Summary:Allogeneic peripheral blood progenitor cell (PBPC) transplants are an alternative to BMT, although G-CSF mobilization dose, timing of pheresis and risk of GVHD are not well defined. We compared harvest characteristics, donor and recipient outcomes and costs of two PBPC transplant strategies with historical controls who received BMT. Twenty donors mobilized with four daily s.c. G-CSF doses (5 g/kg/day) (group 1) and 20 mobilized with 10 g/kg/day G-CSF (group 2) were compared with 20 BM controls (group 3). G-CSF and phereses were well tolerated. Four of 40 PBPC donors required femoral catheter placement. At least 2.5 × 10 6 CD34 + /kg recipient weight were collected with two phereses in 19/20 donors (group 1) and 18/20 donors (group 2). Time to neutrophil (18 vs 20 vs 22 days, P = 0.02) and platelet (21 vs 24 vs 27 days, P = 0.005) engraftment was shorter in the PBPC groups (group 2 vs group 1 vs group 3) but secondary engraftment outcomes were not different. The incidence of grade 2-4 aGVHD was higher in the low-dose G-CSF group (group 1) but there was no difference in cGVHD, 100-day or 1-year survival. The mean PBPC transplant cost (group 1) at first hospital discharge was less than BM (group 3) ($34 643 vs $37 354) but the mean overall cost for both groups was similar at 100 days ($46 334 vs $46 083). Allogeneic PBPC transplant with short course, low-dose G-CSF mobilization is safe, feasible and cost equivalent to allogeneic BMT. Keywords: economic analysis; allogeneic peripheral blood transplant Hematopoietic progenitor cells which are capable of reestablishing hematopoiesis after myeloablative chemotherapy circulate in the peripheral blood in low numbers.

Diabetic retinopathy, retinopathy of prematurity and retinal vein occlusion are potentially blinding conditions largely due to their respective neovascular components. The development of real-time in vivo molecular imaging methods, to assess levels of retinal neovascularization (NV), would greatly benefit patients afflicted with these conditions. mRNA hybridization techniques offer a potential method to image retinal NV. The success of these techniques hinges on the selection of a target mRNA whose tissue levels and spatial expression patterns correlate closely with disease burden. Using a model of oxygen-induced retinopathy (OIR), we previously observed dramatic increases in retinal endoglin that localized to neovascular structures (NV), directly correlating with levels of neovascular pathology. Based on these findings, we have investigated Endoglin mRNA as a potential marker for imaging retinal NV in OIR mice. Also of critical importance, is the application of innovative technologies capable of detecting mRNAs in living systems with high sensitivity and specificity. To detect and visualize endoglin mRNA in OIR mice, we have designed and synthesized a novel imaging probe composed of short-hairpin anti-sense (AS) endoglin RNA coupled to a fluorophore and black hole quencher (AS-Eng shRNA). This assembly allows highly sensitive fluorescence emission upon hybridization of the AS-Eng shRNA to cellular endoglin mRNA. The AS-Eng shRNA is further conjugated to a diacyl-lipid (AS-Eng shRNA–lipid referred to as probe). The lipid moiety binds to serum albumin facilitating enhanced systemic circulation of the probe. OIR mice received intraperitoneal injections of AS-Eng shRNA–lipid. Ex vivo imaging of their retinas revealed specific endoglin mRNA dependent fluorescence superimposed on neovascular structures. Room air mice receiving AS-Eng shRNA–lipid and OIR mice receiving a non-sense control probe showed little fluorescence activity. In addition, we found that cells in neovascular lesions labelled with endoglin mRNA dependent fluorescence, co-labelled with the macrophage/microglia-associated marker IBA1. Others have shown that cells expressing macrophage/microglia markers associate with retinal neovascular structures in proportion to disease burden. Hence we propose that our probe may be used to image and to estimate the levels of retinal neovascular disease in real-time in living systems.