As of August 31, 2008, 183 NIH-registry donors had undergone 203 filgrastim-assisted large-volume apheresis procedures to collect peripheral blood stem cells (PBSCs) for unrelated NMDP recipients. 163 of 183 (89%) required only a single apheresis procedure to collect an adequate cell dose for transplantation. The mean volume processed per procedure was 19.3 liters, resulting in an average procedure duration of 4.5 hours. Ten of the 183 donors (5%), all female, required a central line for venous access. All donors experienced filgastrim-induced fatigue, insomnia, bone pain, or headache, although in only 6% were these effects considered severe. The peak mean leukocyte count after the standard 5-day filgrastim mobilization cycle was 39,700/uL, and the peak circulating blood stem cell count (CD34+ cell) following filgrastim was 77/uL. Platelet counts fell by a mean of 33% during apheresis, but significant postapheresis thrombocytopenia (less than 100,000/uL) only occurred in 16 of 183 donors (9%), nine of whom underwent two procedures. The mean time to complete recovery from PBSC donation was 1 week, compared with 3 weeks for marrow harvest. Eleven of 16 donors who had donated both marrow and PBSC preferred filgrastim-stimulated apheresis donations to marrow harvest due to the lack of need for anesthesia and hospitalization; in general, pain and discomfort levels were lower with PBSC donation by apheresis than with marrow harvest. NMDP protocol investigators established a vial-based dosing scheme for filgrastim administration, including a minimum dose of 600 and a maximum dose of 1200 micrograms per day, with intermediate doses based on weight (approximately 10 micrograms per kilogram), but rounded to the nearest vial content as supplied by the manufacturer. This scheme limits toxicity at the upper end of dosing, increases CD34 mobilization efficacy at the lower end of dosing, and prevents drug wastage while maximizing dose-response relationships in the intermediate dosing range. In an analysis of the effect of donor demographic factors on stem cell mobilization response to filgrastim, higher total filgrastim dose, greater donor weight, and greater pre-filgrastim platelet count were strongly associated with higher peak CD34 cell mobilization responses, whereas Caucasian ethnicity, female gender, and increasing age were associated with poorer CD34 responses. The ability to use these factors to predict CD34 cell mobilization outcomes has resulted in optimization of filgrastim dosing schedules and apheresis processing volumes, and increased the lieklihood of obtaining robust CD34 cell apheresis components for transplant. Analysis of NMDP recipient outcomes shows that PBSC transplants are associated with reduced times to engraftment and improved acute transplant-related morbidity compared with marrow transplants. However, GVHD incidence and severity are increased with PBSC versus marrow grafts, so that overall survival at one year is not different among the two types of unrelated transplants. Administrative and statistical support for this study is provided by the NMDP National Office. Filgrastim is provided under an IND agreement with Amgen (BB-IND #6821).
