Fifteen years of single center experience with stem cell transplantation for multiple myeloma: a retrospective analysis.

INTRODUCTION: Autologous stem cell transplantation (ASCT) became standard of care for patients with multiple myeloma (MM) under the age of 65 years. We routinely perform ASCT for newly diagnosed MM since 1996 in our department. PATIENTS AND METHODS: We retrospectively analyzed all 285 transplants in 185 patients done for MM from January 1996 till December 2010. We analyzed overall survival (OS) and progression-free survival (PFS) regarding conditioning, stage, complete or very good partial remission (CR, VGPR) achievement, renal impairment, single vs. double transplant. RESULTS: Estimated 10-years survival of the whole set of patients is 39% (median survival 95 months). Patients with renal impairment show same OS as those without (p = 0.22). Patients show similar overall survival and event free survival regardless of type of transplant. We observed better outcome in terms of overall survival in patients treated with new drugs (p = 0.0014). Reaching CR or VGPR was not translated into better OS (p = 0.30) and EFS (p = 0.10). Also stage of the disease and whether single or double transplant was used did not make any significant difference in the outcome. CONCLUSION: Stem cell transplantation greatly improved outcome of patients with MM. Poor outcome of allogeneic transplantation in our group of patients is related to high transplant related mortality (20% vs. 0%) and unexpected high relapse rate. There is a trend towards better survival, when new drugs are incorporated at any time in the course of the disease. This fact supports hypothesis that use of these drugs with ASCT should translate into better long-term outcome.

Elevated serum soluble endoglin (sCD105) decreased during extracorporeal elimination therapy for familial hypercholesterolemia.

Extracorporeal elimination is a method of LDL-lowering therapy that is used in severe familial hypercholesterolemia (FH) after other therapeutic approaches have failed. There are currently no universally accepted biomarkers that would allow determining necessary intensity of therapy and frequency of future therapeutic interventions. An ideal tool for immediate evaluation would be a readily measurable serum marker. We hypothesized that soluble endoglin (sCD105), a recently described indicator of endothelial dysfunction, may represent such a tool. Eleven patients with FH (three homozygous, eight heterozygous; Fredrickson type IIa, IIb) that have been monitored for 4.5+/-2.8 years were treated; eight by LDL-apheresis and three by hemorheopheresis. 40 sCD105 measurements were done, before and after two consecutive elimination procedures. Baseline serum sCD105 levels were significantly higher in the patients (5.74+/-1.47 microg/l in series I, 6.85+/-1.85 microg/l in series II) than in the control group (3.85+/-1.25 microg/l). They decreased to normal after LDL-elimination (p=0.0003) in all except for one patient. This return to normal was not due to a non-specific capture of endoglin in adsorption or filtration columns as demonstrated by measurement of sCD105 before and after passage through the elimination media. We conclude that the soluble endoglin levels in patients with severe FH remain elevated despite long-term intensive therapy and that they decrease after extracorporeal elimination. Endoglin can therefore serve as a marker for evaluation of the treatment efficacy and of the decreased atherosclerotic activity in patients with FH treated by extracorporeal LDL-cholesterol elimination.

Solitary extramedullary plasmacytoma in the oropharynx: advantages of intensity-modulated radiation therapy.

We report a case of a 59-year-old man with solitary extramedullary plasmacytoma in his oropharynx. Because the diagnosis is rare and there is only limited experience in the literature based on retrospective data, the optimal planning target volume and optimal dose of radiation therapy (RT) are still controversial. The frequently discussed problem is the necessity of first echelon lymph node irradiation because it is associated with a higher rate of complications such as xerostomia caused by damage to salivary glands. In order to prevent late toxicity, intensity-modulated RT with the use of simultaneous integrated boost and parotid salivary gland sparing was used in this patient's treatment. The RT was performed in 23 identical fractions, the primary tumor region was irradiated with a dose of 46 Gy and the first echelon lymph node region with the risk of subclinical disease with a dose of 41.4 Gy; the dose per fraction was 2 Gy and 1.8 Gy, respectively. The patient is alive and well > 20 months after the irradiation, without any evidence of disease. Parotid gland function remained intact, and no xerostomia occurred. This is the first report of the use of intensity-modulated RT with parotid gland sparing in the treatment of solitary extramedullary plasmacytoma in the head and neck region.

Optimization of therapeutic procedure during LDL-apheresis - verification of the computerized model in clinical practice.

UNLABELLED: LDL-apheresis is a very effective method in the treatment of resistant hypercholesterolemia when other therapies fail. To maximize the efficacy of the use of LDL-absorbers, we created a computerized model. The aim of this study is to verify it in clinical use. PATIENTS AND METHODS: A therapeutic technique of immunoadsorption was used, applying a pair of Lipopak columns (Pocard, Russia). Plasma was separated by a continuous-flow plasma separator (Cobe Spectra, USA); adsorption was controlled by adsorption-desorption equipment Adasorb (Medicap, Germany). 494 LDL-apheresis procedures had been performed in nine patients with primary hypercholesterolemia in the earlier, initial study; 47 other procedures (202 therapeutic cycles) were used in this verification study. The program for procedure planning uses Microsoft Excel for Windows. Complex metabolism of the LDL-cholesterol was neglected (owing to the short-time period of the procedure) and the procedure calculated as continuous filtration. The input enterer into the program includes basic patient data (mass, height, sex and initial plasma LDL level in mmol/L). RESULTS: The results show a very good match between calculated levels and the real laboratory results in most procedures, but in some procedures we observed minor differences (0.05 mmol/L), which was caused by procedure adjustments due to technical reasons. However, some methodological and medical details must be carefully observed (initial cholesterol level, correct calculation of plasma volume, and the precise capacity of adsorbers that must not be overshot); as they influence the correct match between calculated and real results significantly. CONCLUSIONS: Although our software uses a fairly simplified model of the LDL-cholesterol kinetics during the LDL-apheresis, it is providing a great aid in the procedure planning. It is also suitable for practical use because it only requires a few commonly used and readily available input values.

Safety and tolerability of long lasting LDL-apheresis in familial hyperlipoproteinemia.

The aim of this work is to arbitrate the incidence of side effects and tolerability of long lasting LDL-apheresis in familial hyperlipoproteinemia. 1200 procedures were performed and the last 463 of them were evaluated. An immunoadsorption method of LDL-apheresis was used (continuous blood cell separator Cobe Spectra; secondary device: automated adsorption-desorption ADA, Medicap; absorption columns: Lipopak). As a whole, 6.26% adverse events were found and subsequently resolved by standard symptomatic therapy. Vaso-vagal reactions (symptoms of neurovegetative lability) were the most common adverse effects, presented as malaise, weakness, slight and short-term drop in blood pressure or other general signs. They were all well controlled by symptomatic therapy. We conclude that LDL-apheresis in the hands of experienced personnel is a safe procedure. An acceptable procedure duration limit, balancing the possibility to achieve a targeted cholesterol level while still maintaining an acceptable patient tolerance, was confirmed to be 4 hours.

Optimization of the therapeutic procedure during LDL-apheresis--a computerized model.

UNLABELLED: LDL-apheresis is a very effective method for the treatment of resistant hypercholesterolemia when other therapy (dietary, or medication) fails. To maximize the efficacy of the LDL-absorbers we aimed to create a computerized model. PATIENTS AND METHODS: The therapeutic technique of immunoadsorption was used, applying a pair of columns, the Lipopak, Pocard, Russia. Plasma was separated by a continuous-flow plasma separator, the Cobe Spectra, USA; adsorption was controlled by adsorption-desorption equipment, ADA, Medicap, Germany. 494 LDL-apheresis procedures (treatment interval 17.5+/-1.6 days) were used to treat nine patients with primary hypercholesterolemia followed during the consecutive 3.6+/-0.5 years. Metabolism of LDL-cholesterol is known to be multicompartmental and dynamic, but for the short-time period of the procedure it can be simplified and one can calculate the procedure as a continuous filtration. We developed a program for procedure planning, using Microsoft Excel for Windows. Inputs inserted into the program include only basic patient data (mass, height, sex and initial plasma LDL level in mmol/l). RESULTS: The results show a very promising match between our planning of the procedures and the real laboratory results. The drop in calculated vs real plasma LDL-cholesterol level differ no more than +/-10%. CONCLUSIONS: Although our software does not take into account many well known details about the metabolism of cholesterol, in given conditions it can provide a fairly precise prediction of procedure parameters. It is also suitable for practical use, because it requires only a few commonly used and readily available input values. Immunoadsorption with Pocard absorbers is a potent and safe method of therapy in indicated patients.