STIMULATION TESTS FOR THE BONE-MARROW NEUTROPHIL POOL IN MALIGNANCIES

It has been known for decades that blood neutrophilia occurs after the administration of etiocholanolone, adrenocortical steroids, and endot oxins. Neutrophil leukocytosis in general may be due to several mechan isms such as increased stimulation of the myelopoiesis, increased rele ase from the marrow, a shift from the marginated to the circulating po ol (demargination), prolongation in the peripheral half-life, and decr eased migration of neutrophils from the blood to the tissue. However, the principal cause of the neutrocytosis for each of the above mention ed agents is increased release of neutrophils from the bone marrow res erves. Since a sufficient reserve capacity is a prerequisite for optim al defenses against infections, the marrow response has been used to e stimate the dose of chemotherapy expected to be tolerated without life -threatening neutropenia. However, none of the above ''test substances '' have gained widespread use due to adverse reactions or undesirable effects on neutrophil function. Recent progress in biotechnology has d eveloped recombinant human (rh) hematopoietic growth factors ready for clinical use. Marrow myelopoiesis is stimulated by granulocyte colony -stimulating factor (rhG-CSF) and granulocyte-macrophage CSF (rhGM-CSF ). The immediate effect, however, is mobilization of mature neutrophil granulocytes to the blood. Bone marrow cellularity seems to influence the neutrophil number mobilized during 24 hours by one subcutaneous i njection of either rhG-CSF or rhGM-CSF. A recent pilot study has sugge sted such a ''24 hour stimulation test'' to predict severe neutropenia following cyclic chemotherapy. This concept is illustrated by two cas e reports. The ''stimulation test'' suggests that we may devise strate gies to define patient subsets which may benefit from prophylactic gro wth factor administration during cyclic chemotherapy.