Reaction of human granulopoiesis to high-dose cyclophosphamide therapy.

The reaction pattern of an unperturbed human granulopoiesis to pulses of high-dose chemotherapy (cyclophosphamide 2000 mg/m2 plus vincristine 1.4 mg/m2 or adriamycin 20 mg/m2) was serially studied in 6 patients. The stem cells committed to granulopoiesis (CFU-C) of the bone marrow and the cells of the proliferative granulocytic marrow pool were considerably reduced during the first 8 days. Granulopoietic regeneration was first recognizable by increased proliferative activity of bone marrow CFU-C (3H-thymidine technique). The cytotoxic drug-induced injury to the early compartments of granulopoiesis, and granulocytic regeneration proceed sequentially through the ensuing, increasingly differentiated granulocytic compartments. In the peripheral blood, depletion and repletion of the CFU-C pool precede the corresponding changes of segmented neutrophils by 7 to 9 days; during granulocytic regeneration, peripheral blood CFU-C show a transient greatly overshooting decrease.