Endotoxin stimulation in patients with lymphoma: correlation with the myelosuppressive effects of alkylating agents.

Estimates of the bone marrow granulocyte reserve were made in 97 patients with lymphoma utilizing the endotoxin Pyrexal. Normal granulocyte responses were observed in most patients who had not received prior myelosuppressive therapy. Patients with lymphosarcoma responded as well as those with Hodgkin’s Disease. All patients with Ieukopenia due to previous therapy or marrow infiltration failed to respond. In the absence of leukopenia only 47#{176}/o of previously treated patients achieved normal responses. The severity of granulocytopenia produced by intravenous alkylating agent therapy was correlated with pretreatment Pyrexal responses. Patients with normal granulocyte reserves, as demonstrated by this test, tolerated subsequent chemotherapy with significantly less severe granulocytopenia (p <0.02) than patients with abnormal test responses. Nadir granulocyte values below 1000 cells/cu mm developed in 7 of 33 patients with normal Pyrexal responses and in 11 of 15 abnormal responders, despite comparable pretreatment granulocyte values. T HE SUCCESSFUL CHEMOTHERAPY of patients with lymphoma is frequently limited by the degree of bone marrow suppression that effective agents regularly produce. While our ability to prevent the complications of anemia and thrombocytopenia with red blood cell and platelet transfusion has improved, the dangers of increased morbidity and potential mortality due to the infectious complications of granulocytopenia have remained less amenable to replacement therapy. Despite advances in antibiotic therapy, infectious complications remain the chief hazard of aggressive chemotherapy; frequently the extent of the granulocytopenia produced by a given dose of drug may not be reliably predicted from the peripheral blood count or the cellularity of a bone marrow aspirate. Attempts to evaluate more accurately the bone marrow granulocyte reserve and to predict the myelosuppressive effects of antineoplastic agents have been made with purified bacterial endotoxin (pyrexal)1 and more recently etiocholanolone,2 a naturally occurring pyrogenic steroid. Administration of these compounds results in mobilization of granulocytes from the marrow into the