Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy.

BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

Randomised phase III trial of FEC120 vs EC-docetaxel in patients with high-risk node-positive primary breast cancer: final survival analysis of the ADEBAR study.

BACKGROUND: Taxane-containing adjuvant chemotherapy has been established as standard treatment in node-positive breast cancer. This study compared efficacy and tolerability of epirubicin (E)/cyclophosphamide (C) followed by docetaxel (Doc) with a dose-dense 5-fluorouracil (F)+E+ C regimen. METHODS: The ADEBAR study was a randomised phase III trial for women with primary invasive breast cancer and ⩾4 metastatic axillary lymph nodes (n=1364). Treatment consisted of four 21-day cycles of E plus C, followed by four 21-day cycles of Doc (EC-Doc), or six 28-day cycles of E plus F plus C (FEC120). RESULTS: Disease-free survival (DFS) was similar in the two treatment arms as shown by multivariate Cox regression adjusted for other prognostic factors (EC-Doc vs FEC120, hazard ratio (HR): 1.087; 95% confidence interval (CI): 0.878-1.346, P=0.444). In addition, there was no significant difference in overall survival (OS) between the two groups (HR: 0.974; 95% CI: 0.750-1.264, P=0.841). Haematologic toxicity was more common in FEC120 recipients; non-haematologic toxicities occurred more frequently in the EC-Doc arm. The serious adverse event rate was significantly higher in the FEC120 group (29.7% vs 22.5%). CONCLUSIONS: EC-Doc provides a feasible and effective alternative therapy option to FEC120 with a different safety profile in this high-risk breast cancer cohort.

Comparative efficacy of selegiline versus rasagiline in the treatment of early Parkinson's disease.

OBJECTIVES: The monoamine oxidase B inhibitors selegiline and rasagiline have not been compared in head-to-head clinical trials in patients with early Parkinson's disease.  The aim of this review was to compare the efficacy of these two agents in this setting. MATERIALS AND METHODS: Randomized, placebo-controlled trials with an endpoint of the mean change from baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) total score were included. Analysis included calculation of the standardized mean differences (SMDs) with 95% confidence intervals (CIs) and Forest Plot analyses for comparisons of pooled results. RESULTS: Five studies with selegiline (n = 1029) and four with rasagiline (n = 820) were included. Treatment duration was 2.5-9 months. Both selegiline and rasagiline showed significant SMDs versus placebo (-0.690, 95% CI -0.811, -0.569 and -1.025, 95% CI -1.230, -0.820; respectively), indicating a significant effect of both drugs on UPDRS. The SMD between selegiline and rasagiline was not significantly different (SMD 0.079; 95% CI -0.010, +0.167). CONCLUSIONS: It appears that selegiline and rasagiline have comparable efficacy in improving Parkinsonian symptoms in patients with early stage disease.

Low-dose 5-fluorouracil in combination with salicylic acid as a new lesion-directed option to treat topically actinic keratoses: histological and clinical study results.

BACKGROUND: Actinic keratoses (AKs) arise after chronic sun exposure. Because long-term ultraviolet (UV) damage may induce proliferation of atypical keratinocytes, treatment of AKs is recommended. OBJECTIVES: To compare 5-fluorouracil 0·5%/salicylic acid 10·0% [low-dose 5-FU/SA (Actikerall®)] with diclofenac 3% in hyaluronic acid (diclofenac HA) and vehicle for the treatment of AKs. METHODS: This was a randomized, placebo-controlled, double-blind, parallel-group, multicentre trial. Patients received topical low-dose 5-FU/SA once daily, its vehicle or diclofenac HA twice daily for a maximum of 12 weeks. The final evaluation was at week 20. The primary objectives were to demonstrate the histological clearance rate of one predefined lesion. The secondary objectives were the improvement of treated lesions, tolerability and safety. RESULTS: There were 470 patients with 4-10 AK lesions each (grade I or II) on the face/forehead or bald scalp included in the study. Low-dose 5-FU/SA was superior to diclofenac HA (P < 0·01) and vehicle (P < 0·0001) for histological clearance of one representative lesion 8 weeks post-treatment. In 72·0%, 59·1% and 44·8% of patients in the low-dose 5-FU/SA, diclofenac HA and vehicle groups, respectively, the week-20 biopsy revealed no AKs. Significantly more lesions were cleared with low-dose 5-FU/SA (74·5%) compared with diclofenac HA (54·6%; P < 0·001) or vehicle (35·5%; P< 0·001). Low-dose 5-FU/SA was superior in terms of complete clinical clearance: 55·4%, vs. diclofenac HA (32·0%, P < 0·001) and vehicle (15·1%P < 0·001). Application-site disorders (mainly burning and inflammation) were more frequent with low-dose 5-FU/SA but mainly of mild to moderate intensity. CONCLUSIONS: Topical low-dose 5-FU/SA demonstrated higher histological and clinical clearance rates vs. diclofenac HA or vehicle. Low-dose 5-FU/SA is an effective lesion-directed treatment for AKs.

Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis. A randomized, double-blind phase I/II study.

BACKGROUND: Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. OBJECTIVE: A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. METHODS: In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm(2) and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). RESULTS: The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. CONCLUSION: Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile.

Effect of mitoxantrone on MRI in progressive MS: results of the MIMS trial.

OBJECTIVE: To evaluate the effects of mitoxantrone (Mx) in progressive multiple sclerosis (MS) on MRI. METHODS: A total of 194 patients with worsening relapsing-remitting or secondary progressive MS were treated with Mx 12 mg/m2 (n = 34), Mx 5 mg/m2 (n = 40), or placebo (n = 36) at 3-month intervals IV over a 2-year period. In preselected MRI centers unenhanced and Gd-enhanced MRI scans were performed at month (M) 0, 12, and 24 in a non-randomized subset of 110 patients and non-selected for MRI criteria. The primary MRI outcome measure was the total number of MRI scans with positive Gd enhancement per group. RESULTS: Twelve mg/m2 Mx failed to reach a significant difference from placebo as measured by the primary MRI outcome at month 12 (p = 0.431) and 24 (p = 0.065). Secondary MRI outcome measures: 5 mg/m2 Mx influenced favorably the number of Gd-enhancing lesions only at month 24 (p = 0.004), but not at month 12 (p = 0.095). Twelve mg/m2 Mx reduced the number of T2-weighted lesions at month 24 (p = 0.027) and showed a positive trend at month 12 (p = 0.069), but not 5 mg/m2 Mx. The number of active MR lesions showed a strong trend toward reduction in the 12 mg/m2 Mx group only at month 24 (p = 0.054). All comparisons are vs placebo, and unadjusted for baseline incidence. CONCLUSIONS: In the MIMS trial 12 mg/m2 Mx does not reduce the number of MRI scans with positive Gd enhancement at month 12 and 24 vs placebo. Results of secondary MRI outcome measures are suggestive of a positive impact of 12 and 5 mg/m2 Mx on some of the Gd enhanced and unenhanced MRI measures as expected from other Mx MRI studies in the past.

[Therapy for overactive detrusor using propiverine]. / Therapie der Detrusorhyperaktivität mit Propiverin.

BACKGROUND: Our aim was to evaluate the efficacy and tolerability of propiverine hydrochloride (propiverine) in daily practice and to check the risk-benefit relation using previously collected data on 4,390 patients. PATIENTS AND METHODS: A total of 2,932 patients with symptoms of overactive bladder were treated with propiverine over a period of 12 weeks using a multicentre post marketing surveillance. At three visits (inclusion, after 4 weeks, after 12 weeks), parameters from the micturition diary (incontinence episodes, frequency of micturition, micturition volume) were recorded. RESULTS: The number of incontinence episodes during daytime decreased during therapy from 3.6+/-3.8 to 1.2+/-2.3. The number of episodes at night decreased from 1.5+/-2.1 to 0.4+/-0.8 (both P<0.001). The mean volume per micturition improved during therapy (from 142.7 ml to 213.3 ml; +49.5%; P<0.0001). Some 85% of the investigators judged the efficacy of propiverine to be good or very good, 2.1% as not sufficient. The most frequent adverse event was dry mouth (17.3% of the patients after 12 weeks) mostly with low severity. More than 70% of the patients reported good or very good tolerability. Only 0.6% of the patients reported insufficient tolerability.

Topical aminolaevulinic acid-based photodynamic therapy as a treatment option for psoriasis? Results of a randomized, observer-blinded study.

BACKGROUND: Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has recently been tried in small open studies for several inflammatory dermatoses including psoriasis. OBJECTIVES: The purpose of this randomized, within patient comparison study was to investigate whether topical ALA-based PDT using a range of light doses can induce a satisfactory response in localized psoriasis. PATIENTS AND METHODS: Twenty-nine patients with chronic plaque type psoriasis were enrolled in the study. After keratolytic pretreatment three psoriatic plaques in each patient were randomly allocated to PDT with 1% ALA and a light dose of 5 J cm(-2), 10 J cm(-2) or 20 J cm(-2), respectively. Treatment was performed twice weekly until complete clearance or for a maximum of 12 irradiations. As a measure of clinical response the psoriasis severity index (PSI) of the three target plaques was assessed separately by an observer blinded to the treatment at baseline, before each PDT treatment and 3-4 days after the last irradiation. RESULTS: Eight patients withdrew prematurely from the study. Keratolytic pretreatment alone reduced the baseline PSI in all three dose groups by about 25%. Subsequent PDT with 20 J cm(-2) resulted in a final reduction of PSI by 59%, PDT with the lower doses of 10 J cm(-2) and 5 J cm(-2) decreased the baseline PSI by 46% and 49%, respectively. The difference in clinical efficacy between 20 J cm(-2) and 10 J cm(-2) or 5 J cm(-2) was statistically significant (P = 0.003; P = 0.02), whereas no difference was found between 10 J cm(-2) and 5 J cm(-2) (P = 0.4). All patients reported some degree of PDT-induced stinging or burning during irradiation. CONCLUSIONS: The unsatisfactory clinical response and frequent occurrence of pain during and after irradiation renders topical ALA-based PDT an inadequate treatment option for psoriasis.

Predictors of treatment failure during highly active antiretroviral therapy (racing trial).

PURPOSE: To determine factors associated with virological failure during long-term treatment with the triple combination of saquinavir soft gel capsule, zalcitabine and zidovudine. METHOD: Open-label, prospective, multicentre study undertaken in private practices and the outpatient department of the Auguste-Viktoria-Hospital. A total of 95 patients with plasma HIV RNA > 5000 copies/ml who had received no more than 6 months pre-treatment with NRTIs and no prior PI therapy received saquinavir soft gel, zalcitabine and zidovudine for 52 weeks, before being randomly assigned to either remain on therapy or switch to nelfinavir, lamivudine and zidovudine for further 52 weeks. RESULTS: Combination therapy with saquinavir, zalcitabine and zidovudine was found to be effective and well tolerated, with virological response to therapy maintained for up to 2 years. In patients responding to therapy, switching to a novel triple regimen did not result in a virological or immunological worsening, but it did not confer an additional clinical benefit. Factors predictive of early treatment failure (virological failure within 16 weeks of treatment initiation) included high viral load and presence of RT mutations at baseline (OR: 0.30, 95% CI 0.11 0.83 and OR 0.13, 95% CI 0.03 0.52, respectively), with baseline viral load and the development of genotypic mutations on therapy being predictive of late treatment failure (16 52 weeks; OR: 0.15, 95% 0.05 0.46 and OR: 0.26, 95% CI < 0.001 1.16, respectively). Plasma saquinavir concentration < 50 mg/ml at 4 weeks was also found to be an independent risk factor for both early and late treatment failure (OR: 1.80, 95% CI 1.23 2.64 and OR: 1.16, 95% CI 0.84 1.60, respectively). CONCLUSIONS: While antiretroviral drug resistance appears to be a principal cause of treatment failure, other factors such as inadequate drug plasma concentrations also play a role.

Clinicopathogenetic significance of chromosomal abnormalities in patients with blastic peripheral B-cell lymphoma. Kiel-Wien-Lymphoma Study Group.

So far, reproducible histomorphologic and immunological criteria to distinguish clinicopathologic subtypes of blastic peripheral B-cell non-Hodgkin's lymphoma (BBCL), especially centroblastic (cb) and immunoblastic (ib) lymphomas, for daily diagnostic use are still lacking. Therefore, we correlated the cytogenetic findings in 126 patients with BBCL with histopathologic diagnoses. Subclassification of cb and ib lymphomas relied on the criteria defined in the updated Kiel classification; these subtypes are also listed in the Revised European-American Lymphoma (REAL) classification and in a preliminary report on the newly established World Health Organization classification, to investigate their clinical significance. Moreover, we performed a multivariate analysis to compare the prognostic significance of cytogenetic findings with the International Index. There were significant differences in the frequency of chromosome aberrations between different BBCL subtypes: t(8;14) was predominantly present in Burkitt's lymphomas, t(14;18) in centroblastic lymphomas, deletions in 8q and 14q, changes of 4q and losses of chromosome 10 in immunoblastic lymphomas; t(11;14) was restricted to blastoid mantle cell lymphomas and associated with a poor prognosis. In cb lymphomas, deletions in 1q42-qter, duplications in 1q23-32, trisomy 5, and changes of 15q were identified as independent prognostic factors. In ib lymphomas, changes of 7q and 8q had stronger impact on survival than the International Index. These findings underline that Burkitt's, cb, ib, and blastoid mantle-cell lymphoma are biologically distinct and clinically relevant entities and that cytogenetic findings can be helpful to subtype BBCL.

Prospective randomized multicenter clinical trial on the use of interferon -2a plus acitretin versus interferon -2a plus PUVA in patients with cutaneous T-cell lymphoma stages I and II.

Cutaneous T-cell lymphoma (CTCL) constitutes a malignant proliferative disease involving mostly CD4(+) T cells arising in the skin. Because of the lack of curative treatment options, interferons (IFN) have been introduced into the therapy of CTCL. Although effective even in advanced disease, response rates were about 50% and the duration of response was short. To improve the results of interferon monotherapy, combinations of IFN with oral photochemotherapy (PUVA) or retinoids were investigated in nonrandomized trials showing higher response rates. We have therefore conducted this prospective randomized multicenter trial to compare these two combination therapies, ie, IFN plus PUVA and IFN plus acitretin. IFN -2a was administered at 9 MU three times weekly subcutaneously in both groups, with lower increasing doses during the first week. Photochemotherapy was applied after oral intake of 8-methoxypsoralen (0.6 mg/kg body weight) 5x weekly during the first 4 weeks, 3x weekly from weeks 5 through 23, and 2x weekly from weeks 24 through 48, with escalating doses beginning with 0.25 J/cm2. Twenty-five milligrams of acitretin was administered daily during the first week, and 50 mg was administered from weeks 2 through 48. Of 98 patients randomized in this study, 82 stage I and II patients were evaluable: 40 in the IFN+PUVA group and 42 in the IFN+acitretin group. With 70% complete remissions in the IFN+PUVA group, this treatment was significantly superior to the IFN+acitretin group with only 38.1% complete remissions. Time to response was significantly shorter in the IFN+PUVA group, with 18.6 weeks compared with 21.8 weeks in the IFN+acitretin group. Side effects were mostly mild to moderate and did not differ significantly in both treatment groups. However, there were more adverse events leading to study discontinuation in the IFN+acitretin group. Based on these findings, we conclude that IFN plus oral photochemotherapy is superior to IFN plus acitretin, inducing more complete remissions in patients with CTCL stages I and II.

Dose intensity phase I/II trial with carboplatin, ifosfamide, etoposide and vincristine combined with filgrastim in patients with small-cell lung cancer.

BACKGROUND: The purpose of the study was to evaluate the feasibility of increasing dose intensity by a stepwise reduction of the time intervals between chemotherapy cycles in separate patient cohorts with small-cell lung cancer. Patients received up to 6 courses of combination chemotherapy with carboplatin, etoposide, ifosfamide and vincristine followed by support with filgrastim. Dose intensity, incidence, duration and severity of neutropenic fever and infections, objective response to chemotherapy, and safety of filgrastim were determined. PATIENTS AND METHODS: 29 patients with small-cell lung cancer (limited disease: 2, extensive disease: 27) were treated with a combination of carboplatin 250 mg/m2 i.v. day 1, ifosfamide 2 g/m2 and etoposide 120 mg/m2 i.v. days 1 and 2, etoposide 120 mg/m2 orally day 3, and vincristine 1.4 mg/m2 day 14. Initially, filgrastim (5 micrograms/kg) was administered subcutaneously from day 7 to 16. With shorter treatment intervals, filgrastim was administered on days 4-16 or 4-14. RESULTS: An overall increase in dose intensity by a factor of 1.44 was achieved after reducing the treatment interval from 27 to 17 days. Further reduction to 14 days was not feasible due to persistent thrombocytopenia. Six patients (21%) developed a total of 9 febrile episodes, and 14 patients (48%) had to be withdrawn from the study before the completion of six cycles of chemotherapy. The median duration of infectious episodes was 6 days. Overall, a total of 22 of 27 evaluable patients had an objective response. Longer treatment intervals resulted in a lower probability for objective response (> or = 23 days: 10/14 patients vs. < or = 17 days: 7/7 patients). CONCLUSION: Filgrastim allows for the reduction of treatment intervals in patients with small-cell lung cancer and increased dose intensity with acceptable hematologic and nonhematologic toxicities.

Serum levels of soluble CD23, but not soluble CD25, predict disease progression in early stage B-cell chronic lymphocytic leukemia.

Serum levels of the soluble forms of CD23 (sCD23) and CD25 (sCD25) were prospectively analyzed with respect to their prognostic relevance in early stage B-cell chronic lymphocytic leukemia (B-CLL). SCD23 and sCD25 levels were determined in 105 patients with newly diagnosed B-CLL (Binet stage A). In 93 of the patients, these levels were correlated with other already established indicators for risk of disease progression, including the histologic pattern of bone marrow infiltration, lymphocyte doubling time (LDT), and the serum level of thymidine kinase (TK). High serum levels of both sCD23 and of sCD25 were associated with a diffuse bone marrow infiltration, a LDT < or = 12 months, and elevated (>5 U/L) serum TK, respectively. Moreover, examination of the clinical course of 76 untreated patients showed that high levels of sCD23, but not of sCD25, at initial diagnosis were linked with disease progression. Furthermore, in a stepwise Cox regression model, high levels of sCD23 and a short LDT were shown to be strong predictors of progressive disease within the first year of disease presentation. Therefore, it appears to be justified to incorporate sCD23 levels into the risk profile of early stage B-CLL and to take them into account for stratification in risk-adapted treatment strategies.

Significance of cytogenetic findings for the clinical outcome in patients with T-cell lymphoma of angioimmunoblastic lymphadenopathy type.

PURPOSE: The aim of this study was to evaluate the significance of cytogenetic findings for the clinical outcome of patients with Angioimmunoblastic Lymphadenopathy (AILD)-Type T-cell lymphoma. MATERIALS AND METHODS: In a retrospective analysis, the cytogenetic findings of 50 patients with AILD-type T-cell lymphoma were correlated with the frequency of spontaneous and therapy-induced remissions and with survival using the statistical methods of Kaplan and Meier and the model of Cox for multivariate analysis. Treatment was not uniform because the patients were treated in different hospitals during a period of 8 years and because a standard therapy has not yet been established. RESULTS: The following cytogenetic findings were associated with a significantly lower incidence of therapy-induced remissions and a significantly shorter survival duration: presence of aberrant metaphases in unstimulated cultures (P = .04 for both parameters); clones with an additional X chromosome (P = .0001 and P = .03, respectively); structural aberrations of the short arm of chromosome 1, preferentially involving 1p31-32 (P < .001 and P = .04, respectively); and complex aberrant clones with more than four aberrations (P = .0003 and P = .005, respectively). Multivariate analysis showed that these cytogenetic findings had a significant influence on survival, but therapy modalities did not. Only the presence of complex aberrant clones was an independent prognostic factor. Trisomy 3 had no effect on survival, but patients without trisomy 5 (P = .08) tended to live longer. CONCLUSION: This is the first study that seems to indicate that cytogenetic findings have prognostic significance in AILD-type T-cell lymphoma. These results must be proven in prospective studies of homogeneously treated patients.

[DMSO in patients with active gonarthrosis. A double-blind placebo controlled phase III study]. / DMSO bei Patienten mit aktivierter Gonarthrose. Eine doppelblinde, plazebokontrollierte Phase-III-Studie.

BACKGROUND: For the patient, the most important aspect of gonarthrosis is pain and the associated impairment of movement.-- METHOD: In a randomized, placebo-controlled, double-blind study involving 112 patients (56 in each of the two groups test substance and placebo) the efficacy and tolerability of DMSO gel 25% applied over a period of three weeks were investigated in comparison with placebo. In addition to an assessment by the doctor of pain under loading while going about daily activities, rest pain, pain on palpation and of loss of mobility, the patient also kept a pain diary.-- RESULTS: In comparison with the gel base used as placebo, percutaneous treatment with DMSO proved to have a clinically relevant analgesic effect on the intensity of loading pain during everyday activities (p = 0.019). A positive effect of DMSO was also seen for pain intensity at rest (p = 0.015) and pressure pain (p = 0.029). The pain diary also reflected these observations. No serious adverse events or changes in laboratory values were observed.

Long-term therapy with the new glucocorticosteroid deflazacort in rheumatoid arthritis. Double-blind controlled randomized 12-months study against prednisone.

The long-term anti-inflammatory and immunosuppressive properties and the safety of deflazacort (Calcort, CAS 14484-47-0) were assessed investigating the effect on clinical symptoms and safety parameters in patients with rheumatoid arthritis compared to prednisone as standard therapy in a randomized double-blind controlled clinical trial. Monitoring was performed according to GCP-guidelines closely in order to have a maximum of the patients entered completed at the end of the 12-month therapy with high data quality. 76 patients, meeting the criteria for classical or definite rheumatoid arthritis and requiring corticosteroid therapy, were randomly allocated to a 12-months treatment with either deflazacort (6 mg/tablet) or the corticoid standard prednisone (5 mg/tablet). Steady state dosage between 1/2 and 3 tablets per day was individually adjusted according to the severity of the clinical symptoms. Due to the close monitoring of the trial in the 6 study centres, 25 patients completed 12 months of deflazacort and 28 patients 12 months of prednisone treatment, being controlled 7 times during the trial. Five efficacy parameters were assessed at each visit: Ritchie Index, duration of morning stiffness, grip strength, effective dosage of study medication and global assessment of disease status. Following safety and tolerance parameters were controlled during the trial: vital signs, weight, Cushing's symptoms and adverse events at each visit; 32 laboratory parameters at 6 visits; ECG at 3 visits; and the global tolerance was assessed at the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Interrater and intrarater variabilities in the evaluation of cutaneous lymphoproliferative T-cell infiltrates. EORTC-Cutaneous Lymphoma Project Group.

Histologic and cytologic evaluation of CTCL is one of the most difficult challenges in dermatopathology. It was the purpose of this study to evaluate the reliability and reproducibility of histologic criteria in CTCL and the interrater and intrarater variabilities. An overall of 2375 ratings of sections from 41 patients with CTCL were given by a panel of 22 dermatopathologists and pathologists familiar with lymphoma histology, some of whom were looking repeatedly at the same series of sections. The results clearly indicate that interrater as well as intrarater variabilities are significant and can be decreased by discussion preceding the evaluation as well as by repeated rating indicating a learning effect. Therefore, histologic evaluations of criteria have to be taken with caution, and statistical evaluation of level of agreement expressed by kappa coefficient is always mandatory in this type of study.

Lymphoepithelioid cell lymphoma (Lennert's lymphoma): clinical features derived from analysis of 108 cases.

In a retrospective analysis of 108 patients with lymphoepithelioid cell lymphoma (LeL) (median age 60, range 21-87 years) initial extent of disease was Ann Arbor stage I in 9%, II in 19%, III in 35%, and IV in 37% of the patients with a high incidence of generalized lymphadenopathy (71%) but seldom extralymphatic disease (13%). Unstable spontaneous remissions were observed occasionally. Complete response rates were 75% in the patients treated with radio- and/or chemotherapy but relapse occurred in 65%. Median overall survival was 16 months with a significantly better prognosis for stage I/II than for stage III/IV disease (P = 0.014). LeL thus seems to possess an unfavourable prognosis possibly to be improved by standardized treatment approaches.