Changes in the Human Leukocyte Count During X-Ray Therapy for Cancer and Their Dependence Upon the Integral Dose

Abstract

That x-rays depress the leukocyte count is well known, but the dependence of this phenomenon upon the dose rate, the tissue dose, the integral dose, and the kind of tissue irradiated has not been fully analyzed. The gross changes in the cell counts of patients receiving fractionated treatment for various types of malignant growth were described by Gloor and Zuppinger (10) and Schmitz (27), and in more detail by Kornblum, Boerner, and Henderson (15, 16). Consistent changes in the basophils, eosinophils, and monocytes were not observed. The neutrophils rarely fell below 2,500, but the lymphocyte count frequently declined to the range of 500–1,000. Kornblum et al. (15) noted that irradiation of the head and neck tended to produce smaller changes in the counts than irradiation of the trunk, where larger fields were employed. All cell counts returned to approximately normal levels at about five weeks after treatment. Schmitz commented that in twenty-three years of experience with 6,000 patients he had seen only one case of fatal leukopenia, which occurred in a woman taking amidopyrine. The quantitative relationship between change in lymphocyte count and integral dose has been examined in two studies: Bush (3) reported the average lymphocyte count in 26 cases during treatment to the head and neck, and Price (25) made a similar study of 16 patients receiving irradiation to the pelvis and lower abdomen. The data of these investigators are shown in Figure 1 and may be used to emphasize several questions. The rate of fall in the lymphocyte count differed considerably in the two series. Was this due to the difference in integral dose, in integral dose rate, or local tissue factors? Also to be explained is the mechanism by means of which partial-body irradiation, for example limited to the neck, can disturb the function of a system as widely dispersed as the lymphatic. Methods X-Ray Dosage: The term tumor dose refers to the average tissue dose absorbed in the region of the tumor. Mayneord (19) introduced the term integral dose to specify all of the radiation absorbed within the body. A similar basic concept underlies the term volume dose, used by Ellis (8). Mayneord and Ellis have argued that, while the tumor dose may be the decisive factor in determining the chance of cure, the integral dose may be the decisive factor in determining the systemic reaction to a course of therapy. Specific integral dose, a new term, is introduced below; it is defined as integral dose per kilogram of body weight. The integral dose is the product of mean tissue dose in roentgens times total grams of tissue, the basic unit being the gram-roentgen (gram-r). The megagram-r is equivalent to about 2 calories. The integral dose was estimated by applying the basic principles discussed by Mayneord (19, 20), and also by Happey (12), and is considered to be a useful relative measure.