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Blood, 1 December 2005, Vol. 106, No. 12, pp. 4002-4008. Prepublished online as a Blood First Edition Paper on August 16, 2005; DOI 10.1182/blood-2005-05-1937.
Submitted May 13, 2005
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA * Corresponding author; email: rstorb{at}fhcrc.org.
Peripheral blood mononuclear cells (PBMC) mobilized with AMD3100, a CXCR4 antagonist, combined with G-CSF have reconstituted autologous hematopoiesis in cancer patients following myeloablative conditioning. The engraftment potential of PBMC mobilized with AMD3100 alone, however, has remained unproven. We therefore studied AMD3100-mobilized PBMC in a canine model. Four dogs received 920 cGy total body irradiation (TBI) before infusion of autologous AMD3100-mobilized PBMC (median CD34 cell count, 3.9 x 106/kg). Neutrophil ( >500/µl) and platelet ( >20,000/µl) recoveries occurred at medians of 9 (range, 7-10) and 25 (range, 23-38) days, respectively, after TBI, and all dogs had normal marrow function at 1 year after transplant. To evaluate the long-term engraftment potential of AMD3100-mobilized PBMC, five dogs were given 920 cGy TBI followed by infusion of AMD3100-mobilized PBMC (median CD34 cell dose, 4.7 x 106/kg) from their dog leukocyte antigen (DLA)-identical littermates. Neutrophil and platelet recoveries occurred at medians of 8 (range, 8-10) and 26 (range, 26-37) days, respectively, after TBI. With a median follow up of 45 (range, 26-54) weeks, recipients' marrow function was normal, and blood donor chimerism levels were 100%. In summary, both autologous and allogeneic AMD3100-mobilized PBMC led to prompt and durable engraftment in dogs after 920 cGy TBI.
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