Features of extramedullary myeloma relapse: high proliferation, minimal marrow involvement, adverse cytogenetics: a retrospective single-center study of 24 cases

Abstract

Extramedullary (e) relapse in multiple myeloma(MM) has an adverse prognosis, but knowledge concerning biological features and preferred treatment is scarce. We screened the myeloma registry of our institution for eMM relapses and identified 24 cases among 357 patients (pts).Only 8% of eMM relapses occurred after initial therapy, but 54% occurred after third-line or subsequent therapy. Baseline molecular cytogenetics revealed high-risk features in 10 of 19 evaluable patients. Most frequently, eMM presented as soft tissue (67%) and organ involvement (25%) or malignant effusion (12.5%). Incidence of leptomeningeal/CNS involvement was 21%. At eMM relapse, bone marrow infiltration was absent in 46% and low in 21%. Ten eMM biopsies were available showing increased proliferation, i.e., Ki-67 of 67%(range, 30–90%) of all cancer cells. Pts received radiation therapy, dose-intense chemotherapy, novel agents, and allogeneic SCT resulting in an overall response rate of 54%. Median progression-free survival was 2 (95% CI 0.08–3.92) and median overall survival 7 months (95% CI 3.56–10.43), respectively,with only three patients being alive at 12 months from diagnosis. EMM relapse may present at any anatomical site with frequent CNS involvement. Biological features include increased proliferation and low rate of marrow involvement.Prognosis remains poor despite intensive treatment.

Myelomatous Meningitis Evaluated by Multiparameter Flow Cytometry : Report of a Case and Review of the Literature

“…3,10,17 Several observation are in agreement with a possible role of p53 deletions, 4 high nuclear accumulation of the p53 protein, 34 and del (17p13). 10 An interesting report by Gozzetti et al 16 showed the possible involvement of t (11;14), which seems to be associated with standard risk, but also with high risk in the presence of plasma cell leukemia.…”

“…We found that a total number of 187 cases had been reported until 2012. [3][4][5][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] The same case was described in two different instances. 19,23 Therefore, we reviewed review articles and single case reports in order to obtain more information about patients characteristics, the method used to detect plasma cells in the CSF and plasma cell phenotype.…”

“…In addition, Rasche et al reported positivity for CD56 in eight of ten patients with extramedullary relapse of MM, using immunohistochemical assays. 17 Therefore, the role of CD56 down-regulation in favoring the localization of MM plasma cells in the CSF, as well as in other sites, deserves further investigation and more cases should be analyzed by means of flow cytometry not only using samples from the bone marrow, but also measuring CD56 expression on plasma cells obtained from CSF samples.…”

How I treat extramedullary myeloma

“…6 High LDH levels, anemia, thrombocytopenia, nonsecretory MM, and highrisk cytogenetic features are more frequent in patients with de novo EMM than in patients with classic MM. 16,21,22 Interestingly, the combination of high LDH level and high-risk cytogenetic features, parameters found to be more frequent in EMM, has been described to be associated with an ultrahigh risk of early progression or disease-related death in MM patients. 23 Moreover, the frequency of high-risk gene expression profiles (MAF and PR) is found to be higher in EMM patients.…”

Successful treatment with lenalidomide dexamethasone for second relapse of a patient with non-secretory multiple myeloma with extramedullary liver plasmacytomas: A case report

“…Extramedullary plasmacytomas usually show a more aggressive, plasmablastic morphology [6]. High LDH levels, high-risk cytogenetic features, anemia, thrombocytopenia and nonsecretory MM are more frequent in patients with EMM [11][12][13]. Currently, the underlying molecular pathogenesis of the extramedullary spread of PCs is only partially understood.…”