Granulocyte Reserve following Radiation Therapy as Studied by the Response to a Bacterial Endotoxin.

By SAMUEL HELLMAN AND MARTIN E. FINK M ANY PATIENTS with advanced neoplasms receive radiation therapy and subsequently chemotherapy during the course of their disease. It is known that both of these agents can cause damage to the myebopoietic system. Curreri and co-workers1 have indicated the dangers of administering 5 fluorouracil in patients who have previously received extensive radiation. They feel that these patients are more prone to drug induced bone marrow toxicity. However, there are a great many patients who receive x-ray therapy followed by chemotherapy who fail to demonstrate any evidence of impairment of bone marrow function. Some information is available concerning the alteration of bone marrow within the fields of frradiation.26 The changes in this bone marrow vary with the dose of radiation given, as does the ability to recover. With larger doses the bone marrow is depicted as hypoplastic and fibrotic with little recovery occurring. However, there is no necessary correlation between local bone marrow morphologic change and total bone marrow function. Pyrexal,* a highly purified lipopolysaccharide, an endotoxin derived from Salmonella abortus equi,7 has been used by a number of investigators to study bone marrow function. The leukocytosis following an intravenous injection of endotoxin probably is due to mobilizing the marrow granulocyte reserve. Such mobilization can be used as a test of the size and functional activity of the granulocyte reserve.843 Repeated injections of this material produce a consistent mature granulocyte response without evidence of tolerance. Tolerance does develop to some of the side effects such as fever and chills. Whereas the total number of mature granulocytes entering the systemic circulation in response to the endotoxin appears to remain constant from day to day,11 the percentage of immature forms appearing as a response to the endotoxic stimulus does diminish. Fink and Calabresi12 have recently reported using such a response as a measure of the functional marrow granubocyte reserve in patients who are to receive chemotherapeutic agents. In 16 patients with malignant disease but without evidence of bone marrow involvement by these tumors and who received no previous x-ray or chemotherapy there was a mean granulocyte rise of 5810 cells/cm. (range 2220-10,497 cells/cm.) within 5 hours of injection of the endotoxin. They felt that a mature granulocyte rise of less than 2000 cells per cu. mm. within 5 hours of the injection was ab-