The National Marrow Donor Program (NMDP) was established in 1987 to (1) create a registry of volunteer, tissue-typed, unrelated bone marrow donors and (2) facilitate matched unrelated donor marrow transplants through a coordinated circuit of donor, collection, and transplant centers. As of April 30, 2000, 3.9 million donors were participating in the registry and 9,600 unrelated marrow transplants had been facilitated. Peripheral blood stem cell (PBSC) components, harvested by apheresis of filgrastim-stimulated donors, provide larger numbers of progenitor cells which engraft more rapidly than marrow-derived cells, and are being increasingly used instead of marrow in the matched sibling transplant setting. Early favorable outcomes in the related-donor setting, particularly in patients with high-risk leukemia, have led to the cautious adoption of PBSC transplants in the unrelated donor setting. The NIH Marrow Donor Center, one of the largest hospital-based donor centers participating in the NMDP network, with 50,062 donors on its registry, is participating in two nationwide NMDP protocols, one for acquisition of filgrastim-stimulated PBSCs for primary unrelated donor transplant, and one for acquisition of PBSCs for second transplants (necessitated by rejection or tumor recurrence after a first transplant). The objectives of these studies are (1) to monitor the safety of filgrastim administration in healthy volunteer donors, (2) to compare the adverse effects of bone marrow versus PBSC donation, and (3) to monitor the outcome of matched unrelated-donor PBSC transplants, including time to engraftment, incidence of GVHD, and disease free and overall survival. As of April 2000, 215 NIH unrelated donors had undergone marrow harvest and 13 had undergone PBSC donation for NMDP recipients. Sufficient cells for transplant were obtained in one 12 to 20 liter apheresis procedure in ten of these 13 cases. Two of 13 donors had poor CD34 mobilization responses to filgrastim, and needed two consecutive apheresis procedures to collect the requested cell dose. None of the 13 required a central line. All donors experienced G-CSF-induced fatigue, insomnia, bone pain, or headache, although in only 8 percent were these effects considered severe. Peak mean leukocyte counts after filgrastim were 45 plus or minus 12 x 10 to the ninth power/L, and postapheresis thrombocytopenia (less than 100 x 10 to the ninth power/L) occurred in two of 13 donors (15 percent), both of whom underwent two procedures. The mean time to complete recovery from PBSC donation was 1 week, compared with 3 weeks for marrow harvest. Eight of 13 donors preferred G-CSF-stimulated apheresis donations to marrow harvest due to the lack of need for anesthesia and hospitalization; discomfort of the two procedures was considered equivalent. Recipient outcomes, including time to engraftment, GVHD incidence and severity, and overall survival have not yet been evaluated. 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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