Neutrophil Migration Is Defective During Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Infusion After Autologous Bone Marrow Transplantation in Humans

We have previously reported that continuous intravenous (IV) administration of recombinant granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) to humans following high-dose alkylating agent chemotherapy and autologous bone marrow support (ABMS) results in myeloid bone marrow maturation, accelerated granulocyte recovery, and reduced treatment-related toxicity. However, we found that leukocyte counts declined rapidly after discontinuation of rHuGM-CSF therapy, which suggests possible growth factor effects on leukocyte margination and migration. For these reesons we studied granulocyte margination by using 111In-labeled autologous granulocytes and found similar grenulocyte margination before (21.5% ± 13.4%) and during continuous IV rHuGM-CSF infusion (23.3% ± 9.6%). Phagocytosis of Cryptococcus neoformans end grenulocyte hydrogen peroxide production was similer before end during rHuGM-CSF infusion end similar to petients treeted with the seme high-dose chemotherapy end ABMS but not receiving growth factor. However, migration of granulocytes to a sterile inflammatory site was merkedly reduced during continuous rHuGM-CSF infusion (1.2 ± 0.9 WBCs/cm2, 24 hr) as compered with beseline (39.6 ± 17.7 WBCs/cm2/24 hr; P < .0008). These findings may be of relevance when extravascular granulocytes are required for host defense.