Multiple myeloma patients in long-term complete response after autologous stem cell transplantation express a particular immune signature with potential prognostic implication

Abstract

The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC). Heavy/light chains (HLC) were quantified by nephelometry. The percentage of CD4 T-cells was lower in patients, whereas an increment in the percentage of CD4 and CD8 effector memory T-cells was associated with the LTCR. Regulatory T-cells and NK-cells were similar in both groups but a particular redistribution of inhibitory and activating receptors in NK-cells were found in patients. Regarding B-cells, an increase in naïve cells and a corresponding reduction in marginal zone-like and class-switched memory B-cells was observed. The HLC values were normal. Our results suggest that LTCR-MM patients express a particular immune signature, which probably reflects a 'high quality' immune reconstitution that could exert a competent anti-tumor immunological surveillance along with a recovery of the humoral immunity.

Mortality in Elderly Waiting-List Patients Versus Age-Matched Kidney Transplant Recipients: Where is the Risk?

“…With ageing, an interaction between great CV comorbidity and infections and neoplastic processes within the framework of immunosuppressive therapy seems likely, leading to excessive post-transplant mortality [8, 42-44]. In addition, the risk of death in older KT recipients increases with increased comorbidity during the first post-transplant year [39, 45]. Finally, older KT recipients are susceptible to cognitive impairment, poor functional status and frailty, increasing hospital readmission and mortality risk [46-50].…”

The serum heavy/light chain immunoassay: A valuable tool for sensitive paraprotein assessment, risk, and disease monitoring in monoclonal gammopathies

“…Before these results will be available, prior [5][6][7][8][10][11][12][13][14]18,27,28 and our data should provide notable information on this assay and should excite relevant HLC-questions in larger patient cohorts in future clinical trials.…”

“…We here analysed 147 consecutive patients with monoclonal gammopathies to evaluate the potential benefit of the HLC assay for future clinical routine. Due to our inclusion of IgG‐ and IgA‐MM, WM, SMM, and MGUS patients, both newly diagnosed and those at least 6 months after diagnosis, we did not have an entirely uniform patient clientele . Our aims were, however, slightly different from these previous analyses, namely to assess the exact HLC correlation with other MM serum parameters (Table and ), to compare both HLC and SFLC assays, whereby the HLC assay showed more pathological samples than via SFLC assay alone (Figure B), to find best HLC κ/λ‐ratio cutoffs for PFS, as these are not consistent in the literature (Table ) and to evaluate the value of HLC κ/λ‐ratios in MGUS and SMM patients (Tables and ).…”

“…All potential clinical utilizations assessed here need to be confirmed in future studies, within clinical trials, with larger patient numbers, uniform treatment and in different monoclonal gammopathy subgroups before the HLC assay will be used for routine diagnostics. Before these results will be available, prior and our data should provide notable information on this assay and should excite relevant HLC‐questions in larger patient cohorts in future clinical trials.…”

“…Due to our inclusion of IgG-and IgA-MM, WM, SMM, and MGUS patients, both newly diagnosed and those at least 6 months after diagnosis, we did not have an entirely uniform patient clientele. 5,8,10,27,28 Our aims were, however, slightly different from these previous analyses, namely to assess the exact HLC correlation with other MM serum parameters (Table 1 and 2), to compare both HLC and SFLC assays, whereby the HLC assay showed more pathological samples than via SFLC assay alone ( Figure 1B), to find best HLC κ/λ-ratio cutoffs for PFS, as these are not consistent in the literature (Table 3) and to evaluate the value of HLC κ/λ-ratios in MGUS and SMM patients (Tables S2 and S3). Our results verified a close association between both HLC values and HLC κ/λ-ratios with standard MM diagnostics, as well as with disease stage, remission status and PFS.…”