Quantification Of Plasma Cells Research Articles

Analysis of Normal Plasma Cell Distribution Across Distinct Age Cohorts Reveals Age-Dependent Changes.

Hematopoietic and stromal cells within the bone marrow (BM) provide membrane-bound and/or soluble factors that are vital for the survival of plasma cells (PCs). Recent reports in murine BM demonstrated the dynamic formation and dispersion of PC clusters. To date, PC clustering in normal human BM has yet to be thoroughly examined. The goal of this study was to determine whether PC clusters are present in human BM and whether clustering changes as a function of age. Quantification of PCs and clustering in BM sections across six different age groups revealed that fewer PCs and PC clusters were observed in the youngest and oldest age groups. PC clustering increased with age until the sixth decade and then began to decrease. A positive correlation between the number of PCs and PC clusters was observed across all age groups. PC clusters were typically heterogeneous for immunoglobulin heavy- and light-chain expression. Taken together, these data demonstrate that PC clusters are present in human BM and that PC clustering increases until middle adulthood and then begins to diminish. These results suggest the spatial distribution of BM PC-supportive stromal cells changes with age.

Circulating Tumor Cells for the Staging of Patients With Newly Diagnosed Transplant-Eligible Multiple Myeloma.

Patients with multiple myeloma (MM) may show patchy bone marrow (BM) infiltration and extramedullary disease. Notwithstanding, quantification of plasma cells (PCs) continues to be performed in BM since the clinical translation of circulating tumor cells (CTCs) remains undefined. CTCs were measured in peripheral blood (PB) of 374 patients with newly diagnosed MM enrolled in the GEM2012MENOS65 and GEM2014MAIN trials. Treatment included bortezomib, lenalidomide, and dexamethasone induction followed by autologous transplant, consolidation, and maintenance. Next-generation flow cytometry was used to evaluate CTCs in PB at diagnosis and measurable residual disease (MRD) in BM throughout treatment. CTCs were detected in 92% (344 of 374) of patients with newly diagnosed MM. The correlation between the percentages of CTCs and BM PCs was modest. Increasing logarithmic percentages of CTCs were associated with inferior progression-free survival (PFS). A cutoff of 0.01% CTCs showed an independent prognostic value (hazard ratio: 2.02; 95% CI, 1.3 to 3.1; P = .001) in multivariable PFS analysis including the International Staging System, lactate dehydrogenase levels, and cytogenetics. The combination of the four prognostic factors significantly improved risk stratification. Outcomes according to the percentage of CTCs and depth of response to treatment showed that patients with undetectable CTCs had exceptional PFS regardless of complete remission and MRD status. In all other cases with detectable CTCs, only achieving MRD negativity (and not complete remission) demonstrated a statistically significant increase in PFS. Evaluation of CTCs in PB outperformed quantification of BM PCs. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible MM.

Evaluation of an open-source machine-learning tool to quantify bone marrow plasma cells

AimsThe objective of this study was to develop and validate an open-source digital pathology tool, QuPath, to automatically quantify CD138-positive bone marrow plasma cells (BMPCs).MethodsWe analysed CD138-scanned slides in QuPath....

MM-069: Autologous Hematopoietic Stem Cell Transplant in Multiple Myeloma: Plerixafor Mobilization and Progression-Free Survival

Context: Plerixafor is a CXCR4 receptor antagonist developed for improving the mobilization of CD34+ cells prior to collection for autologous hematopoietic stem cell transplantation (Auto-HSCT) in hematologic malignancies, used when a high rate of insufficient collection by apheresis is expected. In multiple myeloma (MM), apart from an increase in the number of CD34+ cells, it has been shown a rise in the amount of plasma cells collected. Objective: Our hypothesis is that Plerixafor-mobilized patients and their potentially contaminated product could have an impact on their relapse-free survival. The primary outcome of this study was to evaluate if the addition of Plerixafor to filgrastim (G-CSF+P) for mobilization phase was related to a lower progression-free survival (PFS) compared to patients who received only filgrastim (G-CSF). Design: Observational, retrospective, longitudinal trial that included adults with MM who received Auto-HSCT between January 2012 to May 2019. Mean follow-up for surviving patients was 37 months. Setting: Hospital care, high-complexity center. Patients or other participants: 88 MM patients received Auto-HSCT in the studied period. 28 were excluded due to insufficient follow-up, second transplant, or missing relevant data. Median age was 57 years (range 31-73). A mean of 4.67 (± 2.42) and 6.65 (± 3.17) × 106 CD34+ cells/kg were infused in the G-CSF and G-CSF+P groups, respectively. Interventions: Follow-up after Auto-HSCT. Main outcome measures: Kaplan-Meier analysis to determine PFS and overall survival (OS). Results: Median PFS (n=60) was 24 months. In the subgroup analysis, PFS was 36.3 months for the filgrastim group (n=25) and 21.5 months for patients who received G-CSF+P (n=35; p=0.24). Median OS was 70 months (70 months vs not reached for G-CSF and G-CSF+P groups, respectively, p=0.6). Conclusions: Adding Plerixafor prior to autologous collection in MM showed a tendency towards a lower PFS, and a controlled trial with a larger sample size and longer follow-up is needed to define if this trend becomes statistically significant. Biological studies, such as the quantification of plasma cells and their apoptotic rate could add to the evaluation of the impact of the mobilized product in the relapse rate of MM patients.

A quantitative assessment of primary and secondary immune responses in cattle using a B cell ELISPOT assay

The aim of the study was to build a comprehensive picture of the appearance in the blood stream of Ag-specific plasma cells and memory B cells in the bovine model. For this purpose, we have developed a method allowing the detection and quantification of both cell types within individual calves immunised with ovalbumin. During the primary response, we detected a burst of ovalbumin-specific plasma cells at days 6 and 7 post-immunisation, which was followed by the production of specific Ab, whereas a gradual increase of memory B cells was only detected from day 15. As expected, a boost immunisation performed 7 weeks later induced a quicker and stronger secondary response. Indeed, a burst of plasma cells was detected in the blood at days 3 and 4, which was followed by a strong increase in Ab titres. Furthermore, a burst of memory B cells, and not a gradual increase, was detected at days 5 and 6 post-boost immunisation. Importantly, we showed a strong correlation between the anti-ovalbumin-specific IgG titres detected 5 months after secondary immunisation and the plasma cell numbers detected in the blood at the peak response after secondary immunisation. The detection and quantification of plasma cells following an immunisation/vaccination strategy could constitute a very effective means for predicting the magnitude and longevity of an Ab response.

Morphometric quantification of plasma cells in the intestinal mucosa of children

In an attempt to obtain a sampling procedure of known accuracy for plasma cell quantification, applicable for routine analysis, we counted IgA, IgM and IgG producing cells in the lamina propria of the small intestine of six children by the method II of Aherne (1976), using two sampling procedures. In the first, we determined the number of cells in each one of 200 successive microscopic fields without specifying their localization in the mucosa. Proper tests upon this data showed that in order to estimate the number of IgA producing cells per mm3 of lamina propria with a confidence of 95% that the mean of the sample would not differ by more than 5% from the mean of the population, it would be necessary to count 850-900 microscopic fields. With a confidence of 90% that the two means cited will not differ between them by more than 10%, the number of fields to be counted would lie in the range of 150 to 200. In the second procedure we arbitrarily divided the mucosa into upper, middle and lower segments, identifying and counting the number of cells in each segment. Consistent results for the number of IgA, IgM and IgG-containing cells were obtained by averaging the data of sufficient number of counts of 30 fields: 10 in the upper segment, 10 in the middle segment and 10 in the lower segment. Means obtained by stratified counts of IgA producing cells in 60 microscopic fields, 20 in each segment, differed, in 93% of the samples, by no more than 10% from the mean derived from the counts of 200 successive fields. Stratified sampling also enabled us to detect a segmental variation which had not thus far been quantified. In all cases, it was observed that the numerical concentration of IgA producing cells was greater in the lower region than in the middle zone, while for both IgM and IgG cells the larger numbers occurred in the middle and lower segments. The lowest concentration of IgA, IgM and IgG cells occurred at the top of the villi.