As of August 31, 2016, 323 NIH-registry donors had undergone 340 filgrastim-assisted large-volume apheresis procedures to collect peripheral blood stem cells (PBSC) for unrelated NMDP recipients; 11 donors donated PBSC twice, and 9 donated subsequent unstimulated leukocytes. 305 of 323 (94 %) required only a single apheresis procedure to collect an adequate cell dose for transplantation. The mean volume processed per procedure was 19.6 liters, resulting in a procedure average duration of 4.6 hours. A central line was required for venous access in 32 (9.4%) of the 340 procedures. All donors experienced filgrastim-induced fatigue, insomnia, bone pain, or headache, although in only 5% were these effects considered severe. The peak mean leukocyte count after the standard 5-day filgrastim mobilization cycle was 37,000/uL, and the peak mean circulating blood stem cell count (CD34+ cell) following 5-day filgrastim administration was 56.9/uL. Platelet counts fell by a mean of 39 % during apheresis, and significant post-apheresis thrombocytopenia (less than 100,000/uL) occurred during 75 of 340 donations (22 %). The mean time to complete recovery from PBSC donation was 1 week, compared with 3 weeks for marrow harvest. NMDP protocol dictates 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 rounds 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 higher pre-filgrastim platelet count are strongly associated with higher peak CD34 cell mobilization responses, whereas Caucasian ethnicity, female gender, and increasing age are 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 likelihood 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, decreased rates of graft rejection, but higher rates of chronic extensive graft versus host disease compared with marrow transplants, such that there is no difference in overall survival, disease free surivival, or leukemia relapse at three years following transplant 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).
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