SummaryProteasome inhibitors (PI) and immunomodulatory agents (IMIDs) have improved the overall survival (OS) of patients with multiple myeloma (MM), but concerns have been raised about increased incidence of extramedullary disease (EMD) after the combined use of PIs and IMIDs for upfront therapy. We evaluated whether the addition of lenalidomide to bortezomib-based front-line regimens precipitated earlier development of EMD. We reviewed the charts of 117 MM patients (median follow-up from diagnosis 6Á1 years; range 0Á1-10Á2 years) enrolled in eight clinical trials of first-line treatment with bortezomib-based regimens, with or without lenalidomide. We assessed development of EMD as extraosseous (distant from bone) or osseous (originating from bone) plasmacytomas. The primary endpoint was time from diagnosis until development of EMD, based on imaging, biopsy and/or physical examination. Any form of EMD at progression was observed in 40 (34Á2%) patients, including 21 (18%) osseous, 8 (7%) extraosseous and 11 (9%) both osseous and extraosseous. Median OS was 0Á9 years (range 0Á1-4Á8 years) after extraosseous EMD development. Sensitivity analyses with follow-up times truncated at 5 years detected no statistically significant difference in rates of any EMD form between the two groups (P > 0Á2 for each comparison). Therefore, we observed no evidence that bortezomib-lenalidomide-based front-line therapy precipitates earlier EMD.

Background and Objectives  G‐CSF‐mobilized peripheral blood stem cells have long replaced marrow as the major source for allogeneic transplants. Conclusive evidence questioning the long‐term safety of G‐CSF for donors has not been provided, but the cumulative number of followed donors remains insufficient to rule out rare adverse events. A long‐term active follow‐up study of G‐CSF‐mobilized healthy volunteer donors was therefore performed. Patients and Methods  Two hundred and three successive donors were evaluated pre‐apheresis, subjected to G‐CSF‐mobilization/apheresis, and actively followed for 5 years by the same physicians and laboratories. Follow‐up laboratory work included standard biochemical/haematological tests and T‐cell phenotyping. Results  Donor epidemiology was typical for reported stem cell donor cohorts. Acute adverse effects of G‐CSF and apheresis were mild and transient, consistent with the previous reports. Mean circulating CD34+ cells after nine doses of G‐CSF were 124 per μl. Other biochemical/haematological parameters were also altered, consistent with G‐CSF treatment. Spleen enlargement was modest. At first follow‐up, all clinical and laboratory parameters had normalized. Leucocyte/lymphocyte counts and CD4/CD8 ratios were the same as during premobilization work‐up and remained unchanged throughout. A single severe but likely unrelated adverse event, a case of papillary thyroid carcinoma, was reported. Conclusion  The studies add an observation time of almost 500 donor years to the growing body of evidence of the long‐term safety of G‐CSF for allogeneic donor stem cell mobilization.

Summary Extramedullary disease (EMD), defined as an infiltrate of clonal plasma cells at an anatomic site distant from the bone marrow, is an uncommon manifestation of multiple myeloma. Six hundred and sixty-three consecutive patients with multiple myeloma who underwent stem cell transplantation between January 2005 and December 2011 were assessed for the presence of EMD. A cohort of 55 patients with biopsy-proven EMD was identified, comprising 8.3% of the total study population. EMD was present at the time of diagnosis in 14.5% of cases and at the time of relapse in 76% of patients. The most common EMD presentations at relapse were liver involvement and pleural effusions. EMD specimens had high expression of CD44 (92%) and moderate expression of CXCR4. The median overall survival from time of myeloma diagnosis was 4.1 years (95% confidence interval: 3.1, 5.1) and the median overall survival from time of EMD diagnosis was 1.3 years (95% confidence interval: 0.8, 2.3). This report demonstrates that the incidence of EMD has not increased with the introduction of novel agents and stem cell transplantation. The most common EMD presentations in the relapsed setting were liver and pleural fluid. The presence of CD44 and CXCR4 expression may represent new markers of EMD that warrant further investigation.