Abstract

AMD3100 (AMD) is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 to its cognate receptor CXCR4 present on CD34+ hematopoetic progenitor cells. Recently, investigators have shown that substantial numbers of CD34+ cells are released into circulation following a single injection of AMD, making this a potentially attractive mobilization agent for both autologous and allogeneic hematopoietic cell transplantation. Mononuclear cells transplanted in G-CSF (G) mobilized allografts mediate both desirable and undesirable post-transplant events (i.e. Graft-vs-tumor and GVHD); therefore, to determine the suitability of AMD mobilized products for allografting, we assessed the cellular content of apheresis collections obtained from the same donors mobilized with AMD vs G. Between 11/03–07/04, 6 healthy donors (male=3, female=3), median age 43 years (range 18–57), underwent a 15–25 liter apheresis following G mobilization (10mcg/kg/d x 5 days); 66–143 (median 82) days later, the same donors underwent repeat apheresis 6 hours following a single subcutaneous injection of AMD (240mcg/kg); the apheresis blood volume processed after AMD mobilization was matched to the volume processed after G mobilization in 5/6 donors. Data on peripheral blood (PB) and apheresis cellular content with both mobilization agents are shown in Table-1. AMD was well tolerated (no > grade I toxicities) and effectively mobilized CD34+ cells in the majority of donors who had a previous successful G mobilization. Both drugs significantly increased PB CD34+ counts and the total WBC count, and absolute neutrophil counts (ANC), monocyte counts (AMC) and lymphocyte counts (ALC) above pre-mobilization baselines. In the PB, the increase in WBC count, ANC, and the CD34+ counts were significantly higher after G mobilization compared to AMD. In contrast, there was a trend towards a higher blood ALC increase following AMD administration compared to G. Apheresis collections mobilized with AMD contained similar numbers of mononuclear cells and CD3+ T-cells, higher numbers of CD19+ B-cells and lower numbers of monocytes and CD34+ cells compared to G mobilized collections; whether prior G mobilization negatively impacted the CD34+ cell content in AMD mobilized grafts can not be determined from this study. One patient failed mobilization with both G (CD34+ pre-count 6 /uL) and AMD (CD34+ pre-count 6 /uL); a trial investigating the efficacy of combining AMD with G in patients who fail to mobilize with G alone is currently being pursued. A detailed phenotypic analysis of lymphocyte subsets mobilized with G vs AMD3100 will be presented in a separate analysis.

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