Median OS for the group with Ig recovery at this landmark time point was significantly longer than the median OS for the 81 patients without Ig recovery

Median OS for the group with Ig recovery at this landmark time point was significantly longer than the median OS for the 81 patients without Ig recovery. vs. 7.3 years; Hazard Ratio: 0.45, 95%Confidence Interval: 0.270.74;P=0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: nine months and one year. In conclusion, the recovery of polyclonal immunoglobulins one year after autologous transplantation in myeloma patients is an impartial long-term predictor marker for progression and survival. == Introduction == High-dose therapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for young, newly diagnosed multiple myeloma (MM) patients. It produces high rates of complete remission, and prolonged progression-free survival (PFS) and overall survival (OS).13However, MM is still an incurable disease, with a high rate of relapse or progression after ASCT.4In recent years, several prognostic factors have been identified that predict outcomes after ASCT, such as treatment response, persistence (or not) of minimal residual disease (MRD) or cytogenetic abnormalities. In addition, researchers have shown an increased interest in immune reconstitution after this procedure, based on the premise that an early, strong and sustained recovery of the immune system could help eliminate residual myeloma plasma cells (PCs), thereby improving the final outcome. In fact, several studies have reported positive impacts of early lymphocyte recovery, the presence of oligoclonal bands or an early reconstitution of natural killer (NK) cells on survival.58 Most MM patients (85%90%) exhibit immunoparesis at the time of diagnosis.9This condition is defined as a reduction in the levels of polyclonal or uninvolved immunoglobulins (Igs).10Several mechanisms are thought to be involved in immunoparesis, such as impaired B-cell differentiation related to humoral and cellular immune dysfunction, and the reduction of the quantity of B lymphocytes due to cytokines produced by myeloma cells (TGF-).11Moreover, it seems that this B-cell suppression is reversible and inversely correlated with disease stage.12In fact, the presence of immunoparesis in smoldering myeloma is considered to be a prognostic marker of progression to symptomatic myeloma,13and is also associated with adverse outcome in newly diagnosed symptomatic myeloma patients.9In CP-809101 the ASCT CP-809101 setting, after high doses of melphalan and the infusion of stem cells, an immune reconstitution is expected, including the reappearance of functional B lymphocytes and, thereby, the recovery of polyclonal Igs.14On this basis, we hypothesized that persistence of immunoparesis after ASCT may predict worse progression or CP-809101 survival in patients with MM, similarly to the other, aforementioned markers of immune dysfunction. The primary goal of this study was to determine whether the recovery of polyclonal Igs after ASCT is usually of prognostic value in a cohort of patients with MM. We show that this immunoglobulin KLRK1 (Ig) recovery one year after ASCT is an impartial prognostic factor associated with longer CP-809101 PFS and OS in MM patients undergoing this CP-809101 procedure. == Methods == We retrospectively evaluated patients from our region diagnosed with symptomatic MM, according to the 2003 criteria, who consecutively underwent ASCT at either of two referral centers, the University Hospitals of Salamanca and of Len, Spain, between 1993 and 2014. Clinical and biological data were collected by searching the medical records and databases of each hospital. Serum immunoglobulin levels (IgG, IgA and IgM) were measured by nephelometry. Immunoparesis was defined as a more than 25% decrease.

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