Alterations of Granulopoiesis Following Chemotherapy

Clonal proliferation of marrow granulocytic progenitor cells (GPC) in vitro and the daily urinary output of granulocytic colony-stimulating factor (CSF) were determined in two patients with acute myeloid leukemia (AML) in remission and one patient with malignant lymphoma receiving monthly pulses of chemotherapy with cytosine arabinoside and 6-thioguanine. During and immediately following therapy, a marked decrease of granulocytic colony-forming capacity (CFC) occurred, with an increase and return to basal levels by 3-4 wk. In the AML patients, the proportion of GPC in DNA synthesis (GPC-S), as determined by the thymidine suicide technique, declined from basal levels (31%-39%) to 0%-26% after 2 days of treatment. This was followed by a sharp rise in GPC-S to 41%-75% 1-3 days posttherapy, with an oscillatory return of GPC-S to basal levels by 3-4 wk. In all courses a marked increase of urinary CSF output occurred during or 1 day posttherapy, concomitant with the rise of the proportion of GPC-S. In the lymphoma patient, an initially high proportion of marrow GPC-S and low CFC anticipated the severe neutropenia which followed therapy. These results provide a basis for determining the efficacy with which cytotoxic drugs destroy proliferative activity of GPC and for assessing the potential for hemopoietic toxicity following chemotherapy.