Granulocyte-Monocyte Colony-forming Capacity of Human Marrow: A Clinical Study

Abstract

A modification of the in vitro culture of marrow cells in soft agar to form granulocyte-monocyte colonies has been applied to human marrow using a constant stimulus of colony-stimulating factor (CSF) in the form of pooled serum from endotoxin-treated C57BL mice (EMS). With this system reproducible increments in colony formation were observed between two concentrations of EMS. The results indicate that the incremental response to two doses of CSF (CSF response ratio) combined with an observation of the number of colonies formed provide a more reliable measurement of colony-forming cells (CFC) than colony counts at a single dose level of CSF. The CSF response ratio in 43 marrow cultures from 34 patients with no obvious disturbance in granulopoiesis was found to be 1.65 (± 0.17 SD). Hodgkin’s disease with normal marrow showed a mean CSF response ratio of 2.04. Two subjects recovering from drug-induced agranulocytosis showed increased CSF response at a time when the blood was still neutropenic and the marrow showed hyperplasia and immaturity of the granulocytic tissue. In contrast, patients with sustained neutropenia and impaired marrow granulopoiesis showed CSF response ratios of less than 1.65. CSF response ratios in chronic myelogenous leukemia averaged 1.72, often with extremely high numbers of colonies per plate. Patients with untreated acute leukemia and marrows replaced by blasts did not form colonies. However, with partial leukemic marrow replacement, lymphoblastic leukemia marrow formed more colonies than did that of myeloblastic leukemia.