No abstract

Despite advances in the understanding of the pathophysiology of cytomegalovirus (CMV) infection, it remains as one of the most common infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to determine the genotype of cytokines and chemokines in donor and recipient and their association with CMV reactivation. Eighty-five patients receiving an allo-HSCT from an HLA-identical sibling donor were included in the study. Fifty genes were selected for their potential role in the pathogenesis of CMV infection. CMV DNAemia was evaluated until day 180 after allo-HSCT. CMV reactivation was observed in 51/85 (60%) patients. Of the 213 genetic variants selected, 11 polymorphisms in 7 different genes (CXCL12, IL12A, KIR3DL1, TGFB2, TNF, IL1RN, and CD48) were associated with development or protection from CMV reactivation. A predictive model using five of such polymorphisms (CXCL12 rs2839695, IL12A rs7615589, KIR3DL1 rs4554639, TGFB2 rs5781034 for the recipient and CD48 rs2295615 for the donor) together with the development of acute GVHD grade III/IV improved risk stratification of CMV reactivation. In conclusion, the data presented suggest that the screening of five polymorphisms in recipient and donor pre-transplantation could help to predict the individual risk of CMV infection development after HLA-identical allo-HSCT.

Multiple myeloma (MM) is a very heterogeneous disease, characterized by multiple cytogenetic aberrations on plasma cells (PC) that have been traditionally used to predict the outcome of the disease. A mayor issue on the analysis of PC is the sometimes low infiltration of these cells in the bone marrow that hampers cytogenetic studies. To solve this problem we have optimized a selection strategy based on PC immunomagnetic isolation that has allowed us to lower to 1% the minimal PC infiltration requirement without loss of purity, enabling to perform genetic analysis. In this study, we have analyzed 153 bone marrow samples of patients suspected of MM, collected from February 2015 to May 2017 by the Genetics service of the Complejo Hospitalario de Navarra. Clinical characteristics of the patients and PC immunophenotyping, conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) analyses have been assessed on these samples. In our cohort 90% of the samples had cytogenetic abnormalities, among them 50% presented immunoglobulin rearrangements, 41.9% showed 1q gains, 29.7% showed 1p deletions and 33% presented TP53 deletion.