 ratio).

3. Chronic lymphocytic leukemia is the predominant type beyond the age of 50 years. It predominates in males in a ratio of about 3 to 1.

4. Chronic leukemia is about twice as frequent as the acute variety.

Pathologic Mechanisms

The fundamental defect in leukemia is the marked and unrestrained proliferation of normal and abnormal white blood cells of one type or another. This results in pathophysiologic alterations which can be classified under one of three headings:

1. Increased metabolism due to the increased oxygen consumption of the abnormal white blood cells, as well as their increased rate of production and destruction

Symptoms related to this include the following:

(a) Fever

(b) Weight loss

(c) Tachycardia

(d) Perspiration

(e) Weakness

2. Impairment of bone marrow function (myelophthisis) due to the presence of large masses of leukemia cells. This may be reflected in the following:

(a) Anemia due to decreased production of red blood cells (a hemolytic component may be present also).

(b) Hemorrhagic phenomena due to decreased production of platelets (thrombocytopenia).

3. Infiltration of a wide variety of tissues and organs, resulting in enlargement of the structures, often with secondary mechanical pressure symptoms and derangement of function. The following may be involved:

(a) Spleen

(b) Liver

(c) Lymph nodes

(d) Gastrointestinal tract

(e) Skin

(f) Nervous system

Screening Presumably Well Adults For Leukemia

Chronic leukemia of the myelocytic or lymphocytic type is occasionally encountered in screening asymptomatic, presumably healthy adults. Acute leukemia is ordinarily a rather fulminant and clinically obvious entity for which the physician is consulted with little delay.

Three parts of the routine cancer detection examination may provide leads to the presence of leukemia.

History

1. Subclinical symptoms of nonspecific malaise, lassitude, weakness, bleeding tendency, etc. elicited only by careful questioning.

2. Occupational, therapeutic, or other exposure to radiation or chemical hazards should serve to earmark the patient for special attention.

Physical Examination

1. Pallor

2. Hepatosplenomegaly

3. Lymphadenopathy

4. Bleeding tendency

Laboratory studies Hemogram

1. Anemia as demonstrated by a low hemoglobin level.

2. Leukocytosis as reflected in a high total white blood count.

3. Abnormal differential smear. This may be noted even in the absence of anemia or leukocytosis.

X-Ray Studies

1. The chest x-ray film may occasionally show mediastinal widening or hilar adenopathy.