Peripheral blood stem cell mobilisation following bortezomib, lenalidomide and dexamethasone induction for multiple myeloma: a real-world single-centre experience.

BACKGROUND: Bortezomib, lenalidomide and dexamethasone (VRd) is now the standard-of-care induction therapy for newly diagnosed transplant-eligible multiple myeloma patients, replacing bortezomib, cyclophosphamide and dexamethasone (VCD) therapy. Lenalidomide can negatively impact stem cell yield because of its myelosuppressive effects, although studies have shown that the latter can be overcome with the use of cyclophosphamide for peripheral blood stem cell (PBSC) mobilisation. AIMS AND METHODS: To investigate whether lenalidomide impacts on PBSC mobilisation and to evaluate the optimal mobilisation strategy post VRd induction, we performed a retrospective review of 56 myeloma patients at a single centre who had PBSC mobilisation between January 2019 and March 2021 and compared three cohorts: (i) VCD induction; mobilisation with granulocyte colony-stimulating factor (G-CSF) alone (n = 23); (ii) four cycles VRd induction; mobilisation with G-CSF and cyclophosphamide (G-CSF + Cyclo) (n = 20); and (iii) three cycles VRd induction; mobilisation with G-CSF alone (n = 13). RESULTS: There was no difference in the mean total CD34 count between VCD and VRd patients who had G-CSF mobilisation (6.27 × 106 /kg vs 5.50 × 106 /kg, P > 0.99). VRd patients mobilised with G-CSF + Cyclo achieved higher mean total CD34 counts compared with G-CSF alone (8.89 × 106 /kg vs 5.50 × 106 /kg, P = 0.04). The majority of VRd patients who had G-CSF + Cyclo (19 of 20; 95%) collected sufficient cells for two or more autologous stem cell transplants (ASCTs), regardless of whether this was required, compared with eight of 13 (62%) VRd patients who had G-CSF alone. CONCLUSION: We conclude that successful PBSC mobilisation for at least one ASCT is possible after three cycles of VRd induction using G-CSF alone. The upfront use of a cyclophosphamide-based mobilisation strategy has a role in patients who have had VRd induction, where the aim is to collect enough stem cells for two or more ASCTs.

The impact of surgical sequence on outcome rates of artificial urinary sphincter implantation: comparative effectiveness of primary, secondary and repeat implantation.

PURPOSE: To determine whether salvage artificial urinary sphincter (AUS) implantation after prior incontinence surgery achieves outcomes comparable to primary AUS implantation. METHODS: We retrospectively evaluated data of patients undergoing AUS implantation from 2009 to 2014. Functional outcome was objectified by 1-h stress pad test, uroflowmetry, post-void residual urine measurement, clinical examination, and chart review. Complications were categorized according to Clavien-Dindo classification system. Kaplan-Meier analysis determined explantation-free survival. RESULTS: A total of 235 patients were included of whom 165 (70.2%) underwent primary AUS. In 70 patients, salvage incontinence surgery was performed, with 24 (10.2%) patients undergoing AUS reimplantation after prior AUS surgery (repeat AUS) and 46 (19.6%) patients undergoing AUS surgery after any other type of incontinence surgery (secondary AUS). There were no significant differences in rates of continence among primary AUS and repeat AUS patients. Patients undergoing secondary AUS had significantly better continence rates than primary and repeat AUS patients. Three-year explantation-free survival rates after AUS insertion were 82.3% (primary AUS), 78.6% (repeat AUS) and 81.5% (secondary AUS). There were no differences in complication rates among the groups. CONCLUSION: AUS is a safe option in the treatment of severe incontinence even after prior AUS or any other prior incontinence surgery and can still achieve satisfactory outcomes as salvage treatment.

Comparison of biosimilar filgrastim with originator filgrastim for peripheral blood stem cell mobilization and engraftment in patients with multiple myeloma undergoing autologous stem cell transplantation.

BACKGROUND: Nivestim is a biosimilar approved for the same indications as Neupogen including the mobilization of autologous peripheral blood stem cells (PBSCs). The clinical efficacy and safety of Nivestim for this use have not been formally assessed in clinical trials. STUDY DESIGN AND METHODS: In our retrospective single-center study we compared variables of PBSC mobilization and engraftment of 60 patients mobilized with Nivestim to that of 38 patients mobilized with Neupogen. RESULTS: We found no difference between Nivestim and Neupogen in peripheral blood CD34+ at first leukapheresis (47 × 10(6) cells/L vs. 60 × 10(6) cells/L, p = 0.48) nor the total CD34+ collected (5.37 × 10(6)/kg vs. 4.59 × 10(6) /kg, p = 0.22). However, a difference in the median number of leukapheresis procedures (one vs. two, p = 0.0007) was observed. Eighty-one patients (51 Nivestim and 30 Neupogen mobilized) went on to transplantation. Median time to neutrophil engraftment (15 days vs. 13.5 days, p = 0.09) and platelet (PLT) engraftment (20 days vs. 18 days, p = 0.01) was longer in the Nivestim group. The significant delay in PLT engraftment did not, however, translate to increased PLT transfusions (two vs. three, p = 0.2) or impact significantly on hospitalization time for admissions within 30 days posttransplant (20 days vs. 18 days, p = .17). CONCLUSION: Nivestim is as effective as Neupogen for PBSC mobilization; however, its use was associated with a delay in PLT recovery. A prospective study should be conducted to confirm our findings.

Primary synovial sarcoma of the kidney with rhabdoid features.

Synovial sarcoma is a soft tissue sarcoma with clearly defined histologic, immunophenotypic, and molecular features. It occurs predominantly in the extremities of young adults but has been reported in many other anatomic sites. Histologically, it is classified as biphasic, monophasic, and poorly differentiated. The latter category, which includes tumors with a rhabdoid morphology, has been associated with a more aggressive behavior. Generally, the biphasic variant does not pose any diagnostic problem because of its typical histologic appearance; in contrast, the monophasic and poorly differentiated variants may represent a diagnostic challenge because their microscopic features can be confused with those of other spindle cell tumors with rhabdoid features. The application of molecular techniques, such as reverse transcriptase polymerase chain reaction to detect the fusion transcript associated with the characteristic t(X;18) translocation of synovial sarcoma, has enabled the confirmation of this diagnosis, even in cases of unusual localization, such as the one we present here.

High-Throughput Microdissection for Next-Generation Sequencing.

Precision medicine promises to enhance patient treatment through the use of emerging molecular technologies, including genomics, transcriptomics, and proteomics. However, current tools in surgical pathology lack the capability to efficiently isolate specific cell populations in complex tissues/tumors, which can confound molecular results. Expression microdissection (xMD) is an immuno-based cell/subcellular isolation tool that procures targets of interest from a cytological or histological specimen. In this study, we demonstrate the accuracy and precision of xMD by rapidly isolating immunostained targets, including cytokeratin AE1/AE3, p53, and estrogen receptor (ER) positive cells and nuclei from tissue sections. Other targets procured included green fluorescent protein (GFP) expressing fibroblasts, in situ hybridization positive Epstein-Barr virus nuclei, and silver stained fungi. In order to assess the effect on molecular data, xMD was utilized to isolate specific targets from a mixed population of cells where the targets constituted only 5% of the sample. Target enrichment from this admixed cell population prior to next-generation sequencing (NGS) produced a minimum 13-fold increase in mutation allele frequency detection. These data suggest a role for xMD in a wide range of molecular pathology studies, as well as in the clinical workflow for samples where tumor cell enrichment is needed, or for those with a relative paucity of target cells.