Adam Svobodník

Randomized study of interferon beta-1a, low-dose azathioprine,and low-dose corticosteroids in multiple sclerosis

Background Studies evaluating interferon beta (IFNβ) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFNβ does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFNβ with classical immunosuppressive agents, such as azathioprine (AZA) or corticosteroids, commonly used for other autoimmune disorders. Objective The Avonex–Steroids–Azathioprine study was placebo-controlled trial and evaluated efficacy of IFNβ-1a alone and combined with low-dose AZA alone or low-dose AZA and low-dose corticosteroids as initial therapy. Methods A total of 181 patients with relapsing–remitting MS (RRMS) were randomized to receive IFNβ-1a 30 μg intramuscularly (IM) once weekly, IFNβ-1a 30 μg IM once weekly plus AZA 50 mg orally once daily, or IFNβ-1a 30 μg IM once weekly plus AZA 50 mg orally once daily plus prednisone 10 mg orally every other day. The primary end point was annualized relapse rate (ARR) at 2 years. Patients were eligible for enrollment in a 3-year extension. Results At 2 years, adjusted ARR was 1.05 for IFNβ-1a, 0.91 for IFNβ-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFNβ-1a, 20.7% for IFNβ-1a plus AZA, and 17.5% for combination. There were no statistically significant differences among groups for either measure at 2 and 5 years. Percent T2 lesion volume change at 2 years was significantly lower for combination (+14.5%) versus IFNβ-1a alone (+30.3%, P < 0.05). Groups had similar safety profiles. Conclusion In IFNβ-naïve patients with early active RRMS, combination treatment did not show superiority over IFNβ-1a monotherapy.

Autologous versus allogenic bone grafts in instrumented anterior cervical discectomy and fusion: a prospective study with respect to bone union pattern

BackgroundThe purpose of this prospective semi-randomised comparative study was to compare fusion rates, course of fusion, and occurrence of collapse and subsidence of autologous and allogenic bone grafts in instrumented anterior cervical fusion. The number of fused levels and the smoking status were investigated as potential factors influencing the bone-healing process. No similar prospective study on instrumented anterior cervical discectomy and fusion was found in the literature.MethodsSeventy-nine consecutive patients were operated on using the Smith–Robinson technique with a single instrumentation system at one or two levels. Seventy-six cadaverous fibular bone grafts and 37 autologous iliac-crest bone grafts were inserted. All patients were followed up for at least 2 years.ResultsThe radiographs obtained during the follow-up were analysed, and showed no statistical difference in fusion and collapse rate between autografts and allografts. Allografts showed significantly longer time to union. No case of graft migration was observed. No difference was found between fusion and collapse rate with respect to the number of fused levels in general, but greater time to union was seen in two-level fusions. When one- and two-level subgroups were compared, there was no evidence of any significant difference in fusion or collapse rates between autografts and allografts, and the healing process took longer in allogenic grafts. Smoking status did not alter any of the fusion or collapse rates, or the course of bone fusion.ConclusionsThis study demonstrates that allografts are suitable substitutes for autografts in instrumented ACDF. Prolonged time to union observed in allogenic bone grafts does not seem to be an important factor in instrumented procedures. Two-level grafting does not imply a significantly lower fusion rate, but longer time to union can be expected than with single-level instrumented procedures in both allograft and autograft subgroups. Our relatively small number of patients may not have been sufficient to decipher significant differences between smokers and non-smokers in the rate or course of fusion as previously reported.

Quality of Life in 650 Lung Cancer Survivors 6 Months to 4 Years After Diagnosis

OBJECTIVE To present the results of a quality-of-life (QOL) assessment performed with the current version of the Lung Cancer Symptom Scale (LCSS) questionnaire in a large single-institutional data set of 650 patients with lung cancer. PATIENTS AND METHODS The study group included 650 patients with pathologically confirmed primary lung cancer whose conditions were diagnosed and/or treated at the Mayo Clinic in Rochester, Minn, between January 1, 1997, and December 31, 2001. The QOL assessment was performed using the self-administered LCSS questionnaire (version 2) 6 months to 4 years after the diagnosis of lung cancer. RESULTS The item response rate for all 9 LCSS questions was 94.2% with a minimum of 92.9%. Significant differences in overall QOL by sex (P=.04), Karnofsky scale (P<.001), weight loss (P<.001), disease stage (P<.001), and histology (P=.001) were found, but no significant differences in overall QOL by age (P=.17) or marital status (P=.06) were observed. CONCLUSION Our data suggest that QOL in patients with lung cancer at varying times after diagnosis highly correlates with baseline prognostic factors (disease stage, histology, Karnofsky scale, weight loss, and sex).

Prognostic factors for survival after autologous transplantation: a single centre experience in 133 multiple myeloma patients

Summary:Autologous stem cell transplantation (ASCT) has an established role in the treatment of symptomatic multiple myeloma (MM). Our aim was to analyse the impact of selected prognostic parameters on the survival of patients with MM after ASCT. The new International Staging System (ISS) was also evaluated. A total of 133 MM patients were transplanted in our centre between 1995 and 2002. Following ASCT, 35% of patients were in complete remission (CR) and 60% were in partial remission (PR). The median progression-free (PFS) and overall (OS) survival from transplantation were 29.5 and 68.8 months, respectively. Transplant-related mortality (TRM) was 3%. On multivariate analysis, factors associated with significantly shorter OS were lack of CR after transplant (P=0.002, hazard ratio (HR): 3.1), stage 3 according to ISS (P=0.001, HR: 3.0) and age at transplant over 60 years (P=0.035, HR: 2.0). The status of disease before ASCT did not significantly affect PFS and OS after transplantation. We conclude that ASCT is a safe and effective procedure in MM patients, associated with low TRM. The survival after ASCT was dependent on response after ASCT, stage according to ISS and age.

Second autologous transplantation for multiple myeloma patients relapsing after the first autograft -- a pilot study for the evaluation of experimental maintenance therapies. Report of the prospective non-randomized pilot study of the Czech Myeloma Group.

Background: High-dose chemotherapy followed by autologous stem cell transplantation (AT) is accepted as first-line therapy for patients with multiple myeloma (MM), with very good tolerance and low mortality (2–3%). Study Design: We tested repeated transplantation with different experimental maintenance therapies in patients with MM relapsing/progressing after first AT. Results were compared using intra-individual analyses, therefore inter-individual differences are excluded (T2 model). Patients and Methods: Between January 1997 and January 2003, 32 patients with relapsing/progressing MM after first AT were included in the pilot study, median follow-up was 75.2 months. They received the following experimental therapies: IL-2-activated PBSC (10 pts), pamidronate (4 pts), thalidomide (15 pts), consolidation chemotherapy CED (3 pts). Results: Sensitivity to C-VAD reinduction chemotherapy (4 cycles) was 50%, response to the second AT compared to the first was better in 7, the same in 16 and worse in 9 patients. Toxicity of the first and second transplantation was similar and usually did not exceed grade II (SWOG). Transplant-related mortality was 3% (1/32). Event-free survival after second AT (EFS II) is known in 22 patients; 7 have achieved prolongation of EFS II versus EFS I. In the whole group median EFS I was 15.7 months, median EFS II was 12.9 months, median overall survival (OS) was 79.1 months; 20/32 patients were alive at the time of analysis. Conclusions: Repeated AT is a feasible and successful strategy in treatment of relapsing MM; response to second AT and toxicity were acceptable and similar to the first AT in our assessment.

Generation of antigen-loaded dendritic cells in a serum-free medium using different cytokine combinations

Dendritic cells (DCs) are antigen-presenting cells that play a critical role in the induction of cytotoxic T-lymphocytes. An optimal method for the generation of DC for clinical use remains to be established. The aim of our study was to find an optimal cytokine combination for DC generation from peripheral blood stem cells (PBSC) and peripheral blood mononuclear cells (PBMC) in serum-free conditions. Serial immunophenotyping enabled us to observe changes in DC content during the culture as well as the development of maturation and activation markers. As a source for DC culture, we used PBSC from patients with multiple myeloma after stem cell mobilization using cyclophosphamide and G-CSF, or PBMC from healthy donors without mobilization. The cells were cultured in a serum-free medium with different cytokine combinations including GM-CSF, TNF-alpha, Flt-3, CD40L, IFN-gamma, IL-1alpha, IL-6, PGE1, and IL-4. The cell cultures were evaluated by immunophenotyping. For PBMC, interleukin-12 assay was performed. For PBSC, the yield of DC as determined by CD83+ cell count ranged from 0. 6 x 10(5) to 30.1 x 10(4) (mean: 9.4 x 10(4)) of DC generated per 1 x 10(6) of initially plated nucleated cells from apheresis. This yield corresponded to (0.3-19.1) x 10(5) (mean: 4.3 x 10(5)) per 1 x 10(6) of CD34+ cells in the apheresis products. For PBMC, the yield was (0.4-24.8) x 10(4) (mean: 2.4 x 10(4)) of DC generated per 1 x 10(6) of initially plated mononuclear cells from venous blood. The cultured cells expressed the mature immunophenotype. No significant differences in cell yield or immunophenotype were detected when comparing different cytokine combinations.

Effects of Low-power Laser Irradiation on Cell Locomotion in Protozoa {

Abstract Low-power lasers are commonly used in human medicine for treatment of various pathological conditions, but mechanisms of their healing effects are still poorly understood. The results of this study provide information related to these effects at the cellular level. Two different protozoan species, Euglena gracilis and Tetrahymena thermophila, were used to study changes in locomotion behavior in response to low-power lasers. The cells were irradiated at 830 and 650 nm generated by a semiconductor laser (99 J/cm2, 360 mW) and a laser pointer (0.75 J/cm2, 5 mW), respectively, and their locomotion was recorded by a TV camera and analyzed using computer software. Exposure to laser light, regardless of the wavelength, resulted in increased cell velocity in both species (P < 0.001). Exposure to 650 nm produced an equal increase in median cell velocity in both E. gracilis (19.0%) and T. thermophila (18.2%), and some increase persisted in the postirradiation 30 s period. Irradiation by the 830 nm laser resulted in a markedly higher response in Tetrahymena (29.4%) than in Euglena (15.2%), and the two median values remained increased after irradiation was discontinued. Different reactions found in the species studied and some mechanisms underlying the response of cells to radiation are discussed.

Efficacy of Pegylated Interferon Alpha-2a and Ribavirin Treatment in Chronic Hepatitis C Patients Depends on Various Baseline Parameters and Early Viral Kinetics

OBJECTIVE The aim of the study was to compare efficacy and viral kinetics during antiviral treatment in different chronic hepatitis C patients--naïve, relapsers and non-responders to previous pegylated interferon alpha (PEG-IFN) and ribavirin treatment, with different genotypes, baseline viremia, body weight, age and gender--and to find some baseline parameters which can predict Sustained Virological Response (SVR; negative serum HCV RNA 24 weeks after treatment). MATERIAL AND METHODS 216 chronic hepatitis C patients were treated with PEG-IFN alpha-2a 180 mg/wk and ribavirin 1 000 or 1 200 mg/day. There were 140 men and 76 women, mean age 40, range 19-70 years; 142 (66 %) naïve, 37 (17 %) relapsers after previous PEG-IFN and ribavirin treatment, and 37 (17 %) non-responders to this treatment. 172 (79,6%) has genotype 1 infection, 4 (1,9 %) genotype 2, 34 (15,6 %) genotype 3, 1 (0,5 %) genotype 4 or 6 infection, and 4 (1,9 %) were infected by unknown viral genotype. Quantitative detection of HCV RNA was done at baseline (216 pts.), 24 hours (83 pts.), 14 days (85 pts.), 28 days (88 pts.), and 84 days (211 pts.) after the first dose of PEG-IFN. RESULTS 195 patients have completed the treatment period and 179 patients the 24-week follow-up period. The probability of SVR was significantly higher (P < 0,001) in naïve patients (74/114, 64,9 %) and relapsers (22/30, 73,3 %) than in non-responders (9/35, 25,7 %) and in genotype 3 patients (23/28, 82,1%) than genotype 1 patient (77/143, 53,8 %) (P = 0,002). The patients with SVR comparing those without SVR have significantly lower weight (mean 72,8 kg vs. 79,1, P = 0,008(, were younger (mean 36,2, vs. 45,5, P > 0,001), and had lower baseline viremia (mean 1,014 3 106 IU/mL vs. 2,415 3 106 IU/mL, P > 0,001). SVR was more frequent in women than in men (43/63, 62,8 % vs. 62/116, 53,4 %) but difference was not significant (P = 0,059). Undetectable serum HCV RNA at week 12 was more predictive of SVR than early viral response (minimum 2 log decrease of serum HCV RNA during the first 12 weeks of treatment)--98/122 (80,3 %) versus 104/141 (73,1 %) of SVR. CONCLUSIONS 1) The monitoring of viral kinetics during first 12 weeks of antiviral therapy in hepatitis C patients was an important predictive value for SVR. 2) Negative serum HCV RNA at week 12 was more predictive of SVR than early viral response. 3) The probability of SVR was significantly higher in patients with lower baseline viremia, body weight and younger adults. 4) Gender was not significant for the efficacy of treatment.

P-921 The 5-years results of the surgical treatment in patients with non-small cell lung cancer (NSCLC): An analysis of 540 patients

The 5-years results of the surgical treatment in patients with non-small cell lung cancer (NSCLS): An analysis of 540 patients

P-55 Chemotherapy with ifosfamide and concomitant radiotherapy in limited disease (LD) small cell lung cancer (SCLC)

A restrospective study of 115 consecutive pts. with limited SCLC was aimed at therapeutic results and toxicity. From preliminary results authors conclude that the use of IFO/CBDCA/VP16 with concomitant raditherapy is an effective therapy, radiotherapy reducing the treatment time.