Hematopoietic progenitor cell collection after autologous transplant for multiple myeloma: low platelet count predicts for poor collection and sole use of resulting graft enhances risk of myelodysplasia.

Collection of hematopoietic progenitor cells (HPC) after previous autologous hematopoietic progenitor cell transplant (aHCT) was studied in 221 patients with multiple myeloma (MM). With a total of 333 collections, the median number of CD34+ cells collected was 4.7 × 10(6) CD34+ cells/kg, and 74% of the patients collected ≥ 2.5 × 10(6) CD34+ cells/kg. Among 26 variables examined, the strongest predictor for poor collection was a platelet count <100 × 10(6)/l before mobilization (P<0.001). A subsequent aHCT was performed in 154 of the 221 patients. Sole use of HPC procured after aHCT in 86 patients was associated with delayed platelet recovery (P<0.001) and linked to development of myelodysplastic syndrome (MDS)-associated cytogenetic abnormalities (MDS-CA; P=0.027, odds ratio (OR) 10.34) and a tendency towards clinical MDS/acute myeloid leukemia (AML; P=0.091, OR 3.57). However, treatment-related mortality (P=0.766) and time to absolute neutrophil count recovery ≥0.5 × 10(9)/l (P=0.879) were similar to when a pre-aHCT graft was used. Indeed, adding HPC collected before any aHCT neutralized the risk of MDS-CA or MDS/AML. Therefore, we advise generous initial HPC collection to broaden the salvage armamentarium for patients with MM.

Blood clearance kinetics and liver uptake of mononucleosomes in mice.

Nucleosomes generated by apoptosis have become of considerable interest in relation to pathogenesis of systemic lupus erythematosus in mice and humans. Therefore, the fate of circulating mononucleosomes was examined in normal C57Bl/6J mice. The mononucleosomes were prepared from chicken erythrocytes and radiolabeled on the histone component. The removal of nucleosomes from circulation at doses less than 11 micrograms of injected mononucleosomes was rapid, but with increasing doses of injected nucleosomes, the slopes of the removal curves decreased. Liver was the major organ for removal of circulating nucleosomes, accounting for 71.0 to 84.7% of nucleosomes removed from circulation at 10 min. After i.v. injection of nucleosomes, 0.52 +/- 0.15% localized in kidneys. With prior i.v. injection of histones, the glomerular localization of mononucleosomes increased threefold. The clearance of mononucleosomes was decreased sixfold by concurrent injection of ssDNA. These studies show that in mice, circulating mononucleosomes are handled similar to DNA, and they do not avidly localize in glomeruli unless histones have already bound to renal glomeruli.