Mohr, Amy

Abstract Abstract 970 Despite advances in treatments for patients with non-Hodgkin's lymphoma (NHL), the relapse rates remain high and 40% of diffuse large B-cell NHL (DLBCL) patients die of disease. These patients have variable levels of immunodeficiency that may impact their prognosis. Previously we reported that monocytes in relapsed NHL patients suppress both autologous and allogeneic T cell proliferation and that these monocytes were unable to mature into dendritic cells in vitro. These suppressive functions were associated with increased frequency of CD14+HLA-DRneg monocytes in NHL patients (NHL: 29.4 ± 3.2%, n = 36; healthy donors 7.54 ± 0.97%, n = 27; p < 0.0001). This phenotype is distinct from other myeloid suppressors (Lin−CD33+HLA-DR−) or non-classical monocytes (CD16+), neither of which was different in numbers between NHL and healthy donors. We have now expanded our study cohort and found that the percentage of CD14+HLA-DRneg cells among circulating monocytes was increased in patients with more aggressive disease: DLBCL 37.5 ± 5.11%, n = 16 vs SLL and MALT lymphoma 15.8 ± 4.02%, n = 7; p = 0.01. Two newly diagnosed patients and three patients with localized disease amenable to resection all had frequencies of CD14+HLA-DRneg monocytes closer to that of healthy donors whereas 5 of the 6 patients with low grade NHL that transformed to DLBCL had significantly elevated percentage of these suppressive monocytes (49.1 ± 4.70%). To better understand the mechanism of immune suppression by CD14+HLA-DRneg monocytes, we investigated production of IFN-alpha induced by CpG oligodeoxynucleotide. Monocytes from NHL patients were less effective at IFN-alpha production (0.54 ± 0.22%, n = 4) compared to healthy donors (1.37 ± 0.25%, n = 4; p = 0.04). The corresponding culture supernatants also had a 4-fold reduction in IFN-alpha level by ELISA (p = 0.01). Reduced IFN-alpha production and subsequent decreased stimulatory response may contribute to diminished treatment response to CpG in NHL. Finally, we also found that the frequency of CD14+HLA-DRneg monocytes correlated with increasing plasma levels of arginase I, a known mediator of T cell suppression (n = 16, p = 0.06). Such correlation was not observed for circulating VEGF, IL-6 or IL-10. Taken together we have described a population of immunosuppressive CD14+HLA-DRneg monocytes in NHL patients that is more prevalent in aggressive disease and likely suppresses T cell function through multiple mechanisms including arginine metabolism. This work was supported through the University of Iowa and Mayo Clinic Lymphoma SPORE CA097274 and the Gerstner Family Foundation. Disclosures: Witzig: Novartis: Research Funding.

BackgroundThe use of hematopoietic progenitor cell (HPC) transplant has risen over the past two decades. A variety of adverse events (AEs) of varying severity have been noted during HPC infusions. These AEs have been associated with several factors such as the amount of dimethyl sulfoxide and white blood cells in the HPC product. We performed a single‐institution retrospective analysis to determine the effect of two different HPC infusion techniques, manual push with syringes versus infusion from bags with the aid of gravity, on the occurrence of infusion‐related AEs.Study Design and MethodsInfusions between December 2008 and November 2010 involving peripheral blood HPCs were reviewed. Pertinent clinical and HPC product–related information was recorded. Data were analyzed to determine the incidence of infusion‐related AEs and its association with patient and product‐related variables.ResultsWe found 461 AEs in 645 patients during the study period. A total of 325 (50%) experienced at least one AE. Flushing was the most common type of AE followed by nausea and hypertension. The use of syringe infusion was more commonly associated with AEs (odds ratio, 1.82 [95% confidence interval, 1.32‐2.50]; p = 0.002). Other independent risk factors were cryopreserved products and the amount of polymorphonuclear leukocytes in the product.ConclusionTo our knowledge, this is the first study examining the effect of two different infusion techniques on infusion‐related AEs. Our findings suggest that the use of bags for infusion protected the patients from AEs.