Discrepancies between the percentage of plasma cells in bone marrow aspiration and BM biopsy: Impact on the revised IMWG diagnostic criteria of multiple myeloma

Moon SY, et al. Ann Lab Med. 2014 Jan;34(1):7-14. http://dx.doi.org/10.3343/alm.2014.34.1.7

Lee N, et al. Ann Lab Med. 2015 Nov;35(6):563-569. http://dx.doi.org/10.3343/alm.2015.35.6.563

Background: The effect of alcohol on the outcome and fibrinolysis phenotype in trauma patients remains unclear. Hence, we performed this study to determine whether alcohol is a risk factor for mortality and fibrinolysis shutdown in trauma patients. Materials and methods: A total of 686 patients who presented to our trauma center and underwent rotational thromboelastometry were included in the study. The primary outcome was in-hospital mortality. Logistic regression analysis was performed to determine whether alcohol was an independent risk factor for in-hospital mortality and fibrinolysis shutdown. Results: The rate of in-hospital mortality was 13.8% and blood alcohol was detected in 27.7% of the patients among our study population. The patients in the alcohol-positive group had higher mortality rate, higher clotting time, and lower maximum lysis, more fibrinolysis shutdown, and hyperfibrinolysis than those in the alcohol-negative group. In logistic regression analysis, blood alcohol was independently associated with in-hospital mortality (odds ratio [OR] 2.578; 95% confidence interval [CI], 1.550–4.288) and fibrinolysis shutdown (OR 1.883 [95% CI, 1.286–2.758]). Within the fibrinolysis shutdown group, blood alcohol was an independent predictor of mortality (OR 2.168 [95% CI, 1.030–4.562]). Conclusions: Alcohol is an independent risk factor for mortality and fibrinolysis shutdown in trauma patients. Further, alcohol is an independent risk factor for mortality among patients who experienced fibrinolysis shutdown.

To examine the immune cell profile in the bone marrow of systemic lupus erythematosus (SLE) patients and to assess its clinical relevance. Sixteen bone marrow samples from 14 SLE patients were compared with seven healthy control samples. The numbers of immune cells and apoptotic cells in the bone marrow were examined by immunohistochemistry. The association between immune cell subsets and clinical features was investigated. CD4+ T cells, macrophages and plasma cells were more common in the bone marrow of SLE patients than in healthy controls (p = 0.001, p = 0.004 and p < 0.001, respectively). Greater numbers of CD4+ T cells and macrophages were associated with high-grade bone marrow damage. The percentage of apoptotic cells in bone marrow of SLE patients was significantly higher than that in controls (p < 0.001) and was positively correlated with the number of plasmacytoid dendritic cells (p = 0.013). Increased number of plasma cells along with high interleukin-6 expression was correlated with anti-double stranded DNA antibody levels and the SLE disease activity index (p = 0.031 and 0.013, respectively). Bone marrow from SLE patients showed a distinct immune cell profile and increased apoptosis. This, coupled with a correlation with disease activity, suggests that the bone marrow may play a critical role in the pathogenesis of SLE.

Background: Concentrations of 6-thioguanine (6TG) nucleotides and 6-methylmercaptopurine (6MMP) nucleotides in RBCs were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay was validated for clinical use and was applied to blood samples from patients taking mercaptopurine (6MP). Methods: RBCs were hemolyzed and deproteinized using perchloric acid, followed by heating for the hydrolysis of nucleotides, and the resultant base was measured using LC-MS/MS. Precision, recovery, linearity, matrix effect, and limit of quantification was validated for clinical application. Our results were compared with another institution's established LC-MS/MS assay. We measured the concentrations of 6TG and 6MMP in RBCs of pediatric patients with acute lymphoblastic leukemia (ALL), and the clinical impact of those metabolites was investigated. Results: The imprecision coefficient of variations of 6TG and 6MMP were 5.7%–8.1%, and the bias was within 5%. Lower limits of quantification were set at 54 ng/mL for 6TG and 1036 ng/mL for 6MMP. Correlation coefficients for 6TG and 6MMP were 0.997 and 1.0 in a comparison study. For clinical proof-of-concept, 74 blood samples were collected from 37 pediatric ALL patients receiving maintenance therapy. Concentration of 6TG ranged from 16.1 to 880 pmol/8 × 10⁸ RBCs and that of 6MMP from 55 to 20,937 pmol/8 × 10⁸ RBCs. The 6MP metabolites were not correlated with WBC or absolute neutrophil count. On the other hand, the higher 6MMP level was associated with elevated alanine aminotransferase and aspartate aminotransferase. Conclusions: In this study, an assay for the quantification of 6TG and 6MMP in RBCs was established and applied to pediatric ALL patients. Interindividual variability in 6MP metabolite concentrations was considerable and associated with elevation of liver enzymes, which may be useful in the clinical monitoring of 6MP maintenance therapy in pediatric ALL patients.