Leukemia.
Synonym:—Leucocythemia.
Definition:—A condition in which, while there is a decrease in the red blood corpuscles, there is also marked increase in the white corpuscles, with pathological alterations in the spleen, in the lymphatic glands, and in the marrow of the bones. When these changes occur in the spleen and marrow together, the condition is called spleno-medullary or myelogenous leukemia. When in the lymphatic system it is called lymphatic leukemia.
It should be borne in mind that the above distinctions are not always plainly marked. There are cases in which the bone marrow is altered, but there is no disease of the lymphatics, and yet the character of the blood is that of the lymphatic disorder.
History:—This disease has had an interesting history. Bichat, at the beginning of the last century, described a condition of the blood which is now found in leukemia. Later it was described by other writers as suppurative hematitis. Donne, still later, and J. Hughes Bennett, about 1850, described it, the latter more fully, but both with the idea that the pale color of the blood was caused by the presence of pus cells. Bennett named it leucocythemia, Virchow discovered the real pathology of the disease about 1852 and named it leukemia.
Etiology:—The exact cause of this disease has not as yet been determined. Efforts have been made to discover a specific microbic or parasitic origin for the disorder, but these have failed. It occurs among all classes of people, perhaps somewhat more commonly among the Jews, more frequently in males than in females in the proportion of two to one, and during middle life—between thirty-five and fifty years of age. It has followed severe injury, and especially blows directly over the spleen. It has followed gastric and intestinal ulceration, and has appeared in many cases where there was undoubted autointoxication. Vehsemeyer studied 600 cases with reference to this condition as a cause. It has followed syphilis and chronic malaria, and has been supposed to be associated with tuberculosis. It has attacked those who have long engaged in active physical exercise, and those whose brains and nervous systems were overworked. It has followed severe mental strain, grief, shock and loss of fortune. In women it follows complicated pregnancies, or it may occur during the menopause. In a few cases it has occurred in adult children of parents who had suffered from the disease, but heredity is by no means established as a cause.
Symptomatology:—In myelogenous leukemia, among the early symptoms are those of progressive weakness with paleness characteristic of developing anemia. But while these conditions are conspicuous and pathognomonic, these patients are exceedingly well nourished. Among the early local symptoms is splenic hypertrophy; the organ is considerably enlarged and the outline is usually plainly circumscribed. There is considerable fever, the temperature varying from 99° to 102.5° F. As the disease progresses the average daily temperature is higher than at the earlier stage. The onset is rather abrupt in the acute form, and the temperature is higher at the onset than in the chronic form. Hemorrhage is an early symptom. With this there is vertigo, nausea, rapid breathing, with some dyspnea, and either irregular heart action or marked palpitation; the hemorrhage is most commonly from the nose or from the gums, but hemorrhage in the stomach, or intestinal canal, or hemoptyses, may occur; cerebral hemorrhage is not uncommon. With enlargement of the spleen there is also enlargement of the lymphatic glands. The patient has a feeling of general distress, there is pain over the spleen, and tenderness in the long bones, sometimes in the joints, and in the sternum; there is an increase in the pallor, and the anemia becomes a pronounced symptom. The anemic murmurs can be readily heard over the heart.
In chronic leukemia the onset is insidious, extending over a longer period of time than in the acute form, sometimes requiring several months in which to develop the characteristic symptoms. There is a disinclination to physical exercise; later there is languor and pronounced malaise. The patient takes but little interest in the things around him, and complains of serious impairment of the health; has loss of appetite, and later a repugnance to the taking of food, with more or less nausea and occasional vomiting. Diarrhea is not uncommon. The patient complains of slight roaring or noises in the ears; there is vertigo, faintness, exhaustion after exercise, loss of breath, or frequent deep, sighing respiration, and palpitation with irregular action of the heart. With the evolution of this train of symptoms, the patient observes early a hardness and enlargement in the left side of the abdomen, and this is sometimes the first symptom for which he consults a physician. This is accompanied with pain and soreness, and as this enlargement increases there is a corresponding increase in the anemia. The face presents a puffed appearance, and there is edema also of the ankles and perhaps of the hands.
The temperature is usually above normal, although complete intermissions with subnormal temperature are not uncommon. The pulse is usually full and large, but soft and compressible, and slightly increased in rate. In an occasional case the fever may resemble that of typhoid or of some of the acute infectious fevers, having the tongue symptoms as well as some of the enteric symptoms of the former disease. In that form of leukemia which affects the lymphatic glands more positively, the temperature is a marked factor in the disease. It quickly reaches a medium high point and is not reduced by the treatment to any appreciable degree. It quickly assumes a form, with delirium subsultus tendinum and coma, closely resembling a severe typhoid case. From this, however, it can be distinguished by petechia, with the rapidly progressive anemia, and occasionally by a painful stomatitis. The enlargement of the glands is rapidly progressive, but it is not as great as is observed in the chronic form of lymphatic leukemia. There may be renal complications, and occasionally an acute nephritis will develop. The course of this acute form is quite rapid, often terminating in a few weeks.
In the chronic form of this variety the swelling of the lymphatic glands is a conspicuous and pathognomonic symptom. It is first observed in the cervical glands; later it appears in those of the axillae, and still later in the inguinal glands, finally involving all of the lymphatic glands of the body. These glands are soft and tender, occasionally quite painful, but do not, as in Hodgkin's disease, compress the other organs or the nerves or arteries and produce the distressing symptoms of that disorder. There is seldom suppuration of these glands. The spleen is also somewhat enlarged, but disease of this organ is not a conspicuous factor, as in the splenomedullary form.
The failing strength, emaciation and anemia are all progressive, are little benefited by treatment, and are diagnostic of the serious character of the disease. While hemorrhages are not so severe or so general as in the splenomedullary form, they are a serious factor of the disease, especially of the late stages. The course of this form of the disease is from one to three years.
Diagnosis:—The diagnosis is not always simple. There are other conditions which in the main factors closely resemble this. While there is the pallor, the enlarged spleen in the medullary form, and the enlarged glands in the lymphatic form, these are not alone diagnostic. An examination of the blood is absolutely necessary to a positive diagnosis. There are present a greatly increased number of leukocytes, of which a large portion are of the granular, mononuclear variety. There is also an increase in actual number of the polynuclear cells. There are present at the same time neucleated red blood cells. The disease is distinguished from leukocytosis by the increased number of leukocytes in the latter disease, with an absence of myelocytes; from Hodgkin's disease, by the fact that while the lymphatic glands are enlarged in both cases, the glands are not massed or bunched together as in the former disease. There are also some points of resemblance between this disease and a chronic malarial enlargement of the spleen with anemia.
Prognosis:—It is seldom that a case of leukemia recovers. In rare cases, a marked impression upon the progress of the disease may be made by carefully adjusted treatment, and a fatal issue postponed. A very few cases have been reported in which there seemed to be a spontaneous abatement of the progress of the disease and a disappearance of the marked symptoms. A fatal result may be anticipated within three or four years. In the acute form death may occur in from eight to twelve weeks.
Treatment:—The treatment, because of the prognosis, is undertaken without confidence, and consequently is seldom as positively and as energetically directed as it would be if the physician felt that there was a chance of obtaining favorable results. An early diagnosis is of the utmost importance; all the habits of life of the patient should be changed, he should be taken to a mild climate, and should spend, if possible, both his waking and sleeping hours in the open air. The mind must be tranquil and must be occupied only with those things which are pleasant and congenial. If improvement occurs, mental exercise may be increased slowly in agreeable lines. The use of iron tonics, combined with or alternated with arsenic to toleration, and given with full doses of phytolacca decandra, will constitute the medicinal treatment in the main. I would positively impress upon every prescriber to watch vigilantly from the onset of the disease for the exact indications for any of our specific medicines, and to persist in their use with the same positiveness as when prescribing for conditions in which he is confident of cure. There will be indications for aconite during the pyrexia, occasionally for belladonna and bryonia, and nearly always indications for phytolacca. I should certainly give the latter remedy in very large doses. With these, polymnia uvedalia has been given in this disease with good results. Ceanothus, is another remedy that should be tried. Chelidonium and chionanthus will also exercise some influence. At the same time remedies calculated to encourage the function of the blood-making organs are especially desired. Recently grindelia squarrosa is recommended for disorders of the spleen, and it should be thoroughly tried in this disorder.
Within the past two years several noted authorities have treated leukemia with the Roentgen ray, and in all cases they report some benefit and in a number of case marked improvement. It is possible that we may find in some of the chemical rays which are now receiving investigation a means of controlling the hitherto almost fatal progress of this serious malady.
