Impact of a mental training program for pediatric cancer patients after allogeneic hematopoietic stem cell transplantation or high-dose chemotherapy - Results of a randomized controlled trial.

OBJECTIVES: Hematopoietic stem cell transplantation (HSCT) or intensive chemotherapy for the treatment of malignant diseases is a highly distressing experience. The affected person's resilience is crucial to coping with this challenging experience. Experience with resilience-enhancing interventions in children and young adults during cancer therapy is scarce. The major objective of this work was developing and evaluating an effective psycho-oncological mental training that complements the standard psychosocial care. METHODS: In this prospective, randomized single-center study, a total of 30 patients (12 to 22 years of age) who underwent HSCT or high-dose chemotherapy received either the standard psychosocial care (control group [CG]) or additionally underwent a novel and specifically developed resilience-enhancing 14-session mental training (therapy group [TG]). The patients were observed over an 8-month period and were screened for distress, thyroid, and immune function parameters, as well as generalized anxiety, affect, and sports orientation. RESULTS: Patients of the TG showed significantly greater improvements in all assessed mental aspects, including anxiety, affect, competitiveness, win orientation, goal orientation, self-optimization, self-blocking, and loss of focus, as well as cortisol levels within 8 months, as opposed to patients of the CG (effect size range ξ: 0.74-1.00). SIGNIFICANCE OF RESULTS: Patients who underwent the mental training displayed less anxiety, better affect, and improved mental performance with less self-blocking. This resulted in improved goal orientation, competitiveness, self-optimization, and focus when compared to the CG patients. However, larger prospective trials are necessary to substantiate these findings.

Hypofibrinolysis in pediatric patients with veno-occlusive disease in hematopoietic stem cell transplantation.

PURPOSE: Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplantation (HSCT) with a high incidence in pediatric patients. This study aimed to detect signs of hypofibrinolysis using thrombelastography. METHODS: In this prospective single-center study, thrombelastographic measurements (EX and TPA tests) were taken during HSCT to detect signs of impaired coagulation, clot formation, or hypofibrinolysis. RESULTS: Of 51 patients undergoing allogeneic and autologous HSCT, five (9.8%) developed VOD and received defibrotide treatment. Thrombelastography measurements were also obtained from 55 healthy children as a control group. The results show that clot lysis was prolonged in VOD patients compared to other HSCT patients and control group (lysis time, TPA test: day + 14 to + 21: VOD: 330 ± 67 s vs. HSCT: 246 ± 53 s; p = 0.0106; control: 234 ± 50 s; control vs. VOD: p = 0.0299). The maximum lysis was reduced in HSCT patients compared to controls (EX test: control: 8.3 ± 3.2%; HSCT: day 0 to + 6: 5.3 ± 2.6%, p < 0.0001; day + 7 to + 13: 3.9 ± 2.1%, p < 0.0001; day + 14 to d + 21: 4.1 ± 2.3%, p < 0.0001). CONCLUSION: These results suggest that HSCT patients exhibit reduced fibrinolytic capacities and patients diagnosed with VOD show signs of hypofibrinolysis. This prospective study shows that fibrinolysis can be assessed in a rapid and accessible way via thrombelastography. Thrombelastography might be a parameter to support the diagnosis of a VOD and to serve as a follow-up parameter after the diagnosis of a VOD.

Design and operation of a continuous integrated monoclonal antibody production process.

The realization of an end-to-end integrated continuous lab-scale process for monoclonal antibody manufacturing is described. For this, a continuous cultivation with filter-based cell-retention, a continuous two column capture process, a virus inactivation step, a semi-continuous polishing step (twin-column MCSGP), and a batch-wise flow-through polishing step were integrated and operated together. In each unit, the implementation of internal recycle loops allows to improve the performance: (a) in the bioreactor, to simultaneously increase the cell density and volumetric productivity, (b) in the capture process, to achieve improved capacity utilization at high productivity and yield, and (c) in the MCSGP process, to overcome the purity-yield trade-off of classical batch-wise bind-elute polishing steps. Furthermore, the design principles, which allow the direct connection of these steps, some at steady state and some at cyclic steady state, as well as straight-through processing, are discussed. The setup was operated for the continuous production of a commercial monoclonal antibody, resulting in stable operation and uniform product quality over the 17 cycles of the end-to-end integration. The steady-state operation was fully characterized by analyzing at the outlet of each unit at steady state the product titer as well as the process (HCP, DNA, leached Protein A) and product (aggregates, fragments) related impurities. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1303-1313, 2017.

Biotin-independent strains of Escherichia coli for enhanced streptavidin production.

Biotin is an archetypal vitamin used as cofactor for carboxylation reactions found in all forms of life. However, biotin biosynthesis is an elaborate multi-enzymatic process and metabolically costly. Moreover, many industrially relevant organisms are incapable of biotin synthesis resulting in the requirement to supplement defined media. Here we describe the creation of biotin-independent strains of Escherichia coli and Corynebacterium glutamicum through installation of an optimized malonyl-CoA bypass, which re-routes natural fatty acid synthesis, rendering the previously essential vitamin completely obsolete. We utilize biotin-independent E. coli for the production of the high-value protein streptavidin which was hitherto restricted because of toxic effects due to biotin depletion. The engineered strain revealed significantly improved streptavidin production resulting in the highest titers and productivities reported for this protein to date.