Performance assessment and benchmarking of autologous peripheral blood stem cell collection with two different apheresis devices.

BACKGROUND: Collection of peripheral blood stem cells (PBSCs) for autologous transplantation is a well-established process. As a new generation of leukapheresis (LP) machines has been launched, measures of benchmarking and quality control need to be defined in order to ensure consistent collection performance. OBJECTIVES: The goal of this project was to establish and evaluate a benchmarking system for autologous PBSC collection. METHODS: This retrospective study evaluated PBSC collection data of 198 patients with symptomatic multiple myeloma in first-line therapy who underwent LP in 2013 and 2014 at our institution. Half the patients in 2014 were assigned randomly to undergo LP with the new Terumo BCT Spectra Optia (Terumo BCT, Garching, Germany), while the COBE Spectra (Terumo BCT) was used in all other cases. In 2014, we implemented a previously described formula for predicting daily CD34+ cell collection. As a benchmark, we developed the performance ratio: collected/predicted CD34+ cells. RESULTS: There was no significant difference in the number of collected CD34+ cells, the collection efficiency (collected/processed CD34+ cells) and performance ratio between the two collection devices and between LP procedures in 2013 and 2014. CONCLUSIONS: We present a comprehensive benchmarking tool that is easy to implement, requires minimal expense and allows specific adjustment of LP parameters for optimisation of LP performance. With this approach, we could confirm the equal efficiency of the two compared apheresis systems.

Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents.

BACKGROUND: High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is considered the standard of care for multiple myeloma (MM) patients <65 years. Safety and outcome of ASCT for patients >65 years is currently uncertain, especially since the introduction of novel agents for induction and maintenance therapy. Furthermore, there are no conclusive data available on risk assessment in elderly patients treated with HDT. PATIENTS AND METHODS: We retrospectively analyzed 202 patients ≥60 years with newly diagnosed MM who underwent ASCT at our institution. Patients were stratified by age into three groups (60-64, 65-69 and 70-75 years). For safety assessment, we compared data about hospitalization, hematopoetic reconstitution and early mortality. Remission before and after ASCT was analyzed according to age and application of novel agents. Event-free (EFS) and overall survival (OS) were analyzed to identify impact of age, remission before/after ASCT and maintenance therapy as well as ISS score and cytogenetic aberrations on outcome in elderly patients. RESULTS: The assessment of safety, remission before/after ASCT as well as EFS and OS showed no significant differences between the three groups (median EFS: 60-64 years: 27 months; 65-69 years: 23 months; 70-75 years: 23 months; median OS: not reached). Patients receiving novel agents as part of induction therapy achieved significantly higher nCR + CR rates than patients treated without novel agents. In Cox regression analysis, ISS and cytogenetics as well as remission after ASCT had the highest prognostic impact on EFS and OS. Maintenance therapy was associated with longer EFS in uni- and multivariate analyses. CONCLUSION: ASCT is feasible for selected patients >65 and >70 years without increased mortality. Age at transplantation has no prognostic significance on outcome after ASCT. Novel agents during induction therapy and maintenance therapy improves outcome of older patients eligible for ASCT. ISS and cytogenetic analysis should be carried out routinely for risk assessment.

[Mild bleeding diathesis in a 62-year-old woman with hereditary thrombocytopenia]. / Milde Blutungsneigung bei einer 62-Jährigen mit hereditärer Thrombozytopenie.

A 62-year-old woman presented with severe, isolated thrombocytopenia. Due to the positive family history and normal thrombocyte morphology ANKRD26-associated thrombocytopenia 2 (THC2) was suspected. The diagnosis was confirmed by DNA sequencing. Although this is the first case report on THC2 in Germany, we anticipate that THC2 might be a frequent cause of hereditary thrombocytopenia. A specific therapy was not necessary, but would consist of platelet supplementation.

Lack of CD56 expression on myeloma cells is not a marker for poor prognosis in patients treated by high-dose chemotherapy and is associated with translocation t(11;14).

Lack of CD56 expression was reported to be associated with a poor prognosis in multiple myeloma (MM) patients treated with conventional chemotherapy. Aim of our retrospective study was to analyse whether CD56 expression on MM cells reveals as a prognostic factor in patients treated with high-dose chemotherapy. MM cells of 99 patients prior to treatment with high-dose chemotherapy were analysed for CD56 expression by flow cytometry. Multivariable analysis of event-free survival in these patients showed no statistically significant difference between the CD56(-) (n=28) and the CD56(+) (n=71) group. The lack of CD56 expression on MM cells of these patients correlated significantly with the presence of translocation (11;14) (t(11;14)) (estimated correlation coefficient=0.655 95%, confidence interval (0.481; 0.779)). In summary, our results indicate that lack of CD56 expression on MM cells is not a prognostic marker in patients treated with high-dose chemotherapy, but is associated with t(11;14).

Bone morphogenic protein 6: a member of a novel class of prognostic factors expressed by normal and malignant plasma cells inhibiting proliferation and angiogenesis.

Pathogenesis of multiple myeloma is associated with an aberrant expression of pro-proliferative, pro-angiogenic and bone-metabolism-modifying factors by malignant plasma cells. Given the frequently long time span from diagnosis of early-stage plasma cell dyscrasias to overt myeloma and the mostly low proliferation rate of malignant plasma cells, we hypothesize these to similarly express a novel class of inhibitory factors of potential prognostic relevance. Bone morphogenic proteins (BMPs) represent possible candidates as they inhibit proliferation, stimulate bone formation and have an effect on the survival of cancer patients. We assessed the expression of BMPs and their receptors by Affymetrix DNA microarrays (n=779) including CD138-purified primary myeloma cell samples (n=635) of previously untreated patients. BMP6 is the only BMP expressed by malignant and normal plasma cells. Its expression is significantly lower in proliferating myeloma cells, myeloma cell lines or plasmablasts. BMP6 significantly inhibits the proliferation of myeloma cell lines, survival of primary myeloma cells and in vitro angiogenesis. A high BMP6 expression in primary myeloma cell samples delineates significantly superior overall survival for patients undergoing high-dose chemotherapy independent of conventional prognostic factors (International Staging System (ISS) stage, beta(2) microglobulin).

[Cytomegalovirus infection as a possible factor in the progression of neuroblastoma]. / Die Zytomegalievirusinfektion als möglicher Progressionsfaktor bei der Neuroblastomerkrankung.

BACKGROUND: There is evidence that the infection with human cytomegalovirus is clinically associated with enhanced metastasis and progression of neuroblastoma disease. An in vitro model with HCMV-infected neuroblastoma cells (NB) was used to investigate whether HCMV modulates the metastatic potential of NB. METHODS: The neuroblastoma cell line UKF-NB-4 and its productively and persistently HCMV-infected variant UKF-NB-4AD169 were cocultured with human endothelial cells (EC). The rate of NB adherent to the endothelial monolayer and the rate of transmigrating NB was determined by means of combined reflexion interference contrast/phase contrast microscopy. RESULTS: UKF-NB-4AD169 adhered to and transmigrated through cocultured EC monolayer to a significantly higher extent compared with the non-infected cell line UKF-NB-4. At the cell-to-cell contact sites between UKF-NB-4AD169 and EC the intercellular endothelial contacts loosened resulting in the formation of reversible focal openings in the monolayer. This phenomenon was not observed with UKF-NB-4. The transendothelial migration rate of UKF-NB-4AD169 was therefore significantly higher than that of UKF-NB-4. The formation of focal openings in the endothelial monolayer and the enhanced transmigration rate of UKF-NB-4AD169 was suppressed in the presence of phenantroline, suggesting that HCMV-induced proteinases might be responsible for this phenomenon. CONCLUSION: The results confirm our assumption that HCMV has the ability to modulate functional properties of NB which are essential for the interactions with endothelial cells and thus for metastasation. The clinical relevance of these findings has to be further defined yet by means of prospective studies with HCMV-infected neuroblastoma patients. Proteinase inhibitors could be valuable in the therapeutic treatment of these patients.