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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.


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TRANSPLANTATION

Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral-blood mononuclear cells in a canine transplantation model

Lauri Burroughs, Marco Mielcarek, Marie-Térèse Little, Gary Bridger, Ron MacFarland, Simon Fricker, Jean Labrecque, Brenda M. Sandmaier, and Rainer Storb

From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle WA; the Department of Pediatrics, University of Washington, Seattle, WA; the Department of Medicine, University of Washington, Seattle, WA; and AnorMED, Langley, BC.

Peripheral-blood mononuclear cells (PBMCs) mobilized with AMD3100, a CXCR4 antagonist, combined with granulocyte colony-stimulating factor (G-CSF) have reconstituted autologous hematopoiesis in cancer patients following myeloablative conditioning. The engraftment potential of PBMCs mobilized with AMD3100 alone, however, has remained unproven. We therefore studied AMD3100-mobilized PBMCs in a canine model. Four dogs received 920 cGy total body irradiation (TBI) before infusion of autologous AMD3100-mobilized PBMCs (median CD34 cell count, 3.9 x 106/kg). Neutrophil (> 0.5 x 109/L [500/µL]) and platelet (> 20 x/109/L [> 20 000/µL]) recoveries occurred at medians of 9 (range, 7-10) days and 25 (range, 23-38) days, respectively, after TBI, and all dogs had normal marrow function at 1 year after transplantation. To evaluate the long-term engraftment potential of AMD3100-mobilized PBMCs, 5 dogs were given 920 cGy TBI followed by infusion of AMD3100-mobilized PBMCs (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) days and 26 (range, 26-37) days, respectively, after TBI. With a median follow-up of 53 (range, 33-61) weeks, recipients' marrow function was normal, and blood-donor chimerism levels were 97% to 100%. In summary, both autologous and allogeneic AMD3100-mobilized PBMCs led to prompt and durable engraftment in dogs after 920 cGy TBI.


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