CLINICAL EFFECTS OF BIOLOGIC RESPONSE MODIFIERS

The clinical use of the biologic response modifiers filgrastim, sargramostim, and regramostim is reviewed. All circulating blood cells are derived from totipotent hematopoietic stem cells. Various biologic response modifiers, including lymphokines and colony-stimulating factors, regulate and activate the lymphoid and myeloid cells of the blood. One of the more important types of blood cell for fighting infection is the neutrophil. Patients with low neutrophil concentrations are at high risk of developing neutropenic fevers and infections. The colony-stimulating factors filgrastim, sargramostim, and regramostim increase the production of circulating neutrophils, and this action is clinically useful in patients undergoing myelosuppressive antineoplastic therapy or bone marrow transplantation and in patients with the acquired immunodeficiency syndrome. Clinical studies of these agents in comparison with antimicrobial prophylaxis or placebo have shown a decreased rate of neutropenic-associated hospitalizations and infections. These agents are also under study for dose intensification of antineoplastics in patients with various solid tumors and for augmenting patient responses to antimicrobial therapy in situations where there is high risk of morbidity and mortality. Sargramostim and regramostim are both granulocyte-macrophage colony-stimulating factors that differ in their degree of glycosylation and source of production, and at high doses they can cause life-threatening adverse effects because they stimulate the production of a broad range of leukocytes. Filgrastim, which stimulates only the production of neutrophils, has been better tolerated, especially at higher doses. Biologic response modifiers hold much promise for improving therapy of certain clinical conditions by decreasing myelosuppressive complications and enhancing responses to other drugs. Even though the agents in this new biotechnological class have similar names, their actions and adverse effects are quite distinct.