A Study Of The Natural History Of Acute Leukemia With Special Reference To The Duration Of The Disease And The Occurrence Of Remissions

Abstract

A review has been made of relevant available publications on acute untreated leukemia. Estimates on the incidence and prevalence of acute leukemia, by age, sex, and cell type have been presented. The clinical features and laboratory findings have been reviewed with the intent of providing features which might be useful in the evaluation of new therapeutic agents. Available base-line data are presented. A total of 102 spontaneous first remissions in leukemia have been analyzed. Such remissions can occur at all ages, in both sexes, and in all common types of leukemia. These remissions most frequently follow an incident which could be interpreted as “adrenal stress” and clinically appear to resemble in character those produced by ACTH or cortisone. The median duration of such spontaneous remissions is 6.6 weeks, statistically not different from a median duration of 5.2 weeks for 54 cortisone-ACTH remissions reviewed. It is suggested that the mechanism of spontaneous remissions is through the endogenous production of “therapeutic” quantities of adrenal hormones. Remissions have been sporadically observed in acute leukemia almost as long as the disease has been recognized. Eisenlohr in 1878 (Virchows Archiv Section A: Pathological Anatomy and Histology 73 (1878) 56-73) noted the typical pattern of remission. A 19-year-old male was seen with a remarkable leukocytosis and severe anemia (leukocytes nearly equal in number to erythrocytes), hepatomegaly and splenomegaly. A febrile illness supervened, followed by a decrease in the leukocytosis and a regression of organ enlargement. Heuck’s patient of 1879 (Virchows Archiv Section A: Pathological Anatomy and Histology 73 (1879) 475-496) followed a similar course, but in this instance apparatus was available for estimating the decrease in leukocyte counts. Of the 102 cases of spontaneous remission analyzed (48 adults and 54 children), 51 cases collected by Southam et al. (Cancer 4 (1951) 39-59) and 51 cases collected from the literature, factors associated with spontaneous remission were tabulated. Pyogenic infections occurred in 23 patients (8 adults, 15 children), fevers of unknown etiology occurred in 5 patients (1 adult, 4 children), and viral diseases occurred in 10 patients (chickenpox in 3 children, measles in one child, feline leukopenia in 2 children, and infectious mononucleosis in 4 adults) prior to remission. Hence, in 38 of 76 remissions in which a definite antecedent event could be found, the remission was preceded by a febrile illness. Transfusions preceded remission in 17 cases (usual transfusion in 8 adults and 5 children, exchange transfusion in 2 adults and 1 child, marrow transfusion in 1 adult). In 10 cases, various extracts had been used prior to observed remissions (bone marrow in 1 adult and 3 children, urine or feces in 1 adult and 2 children, pentonucleotides in 2 children, and adrenal extract in 2 children). In 4 cases non-specific trauma were antecedent events, and in 7 cases, various agents (nitrogen mustards, urethane, arsenic and B12, folic acid) were used prior to a remission.