Harold Tivey

THE NATURAL HISTORY OF UNTREATED ACUTE LEUKEMIA

Untreated acute leukemia is a complex, fatal, neoplastic disease characterized by protean clinical manifestations, a wide diversity of sometimes confusing laboratory findings, and an exceedingly variable time course. Not infrequently the diagnosis is difficult, the management discouraging, and the evaluation of results misleading. While the clinical picture and course of the disease may vary greatly from one patient to the next, the over-all pattern of a group of patients is quite characteristic. The purpose of this review is to examine, in a quantitative fashion, the pattern of untreated acute leukemia, with particular reference to those characteristics which may form a basis for the evaluation of therapeutic agents. While leukemia as a recognized disease is over 100 years old,” 2 , the recorded history of effective palliative treatment of acute leukemia dates from the introduction of Aminopterin by Farber and associates4 in 1948. Since then clinical trials of a number of chemotherapuetic agents have been reported. As some of these compounds have shown an apparent differential success in the treatment of the various morphologic types of leukemia, and even differences in the effectiveness of treatment of the same disease in the adult and the child, it will be necessary to consider the characteristic pattern of each disease in appropriate detail. The ideal basis for evaluation of the natural history of leukemia would be the carefully compiled results of a series of patients selected a t random who were carefully and objectively followed from the onset of disease to death. A random series implies that every patient with acute leukemia has an equal and independent opportunity to be included in the study. As far as can be determined, no such series exists.

Comparative survival times of x-ray treated versus P32 treated patients with chronic leukemias under the program of titrated, regularly spaced total-body irradiation.

It is accordingly essential to examine the limitations of the data from which this review is assembled. Certain sources of bias and deficiencies of reporting severely limit the information from which a complete picture of acute leukemia can be compiled. Diagnosis is frequently incomplete. Criteria6 exist for the morphological differentiation of the several types of leukemia, but the application of these criteria is extremely difficult in the more acute forms, hence many authors report data simply as “acute leukemia.” Data may be combined for experiences on adults and children. No unassailable prior proof is known to exist that the prognosis is identical. Reporting of cases is incomplete in some articles. All cases should be reported, even those moribund upon admission, for most complete evaluation of results.

The relative rates of formation of new leukocytes in patients with acute and chronic leukemias. Measured by the uptake of radioactive phosphorus in the isolated desoxyribosenucleic acid

In the period from January 1941 to July 1951, treatment of 163 patients with chronic leukemia by the method of titrated, regularly spaced total-body irradiation (1, 2) was started. The basic principles of treatment were identical for all of these patients, but some were given spray roentgen irradiation and others internal irradiation by intravenously injected radioactive phosphorus (P32). No difference between the clinical response to x-ray irradiation and to P32 was noted. A comparison was made of the survival times of the two groups to determine if spray irradiation by x-rays offers a better prognosis than equivalent internal irradiation by radioactive phosphorus. Leukemia is a completely disseminated neoplasm, with infiltration of all organs and tissues. It has repeatedly been observed that the feeling of well-being of the patient with this disease is maximal when leukocytosis, hepatomegaly, splenomegaly, anemia, and lymphadenopathy are minimal. To reach all neoplastic cells, total-body irradiation sho...