Background: The optimum number of CD34+ cells to be reinfused in patients undergoing peripheral blood stem cell (PBSC) transplantation (PBSCT) after high-dose chemotherapy is still unknown.
Patients ...and Methods: Hematologic reconstitution was analyzed with respect to the number of CD34+ cells reinfused in 768 patients with advanced MM or AL-amyloidosis treated by PBSCT between 06/1992 and 06/2004. 539 transplantations were performed upfront and 229 transplantations after relapse. Endpoints of the study were the number of days from PBSCT until neutrophil recovery (>1.0x10e9/L), and platelet recovery (>20x10e9/L and >50x10e9/L). A multivariable analysis was performed using Cox proportional hazards regression to model the dependence of neutrophil and platelet recovery on CD34+ cell dose reinfusion (included as continuous variable), age at PBSCT, number of previous regimens, number of cycles with alkylating agents, response status prior to PBSCT (CR or not), CD34+ enrichment, total body irradiation and previous partial irradiation.
Results: The number of CD34+ cells reinfused was the only factor being statistically significant for neutrophil as well as platelet recovery (p<0.001). In view of previously reported cut-offs, three groups were defined (low: <=2.5x10e6; high: >8x10e6 CD34+ cells/kg; and intermediate). In the patients treated by PBSCT up-front, the 100 patients of the high-group experienced a shorter median time until neutrophil recovery (low/intermediate/high CD34+:14/14/12 days), platelet recovery >20x10e9 (low/intermediate/high CD34+: 11/11/9 days), and platelet recovery >50x10e9/L (low/intermediate/high CD34+: 13/13/11 days) compared to patients of the intermediate and low groups. These 100 patients required less platelet and red blood cell transfusions, experienced a shorter hospitalization, had fewer days with antibiotic and antimycotic treatment, and required less partial and total parenteral nutrition. In the patients treated by PBSCT at relapse, the 29 patients of the high-group also experienced a shorter median time until neutrophil (low/intermediate/high CD34+: 13/14/12 days), platelet recovery >20x10e9 (low/intermediate/high CD34+: 12/11/9 days), and platelet recovery >50x10e9/L (low/intermediate/high CD34+: 15/14/11 days) compared to patients of the intermediate and low groups. The advantages for the 29 high group relapse-patients regarding the supportive care after PBSC transplantation were similar to those observed in the 100 upfront-patients: shorter duration of hospitalization, fewer days of antibiotic and antimycotic treatment, fewer days of partial parenteral nutrition and total parenteral nutrition, less platelet and red blood cell transfusions.
Conclusion: The number of CD34+ cells reinfused significantly influences time until neutrophil as well as platelet recovery. Comparison of groups suggests that reinfusion of more than 8x10e6 CD34+ cells/kg after high-dose chemotherapy for advanced MM or AL-amlyoidosis shortens hematopoietic reconstitution, reduces platelet and red blood cell transfusions, and reduces days of hospitalization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Suppression of polyclonal immunoglobulin (Ig) synthesis is one feature of multiple myeloma (MM). To evaluate if recovery of polyclonal Ig synthesis after autologous stem cell transplantation (ABSCT) ...influences prognosis, we have retrospectively analyzed the prognostic value of clinical and laboratory variables of 348 multiple myeloma patients who underwent their first autologous stem cell transplantation between 06.1992 and 10.2002 at the University Hospital of Heidelberg. The median follow-up was 34 months (range, 3 to 136 months). The median number of chemotherapy courses prior to first ABSCT was 5 (range, 3 to 30). Twenty-two of 348 patients underwent altogether three ABSCTs (including 18 patients with tandem transplantations), 141 had two ABSCTs (including 87 tandem transplantations) and 29 patients were treated with allogeneic transplantation as second line treatment. Recovery of polyclonal Ig synthesis was studied by serumelectrophoresis on day 100 after first ABSCT (±30 days). Full polyclonal Ig recovery was observed in 93 of 348 patients (28%), partial recovery (reduced polyclonal Ig, no monoclonal Ig) in 58 (17%), no recovery (almost no polyclonal Ig and no monoclonal Ig) in 16 (5%), polyclonal Ig recovery associated with monoclonal Ig in 95 (27%) and monoclonal Ig without polyclonal Ig in 72 patients (21%) (data missing in 14 patients (4%)). On multivariate analysis (333 patients), using Cox proportional hazards regression model stratified with respect to tandem transplantation, superior event-free survival was observed with recovery of polyclonal Ig synthesis, low beta2-microglobulin at diagnosis (<2.5mg/L) and a high haemoglobin at diagnosis, whereas MM type IgA and a high number of chemotherapy courses prior to first ABSCT were identified as adverse prognostic factors. Regarding polyclonal recovery, patients with polyclonal Ig recovery associated with monoclonal Ig had a superior event-free survival compared to patients with only monoclonal Ig without any polyclonal Ig recovery. Overall survival was superior in patients with a low β2-microglobulin at diagnosis (<2.5mg/L) and a high haemoglobin at diagnosis, and worse in patients with a high number of chemotherapy courses prior to first ABSCT. We conclude that any recovery of polyclonal Ig synthesis even when associated with monoclonal Ig, improves event-free survival, and therefore can be used as a predictor of prognosis in the follow-up of multiple myeloma patients who underwent ABSCT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In a prospective multicenter study of coping, subjective well-being and objective course of the disease we recruited patients with life-threatening cardiac arrhythmias awaiting the implantation of a ...cardioverter defibrillator. All patients received a semistructured interview and a number of well validated self-assessment questionnaires. In addition, detailed cardiological findings were documented. The present paper describes the study rationale and design as well as the main study hypotheses. In addition, we present representativity data for the inclusion sample and cross-sectional psychometric findings obtained before implantation of the device. The study sample consists of 286 patients with severe ventricular arrhythmias and is almost representative for all ICD recipients in the participating centers and ICD recipients in general. Despite their severe physical impairment, patients only showed moderate levels of psychological abnormalities. Only patients with severe heart failure or a history of repeated resuscitations showed elevated rates of anxiety or depression. However, there were relevant associations among the self-rating scales: Patients with abnormal anxiety or depression scores reported significantly elevated levels of physical complaints and depressive coping. They also showed low social support and an impaired quality of life. These cross-sectional findings add to the international literature on coping and well-being of patients with malignant cardiac arrhythmias. On the background of earlier research findings and clinical experience our results show high plausibility. Prospective changes over time in the different dimensions of psychosocial adjustment and their prognostic power for future quality of life and arrhythmic events will be reported separately.
Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder. Mutations and polymorphisms of the FVII gene were characterized in more than 40 unrelated patients with FVII deficiency. ...Among the 29 different mutations, the most frequent were Ala294 Val, Ala294Val;404delC, IVS7+7, and Val281 Phe. Four novel mutations (IVS2+1G>C, Arg247 Cys, Glu265 Lys, Asp343 His) were detected. The relationships between genotypes of mutations and polymorphisms of the FVII gene, FVII deficiency, and clinical phenotype were investigated. Homozygosity of the Phe4 Leu, IVS4+1G>A, Cys135 Arg, Ala244 Val, and Ala294 Val;404delC and the double heterozygosity of Tyr68 Cys / IVS3-1G>A, Val252 Met / IVS2+5G>T, Val281 Phe / Cys135 Arg, Ala294 Val / Val281 Phe, Ala294 Val;404delC / Val281Phe, Ala294 Val;404delC / Arg152 stop, Ala294Val;404delC / Gln(-35) stop, Ala294 Val / Val252 Met, Ala294 Val / Gly156 Asp, and Thr359 Met / Asp242 His were related to clinical symptoms. Double heterozygotes for Arg247 Cys / IVS2+1G>C, Ala206 Thr / Pro303 Arg, Leu(-20) Pro / Val252 Met as well as IVS7+7 /Ala294 Val, IVS7+7 /Ala206 Thr, and IVS7+7 / Met298 Ile were asymptomatic. The clinical symptomatology is rather poor in correlation with the FVII activity. Concerning the clinical phanotype, a correlation seems to exist between specific mutations and clinical symptoms.
The partial synthesis of 54 derivatives of thiangazole A (1a), a new polythiazoline antibiotic from Polyangium spec. (myxobacteria), is described. Derivatives with chemical modification of the ...carboxamide group in the oxazole region were prepared either by N‐alkylation to amides 5–14 or by methanolysis to ester 15, and its transformation products 16, 19, 20. Oxidation of the C‐5 methyl group of 1a with molecular oxygen led to the hydroxymethyl derivative 21, and two by‐products lacking the C‐5 methyl group (22), or the entire oxazole ring (23). Key intermediate for analogues with modifications in the styryl region is the aldehyde 27, obtained by direct cleavage of the C‐21/C‐22 double bond. 27 was transformed into the oximes 37–42 and by Wittig reaction to (21Z)‐thiangazole (43) and analogues 44–46 with proton and alkyl residues replacing phenyl. 21,22‐Didehydrothiangazole (50) was synthesized in a multi‐step reaction from 27 via the 20‐alkinyl intermediate 49. The insecticidal activities and inhibition of the respiratory chain (complex I) by the thiangazole analogues were determined and compared with the natural product.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: We analyzed the hematopoietic reconstitution and outcome of 508 patients with multiple myeloma (MM) with respect to the number of CD34 super(+) cells reinfused at our center. Patients and ...methods: Each cohort of 390 patients (unselected CD34 super(+) cell transplant) and 118 patients (CD34 super(+) selected transplant) was divided into four subgroups. Among the 390 transplantations, 86 patients received a high dose (HD super(-)) of greater than or equal to 6.50 x 10 super(6) unselected CD34 super(+) cells/kg, 116 patients a low dose (LD super(-)) of <3.00 x 10 super(6) CD34 super(+) cells/kg. Among the patients treated with CD34 super(+) selected PBSC, 34 received greater than or equal to 6.50 x 10 super(6) CD34 super(+) cells/kg (HD super(+)) and 16 <3.00 x 10 super(6) CD34 super(+) cells/kg (LD super(+)). Results: HD super(-) patients experienced a reduced median time to leukocyte (13 d vs. 14 d) (P < 0.001) and platelet reconstitution >20 x 10 super(9)/L (10 d vs. 12 d) (P < 0.001). Similarly, HD super(+) showed a reduced median time to leukocyte (12 d vs. 15 d) (P < 0.001) and platelet recovery >20 x 10 super(9)/L (10 d vs. 11 d) (P = 0.058). CD34 super(+) cell-dose was significant for long-term platelet recovery at day 360 (unselected transplant P = 0.015, selected transplant P = 0.023). Number of transplanted CD34 super(+) cells had no significant impact on transplant related mortality, overall survival or CR/PR rates within 100 d. In terms of supportive care the differences of high-/low-dose grafts were minimal. Conclusions: These results confirm that high doses of CD34 super(+) PBSC shorten hematopoietic reconstitution and reduce hospitalization. Nevertheless secure engraftment results from transplantation of 2.00-3.00 x 10 super(6) CD34 super(+) cells/kg. As 60% of our pretreated patients are able to collect greater than or equal to 5.00 x 10 super(6) CD34 super(+) cells/kg within a single leukapheresis, division into two or more freezing bags allows safe tandem transplantation in the majority of MM patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
With the recent COP 21 declaration many countries have dedicated themselves to a clear path towards decarbonization. This requires major installation of wind and solar power. However, these only ...provide intermittent electricity. Thus, balance power has to be provided, ideally from renewable resources. Currently only biomass seems to be available in large enough quantity to provide significant balancing power. A wide range of biomass feedstocks can be made available for power generation for example via anaerobic digestion or thermo-chemical gasification. However, resources are still limited. Hence, in order to maximize its potential the biomass has to be used at the highest possible efficiency. Electrochemical conversion, especially in SOFC, in general offers very high efficiency. However, also in SOFC systems the choice of the optimal system design and operating parameters can make a big difference.
The presented work investigates utilization of biogas and syngas from biomass gasification in different system designs. This is done using a thermodynamic SOFC model built in Aspen Plus, which has been validated against literature data. A comparison to cell and stack performance of the well known manufacturers Fuel Cell Energy and Forschungszentrum Jülich is presented. It is shown that at identical operating conditions the model shows slightly worse performance than the real stacks.
With the model, the influence of different fuel pre-treatment and pre-reforming options are compared at a fixed stack size. Furthermore the effect of anode offgas recirculation, as well as the choice of fuel utilization, oxidant, operating temperature and pressure are investigated. During the analysis operating conditions prone to the risk of carbon deposition are excluded. Also the impact on the balance of plant is taken into account. Results show, that depending on the fuel, system design and parameters the electrical efficiency of the fuel cell alone can vary between 35 and 71%. From this, depending on the system parasitic consumption and losses of up to 8% points have to be subtracted. Thus, net AC efficiencies reach 30 to 63%.
Finally a new system design and operating regime is proposed, which can significantly raise the DC efficiency while reducing the parasitic consumption by adjusting the gas treatment and operating parameters. Modelling results of new design show net AC system efficiencies of up to 72%.
In the presented work a medium-sized integrated system based on a sodium heat pipes powered allothermal fluidized bed gasification and SOFC is introduced, simulated and validated in Aspen Plus. ...Suitable feedstocks for such fluidized bed gasification systems are for example waste and biomass, especially wood. The concept development and evaluation have been conducted as part of the EU FCH-JU project SOFCOM.
During the allothermal heat pipes gasification process heat for the endothermic gasification reactions is transported into the gasification chamber via the heat pipes. The heat pipes allow low temperature differences using mainly latent heat transport. Inside the heat pipes sodium is evaporated on the hot side by a heat source (i.e. combustion chamber) and condensed on the cold side (i.e. gasification chamber). Heat pipes based gasification has proven to be a reliable technology at different installations by the company Agnion energy GmbH and others. The gasifier model has been validated against data from this type of gasifier. The SOFC model applied is a thermodyamic model, which has been developed in the frame of SOFCOM and already described in detail in other works.
In the presented system configuration the product gas from the gasifier is cleaned during several process steps at an intermediate temperature of 350°C. After the cleaning procedure the gas is introduced into the SOFC anode where it is converted into electricity and high temperature heat at a fuel utilization rate of 80%. At the same time preheated air is fed to the cathode of the SOFC. The SOFC exhaust is fed into a fluidized bed post combustion chamber where residual fuel is burned with residual oxygen. Heat is extracted via the heat pipes from the combustion chamber, as well as the SOFC itself. Combustion exhaust gases are used to preheat the cathode air. Residual exhaust heat is used to generate high pressure superheated steam, which in turn is expanded in a steam turbine. At this point, the steam necessary for the fluidization of the gasifier and gasification agent is not produced in a separate steam generator but instead extracted from the steam turbine. Especially by means of utilization of excess heat from the SOFC and its exhaust gases via the heat pipes and full integration of the steam cycle the electrical efficiency of the combined system reaches up to 62%
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