49 research outputs found
Nove prognosticke faktory se vztahem k urceni velikosti nadorove masy a aktivity onemocneni v diagnostice a lecbe mnohocetneho myelomu.
No full textMultiple myeloma is one of the most common haematologic malignancies. Currently there are numerous studies looking for new prognostic markers in multiple myeloma. The most important of them are the markers related to proliferative activity of neoplastic cells or to size of tumour mass. The subject of this paper are the results obtained from investigation of some such laboratory markers in a group of patients with monoclonal gammopathies diagnosed diagnosed at our department in the last 3 years. It was analyzed blood and bone marrow samples from 51 patient with new diagnosed monoclonal gammopathies, 14 of them were patients with monoclonal gammopathy of undetermined significance and 37 patients had multiple myeloma. 17 patients with multiple myeloma were treated by high-dose chemotherapy regimen. We assessed significance of selected laboratory markers for differential diagnosis of monoclonal gammopathies and for monitoring of activity of multiple myeloma. Among the investigated parameters it was verified the significance of cell cycle analysis of bone marrow plasmatic population and of the determination of the number of circulating myeloma cells in differential diagnosis of monoclonal gammopathies. In our opinion, the determination of soluble CD138, beta_2-microglobulin and neopterin serum levels can be also recommended as helpful markers for a solution of this problem. Except of beta_2-microglobulin serum level we did not find statistically significant correlation with activity of multiple myeloma in any of the investigated parameters.Summary in EnglishAvailable from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi
Free light chains evaluation as a marker of prognosis and disease response in patients with multiple myeloma and monoclonal gammopathy of undetermined signifcance
No full textin English - MUDr. Jakub Radocha: This project was focused on verifying the usefulness of free light chain (FLC) analysis as the new marker for evaluation of the activity of monoclonal gammopathies. For a long time we have been dedicating our efforts for the standardisation of methods for determination of the basic parameters in myeloma patients. FLC evaluation is not a cheap method and thus there was a need to reconfirm the reliability of information provided by manufacturer for its use. Formulated goals of this project represented the most likely beneficial indications for FLC use in clinical practice. Therefore in the first place, we standardized FLC analysis, then we examined benefit of this analysis in patients with MGUS and also for monitoring of the disease activity in MM patients. For serum analysis we used standard FLC assay (The Binding Site, UK). We collaborated with Registry of Monoclonal Gammopathies database of the Czech Republic (today, more than 4.000 patients). We were able to confirm validity of the prognostic model of MGUS stratification originally developed by Mayo Clinic. Moreover several other independent prognostic factors not included in the mentioned model have been identified, which we plan to include in the further analysis and development of more detailed prognostic..
The Current Issue on Monoclonal Gammopathy of Undetermined Significance from the Perspective of Regional Biochemical Laboratory
No full text3. Summary This thesis deals with the issue of MGUS from the perspective of the regional biochemical laboratory. The dissertation thesis is divided into several chapters. The first part includes general knowledge about monoclonal gammopathies, their basic distribution and characteristics of individual types of monoclonal gammopathies. The next chapter is focused on monoclonal gammopathy of uncletermined significance and their epidemiology, etiology and pathogenesis, disease prevalence, diagnostics and diagnostic criteria. The clinical course of MGUS, prognostic factors and monitoring of monoclonal gammopathy activity are also mentioned. The importance of determining free light chains for the stratification of MGUS risk is also presented separately. The next chapter deals with the basic methods of laboratory diagnostics of MGUS and their pitfalls. The chapter also contains a discussion of the SEKK control system and standardization. The next chapter is devoted to new directions in the diagnosis of monoclonal gammopathies, namely determination of light / heavy chain pairs (Hevylite), immunophenotyping examination, genome examination. In the second part of the dissertation are recorded individual observations of individual cases of monoclonal gammopathies. It includes own laboratory monitoring of individual..
Hyperviscosity Syndrome in Patiens with Monoclonal Gammopathy.
No full textThe thesis deals with the assessment of correlations between selected laboratory parameters used in the diagnosis hyperviscosity syndrome and the determination of monoclonal immunoglobulin. By means of specific examples is graphically illustrated the effect of therapeutic plasmapheresis on laboratory parameters and the clinical condition of the patient. The thesis is divided into theoretical and practical parts. In the theoretical part are summarized the findings of the diagnosis, clinical manifestations and therapeutic methods of hyperviscosity syndrome. Further the history of monoclonal gammopathies is stated with splitting in two basic groups. Within the group of malignant monoclonal gammopathies are described in detail two diseases that are closely related to hyperviscosity syndrome. The first is Waldenström's macroglobulinemia and the second is multiple myeloma. In both diseases is shown their prevalence, definition, etiology, pathophysiology, laboratory findings and clinical symptoms. Further are briefly described methods used for determination of monoclonal immunoglobulin. The practical part describes the laboratory tests, which were obtained laboratory data of the reference group of patients. Laboratory data were processed by regression in Microsoft Office Excel 2007. A statistically..
Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma
No full textLenalidomide-dexamethasone improved outcome in newly diagnosed elderly multiple
myeloma patients. We randomly assigned 662 patients who were age ‡65 years or
transplantation-ineligible to receive induction with melphalan-prednisone-lenalidomide
(MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus lowdose
dexamethasone (Rd). The primary end point was progression-free survival (PFS) in
triplet (MPR and CPR) vs doublet (Rd) lenalidomide-containing regimens. After a median
follow-up of 39 months, the medianPFSwas22 months for the triplet combinations and 21
months for the doublet (P 5 .284). The median overall survival (OS) was not reached in
either arms, and the 4-year OS was 67% for the triplet and 58% for the doublet arms (P 5 .709). By considering the 3 treatment arms
separately, no difference in outcome was detected among MPR, CPR, and Rd. The most common grade ‡3 toxicity was neutropenia:
64% in MPR, 29% in CPR, and 25% in Rd patients (P < .0001). Grade ‡3 nonhematologic toxicities were similar among arms and were
mainly infections (6.5% to 11%), constitutional (3.5% to 9.5%), and cardiac (4.5% to 6%), with no difference among the arms. In
conclusion, in the overall population, the alkylator-containing tripletsMPRandCPRwere not superior to the alkylator-free doublet Rd,
which was associated with lower toxicit
Stanovení volných lehkých řetězců jako pomocného markeru v hodnocení prognózy a odpovědi na léčbu u nemocných s mnohočetným myelomem a monoklonální gamapatií nejasného významu
No full textAuthor's personal copy The problems of proteinuria measurement in urine with presence of Bence Jones protein
No full texta b s t r a c t a r t i c l e i n f o Design and methods: The laboratories received a reference urine sample obtained from a patient with multiple myeloma and lambda free light chain proteinuria and were asked to type the paraprotein using immunofixation and to measure total urinary protein using their established method, most commonly turbidimetry, pyrogallol red assay, and biuret assay. Results: There was a very wide inter-laboratory variability in the protein concentration readouts with up to three-fold difference in some cases. High-resolution two-dimensional electrophoresis and linear mass spectrometry showed that a high proportion of the urinary paraprotein was composed of lambda light chain fragments with molecular weight of 12 kDa. Conclusions: Our results highlight the challenges of reliable and reproducible measurement of urinary protein concentration in the presence of Bence Jones protein
Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in the phase III ASPIRE study
No full textBackground: In ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progression-free survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma. Per protocol, patients received KRd for a maximum of 18 cycles followed by Rd to progression, so the benefit/risk profile of KRd to progression was not established. Methods: This post hoc analysis evaluated the efficacy and safety of KRd versus Rd at 18 months from randomization. Cumulative rates of complete response (CR) or better over time and PFS hazard ratio (HR) at 18 months were evaluated for KRd versus Rd. PFS HRs were also assessed according to cytogenetic risk, prior lines of therapy, and prior bortezomib treatment. Cox regression analysis was used to evaluate PFS HRs. Results: The hazard ratio (HR) for PFS at 18 months was 0.58 versus 0.69 for the overall ASPIRE study. Patients with high-risk cytogenetics, ≥ 1 prior lines of therapy, and prior bortezomib exposure benefited from KRd up to 18 months versus Rd. The HRs for PFS at 18 months in the pre-defined subgroups were lower than those in the overall study. The difference in the proportion of KRd and Rd patients achieving at least a complete response (CR) increased dramatically over the first 18 months and then remained relatively constant. The safety profile at 18 months was consistent with previous findings. Conclusions: The improved PFS HR at 18 months and the continued increase in CR rates for KRd through 18 cycles suggest that there may be a benefit of continued carfilzomib treatment. Trial registration: Clinical trials.gov NCT01080391. Registered 2 March 2010. © 2018 The Author(s)
Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial
No full textBackground: Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. Methods: The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m 2 ) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1–4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. Findings: Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3–35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7–33·8] vs 21·3 months [18·0–24·7]; hazard ratio 0·72, 95% CI 0·58–0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group. Interpretation: Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma. Funding: Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.Full Tex
Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma.
No full textBackground Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. Methods We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Results Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. Conclusions In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391 .)
