The impact of cytogenetics on duration of response and overall survival in patients with relapsed multiple myeloma (long-term follow-up results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial.

The Myeloma X trial (ISCRTN60123120) registered patients with relapsed multiple myeloma. Participants were randomised between salvage autologous stem cell transplantation (ASCT) or weekly cyclophosphamide following re‐induction therapy. Cytogenetic analysis performed at trial registration defined t(4;14), t(14;16) and del(17p) as high‐risk. The effect of cytogenetics on time to progression (TTP) and overall survival was investigated. At 76 months median follow‐up, ASCT improved TTP compared to cyclophosphamide (19 months (95% confidence interval [95% CI] 16–26) vs. 11 months (9–12), hazard ratio [HR]: 0·40, 95% CI: 0·29–0·56, P < 0·001), on which the presence of any single high‐risk lesion had a detrimental impact [likelihood ratio test (LRT): P = 0·011]. ASCT also improved OS [67 months (95% CI 59‐not reached) vs. 55 months (44–67), HR: 0·64, 95% CI: 0·42–0·99, P = 0·0435], with evidence of a detrimental impact with MYC rearrangement (LRT: P = 0·021). Twenty‐one (24·7%) cyclophosphamide patients received an ASCT post‐trial, median OS was not reached (95% CI: 39‐not reached) for these participants compared to 31 months (22–39), in those who did not receive a post‐trial ASCT. The analysis further supports the benefit of salvage ASCT, which may still be beneficial after second relapse in surviving patients. There is evidence that this benefit reduces in cytogenetic high‐risk patients, highlighting the need for targeted study in this patient group

Teleost fish mount complex clonal IgM and IgT responses in spleen upon systemic viral infection

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Older Human B Cells and Antibodies

B cells have a number of different roles in the immune response. Their excellent antigen presentation potential can contribute to the activation of other cells of the immune system, and evidence is emerging that specialized subsets of these cells, that may be increased with age, can influence the cell-mediated immune system in antitumor responses. They can also regulate immune responses, to avoid autoreactivity and excessive inflammation. Deficiencies in regulatory B cells may be beneficial in cancer but will only exacerbate the inflammatory environment that is a hallmark of aging. The B cell role as antibody producers is particularly important, since antibodies perform numerous different functions in different environments. Although studying tissue responses in humans is not as easy as in mice, we do know that certain classes of antibodies are more suited to protecting the mucosal tissues (IgA) or responding to T-independent bacterial polysaccharide antigens (IgG2) so we can make some inference with respect to tissue-specific immunity from a study of peripheral blood. We can also make inferences about changes in B cell development with age by looking at the repertoire of different B cell populations to see how age affects the selection events that would normally occur to avoid autoreactivity, or increase specificity, to antigen