Bone Marrow Transplantation, (1998) 21 , 1091–1095  1998 Stockton Press All rights reserved 0268–3369/98 $12.00 http:/ / www.stockton-press.co.uk/ bmt G-CSF serum pharmacokinetics during peripheral blood progenitor cell mobilization: neutrophil count-adjusted dosage might potentially improve mobilization and be more cost-effective LB Faulkner, F Tucci, A Tamburini, V Tintori, AA Lippi, F Bambi, F Malentacca, C Azzari, AMG Gelli, F Genovese and G Bernini Hematology-Oncology Service and Blood Bank, Department of Pediatrics, University of Florence, Ospedale Pediatrico A Meyer, Florence, Italy Summary: The optimal dosing schedule of G-CSF for peripheral blood progenitor cell (PBPC) mobilization is still under investigation although many centers use 10 g/kg/day in a single subcutaneous dose. However, G-CSF clearance increases with increasing absolute neutrophil count (ANC). Hence a G-CSF dosage adjusted to ANC might be a reasonable approach. We measured G-CSF trough serum levels by sandwich ELISA assay at different ANCs in eight patients undergoing treatment with fil- grastim at 10 g/kg/day in a single subcutaneous dose. A total of 26 samples were analyzed, and a strong corre- lation between increasing ANC and decreasing G-CSF levels was found by linear regression analysis (P  0.0003, r 2 = 0.4199). For ANC values above 5000/l the trough serum levels, ie 24 h after administration, were consistently below the level that provides maximal clonogenic precursor stimulation in vitro (10 ng/ml). Serial serum G-CSF measurements performed in three patients at 0, 3, 6, 9 and 24 h after G-CSF adminis- tration, showed a reduction of the area under the curve (AUC) with increasing ANC. For an ANC of 20 000/l or greater, the G-CSF serum level fell under the maxi- mal in vitro stimulation threshold of 10 ng/ml within 12 h. This preliminary pharmacokinetic data seems to suggest that an ANC-adjusted G-CSF dosing schedule might improve the design of PBPC mobilization regimens. Keywords: granulocyte colony-stimulating factor; phar- macokinetics; peripheral blood progenitor cells; hemato- poietic stem cell transplantation; CD34; administration There is no general agreement as to the optimal dosing schedule of rhG-CSF for the purpose of PBPC mobiliza- tion. Doses ranging from 2 g/kg/day to 60 g/kg/day starting at different time points prior to PBPC collection have been associated with PBPC mobilization. 1–10 Many centers use 10 g/kg/day in a single subcutaneous dose, Correspondence: Dr LB Faulkner, Sezione di Oncoematologia, Ospedale Meyer, Via L Giordano 13, 50132 Firenze, Italy Received 12 August 1997; accepted 29 January 1998 which is higher than the dose generally employed to treat granulocytopenia. 5 Other hematopoietic growth factors potentially active in mobilizing hematopoietic progenitors (interleukins 3 and 1, granulocyte–macrophage colony-stimulating factor, stem cell factor etc) are generally less well tolerated, have activi- ties that may not be restricted to the hematopoietic system or might have the potential to stimulate the underlying malignancy. 11 Recombinant human G-CSF has been exten- sively studied and has been in clinical practice for more than 10 years. Its side-effects are mild and thoroughly characterized and it is well tolerated at doses up to 70 g/kg/day. 12,13 Its activity seems to be restricted to the hematopoietic system, and there is no evidence so far that it might hasten tumor progression. Even though growth factor combinations might very effectively mobilize PBPC, 14 G- CSF as a single agent remains at present the most widely employed hematopoietic stimulating factor for this purpose. However, G-CSF pharmacokinetic properties have not been adequately taken into account in this context. The clearance of G-CSF varies with the neutrophil count, ie G-CSF clear- ance increases with increasing ANC. 15–17 In fact, the ANC- dependent pharmacokinetics of G-CSF might be par- ticularly relevant in the stem cell collection setting in which very high neutrophil counts (20 000–30 000/l) are fre- quently reached. Thus a G-CSF dosage adjusted to ANC might provide a more rational approach in this context. At the Children’s Hospital of Florence we have analyzed G-CSF serum levels during mobilization in a group of pediatric cancer patients undergoing PBPC collection. To our knowledge this is the first study of G-CSF pharmaco- kinetics during PBPC mobilization. Patients and methods Patient characteristics Eight patients with refractory or recurrent malignancies were studied. For patient characteristics see Table 1. Informed consent was obtained from the patients or their parents.