© F e r r a t a S t o r t i F o u n d a t i o nclassification. 22 In this study, a new serum miRNAs expression profile, potent enough to distinguish newly diagnosed MM and MGUS patients from healthy controls, was created based on TaqMan Low Density Arrays (TLDA). This profile was validated by quantitative realtime PCR (qPCR) on a larger cohort of newly diagnosed and relapsed MM as well as MGUS patients. Moreover, miRNAs levels were correlated with clinical, biochemical and cytogenetic characteristics and survival data. Methods Patients and healthy donorsPeripheral blood (PB) serum samples from 103 newly diagnosed MM patients, 18 MM patients in relapse, 57 MGUS and 30 healthy donors (HD) from the Faculty Hospital Brno, Czech Republic, were obtained for this study. PB serum samples were collected as follows: centrifugation 3500 rpm/15 min/20°C. Samples were frozen as 0.5 mL aliquots, stored at -80°C and thawed only once. For 70 MM and 36 MGUS samples, BMPCs were obtained for routine interphase fluorescence in situ hybridization analysis (I-FISH), as described previously. 23 Patients' and donors' characteristics are described in Table 1 and in the Online Supplementary Table S1. For 6 newly diagnosed MM patients, BMPCs and exosomal and non-exosomal fraction from PB serum were collected. All patients signed an informed consent form approved by the hospital ethical committee before enrollment into this study. MiRNA extractionTotal RNA enriched for miRNAs was extracted from all serum samples using miRNeasy Kit (Qiagen) modified for circulating miRNAs according to the manufacturer's instructions. MiRNA/RNA quantity was assessed on a NanoDrop ND-1000 Spectrophotometer (Thermo Scientific) as measurement of each sample 2 times with mean SD=0.292 ng/μL. All samples fit into the Nanodrop ND-1000 validated measuring range. Exosomes precipitationExosomes were collected using ExoQuick Exosome Precipitation Solution (System Biosciences). Serum samples were centrifuged for 3500 rpm/10 min/4°C, 250 μL of serum was combined with 63 μL of ExoQuick, incubated for 30 min/4°C and centrifuged for 2 min/13000 rpm. Exosomal and non-exosomal fraction was used for miRNA/RNA extraction, as described above. TaqMan Low Density ArraysMegaplex profiling using human TaqMan Low Density miRNA Arrays A+B, v3.0 (TLDA) (Life Technologies) was performed to evaluate the expression of 667 miRNA (see Online Supplementary Methods). QPCR was performed on the ABI7900HT system; raw data were analyzed using SDS software v.2.3, RQ Manager v1.2.1 (Life Technologies). Candidate miRNA confirmation by qPCR and quantification of miRNAIndividual TaqMan miRNA assays for 6 miRNA (hsa-miR-222-002276, hsa-miR-744-002324, hsa-miR-130a-000454, hsa-miR34a-000426, hsa-let-7e-002406, hsa-let-7d-002283, Life Technologies) were used for qPCR on a 7500 Real-Time PCR System. QPCR and reverse transcription was performed following the manufacturer´s recommendations (see Online Supplementary Methods). Absolute quantification to determine the copy number of each miRNA per 1...

BDD induced a high rate of myeloma and renal responses, and treatment was well tolerated.

BackgroundThalidomide maintenance therapy after stem cell transplantation resulted in increased progression-free survival and overall survival in a few trials, but its role in non-transplant eligible patients with multiple myeloma remains unclear. This study assessed the impact of thalidomide-interferon in comparison to interferon maintenance therapy in elderly patients with multiple myeloma. Design and MethodsOf 289 elderly patients with multiple myeloma who were randomized to thalidomide-dexamethasone or melphalan-prednisolone induction therapy, 137 finally completed 9 cycles of induction therapy with stable disease or better and thereby qualified for maintenance treatment. Of these, 128 have been randomized to either thalidomide-interferon or interferon alone. Primary study endpoints were progression-free survival and response rates; secondary endpoints were overall survival, toxicity and quality of life. ResultsThalidomide-interferon maintenance therapy led to a significantly longer progression-free survival compared to interferon (27.7 vs. 13.2 months, P=0.0068), but overall survival was similar in both groups (52.6 vs. 51.4 months, P=0.81) and did not differ between patients aged 75 years or older, or younger patients (P=0.39). Survival after disease progression tended to be shorter in patients on thalidomide-interferon maintenance therapy (P=0.056). Progression-free survival and overall survival tended to be shorter in patients with adverse cytogenetic (FISH) findings compared to the standard risk group but differences were not significant (P=0.084 and P=0.082, respectively). Patients on thalidomide-interferon presented with more neuropathy (P=0.0015), constipation (P=0.0004), skin toxicity (P=0.0041) and elevated creatinine (P=0.026). ConclusionsThalidomide plus interferon maintenance therapy increased progression-free survival but not overall survival and was associated with slightly more toxicity than maintenance with interferon alone. (ClinicalTrials.gov Identifier: NCT00205751).Key words: thalidomide, thalidomide-interferon, progression-free survival, overall survival. Haematologica 2010;95(9):1548-1554. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Ludwig H, Adam Z, Tóthová E, Hajek R, Labar B, Egyed M, Spicka I, Gisslinger H, Drach J, Kuhn I, Hinke A, and Zojer N.Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma.Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma

Aim. Polymyalgia rheumatica (PMR) is a disease presenting with pain and stiffness, mainly in shoulders, hip joints and neck. Laboratory markers of inflammation may bolster diagnosis. PMR afflicts patients over 50 years old, predominantly women, and may also accompany giant cell arteritis. Patients and Methods. 67 patients, who fullfiled Healey´s criteria for PMR in the period between 2004 and 2013 and had positive FDG PET (PET/CT) findings were retrospectively evaluated. FDG uptake was assessed in large arteries, proximal joints (shoulders, hips and sternoclavicular joints), in extraarticular synovial structures (interspinous, ischiogluteal and praepubic bursae). Results. Articular/periarticular involvement (A) was detected in 59/67 (88.1%) patients and extrarticular synovial involvement (E) in 51/67 (76.1%) patients either individually or in combinations. Vascular involvement (V) was detected in 27/67 (40.3%) patients only in combination with articular (A) and/or extraarticular synovial (E) involvement. These combinations were: A+E involvement in 30/67 (44.8%) patients, A+V involvement in 8/67 (11.9%) patients, E+V involvement in 6/67 (9%) patients and A+E+V in 13/67 (19.4%) patients. Conclusions. PMR presents by articular/periarticular synovitis, extraarticular synovitis and can be accompanied by giant cell arteritis. All types of involvement have their distinct FDG PET (PET/CT) finding, which can be seen either individually or in any of their 4 combinations. FDG PET (PET/CT) examination seems to be an advantageous one-step examination for detecting different variants of PMR, for assessing extent and severity and also for excluding occult malignancy.

These data show that plasma cells harbor more aberrations during their transformation into extramedullary form.

Our study suggests a possible prognostic impact of UCA1 expression levels on MM patients.

No abstract

Our aim was to establish whether the pretreatment levels of angiogenesis activators and inhibitors can be used to predict clinical responses to treatment that included high-dose chemotherapy with peripheral stem cell support.We analyzed samples and treatment outcomes of 96 patients with MM enrolled in the CMG 2002 randomized clinical trial and treated with induction chemotherapy and high-dose chemotherapy with stem cell support. Concentrations of vascular endothelial growth factor (VEGF), hepatocytar growth factor (HGF), basic fibroblastic growth factor (bFGF), thrombospondin-1 (TSP-1), endostatin, and angiostatin were measured in the peripheral blood plasma and in the bone marrow plasma at diagnosis.Pretreatment HGF concentrations in the peripheral blood plasma as well as in the bone marrow plasma of patients who achieved complete or very good partial response were significantly lower than those in patients who had partial or worse response. Patients with complete or very good partial response had higher TSP-1 levels in the bone marrow plasma than the partial or insufficient response subgroups. There were no correlations between the pretreatment levels of VEGF, bFGF, endostatin, or angiostatin and the treatment response.Pretreatment concentrations of HGF and TSP-1 were predictive factors for treatment response. Patients with low angiogenesis rate as determined by the relative HGF and TSP-1 concentrations were more likely to achieve complete or very good partial response after high-dose chemotherapy.