Differential effect of continuous versus cyclic maintenance chemotherapy on cytokine-induced myeloid colony growth

Myeloid colony growth by bone marrow cells obtained from pediatric cancer patients was stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interleukin 1 (IL-1). Although patients recovering from cyclic high-dose chemotherapy showed normal colony growth in response to GM-CSF, patients with acute lymphoblastic leukemia (ALL) receiving continuous maintenance chemotherapy at moderate dose had variable but often severe decreases in myeloid colony growth compared with controls. Marrow from all patients and controls demonstrated enhanced colony growth in GM-CSF-stimulated cultures which also contained IL-1. For patients on continuous daily maintenance therapy for ALL, enhancement of myeloid colony growth in response to IL-1 was proportional to the decrease in colony growth in response to GM-CSF. These observations support a possible clinical role for GM-CSF or other direct stimulators of myeloid growth in the patients receiving episodic high doses of chemotherapy, but suggest that alternative strategies may be more effective for those patients receiving chronic moderate-dose chemotherapy.