With whole-body magnetic resonance imaging (wb-MRI), almost the whole bone marrow compartment can be examined in patients with monoclonal plasma cell disease. Focal lesions (FLs) detected by spinal ...MRI have been of prognostic significance in symptomatic multiple myeloma (sMM). In this study, we investigated the prognostic significance of FLs in wb-MRI in patients with asymptomatic multiple myeloma (aMM).
Wb-MRI was performed in 149 patients with aMM. The prognostic significance of the presence and absence, as well as the number, of FLs for progression into sMM was analyzed.
FLs were present in 28% of patients. The presence per se of FLs and a number of greater than one FL were the strongest adverse prognostic factors for progression into sMM (P < .001) in multivariate analysis. A diffuse infiltration pattern in MRI, a monoclonal protein of 40 g/L or greater, and a plasma cell infiltration in bone marrow of 20% or greater were other adverse prognostic factors for progression-free survival in univariate analysis.
We recommend use of wb-MRI for risk stratification of patients with asymptomatic multiple myeloma.
Chromosomal abnormalities have been shown to play a major role in disease evolution of multiple myeloma. Specific changes in interphase cells can be detected by fluorescent in situ hybridization, ...which overcomes the problem of the lack of dividing cells required for conventional cytogenetics.
We analyzed the prognostic value of 12 frequent chromosomal abnormalities detected by fluorescent in situ hybridization in a series of patients (n=315) with newly diagnosed, symptomatic multiple myeloma. All patients underwent frontline autologous stem cell transplantation according to the GMMG-HD3- or GMMG-HD4-trial protocols or analogous protocols.
Univariate statistical analyses revealed that the presence of del(13q14), del(17p13), t(4;14), +1q21 and non-hyperdiploidy was associated with adverse progression-free and overall survival rates independently of the International Staging System (ISS) classification. Multivariate analyses showed that only t(4;14) and del(17p13) retained prognostic value for both progression-free and overall survival. According to the presence or absence of t(4;14) and del(17p13) and the patients' International Staging System classification, the cohort could be stratified into three distinct groups: a group with a favorable prognosis absence of t(4;14)/del(17p13) and ISS I, a group with a poor prognosis presence of t(4;14)/del(17p13) and ISS II/III and a group with an intermediate prognosis (all remaining patients). The probabilities of overall survival at 5 years decreased from 72% in the favorable prognostic group to 62% (hazard ratio 2.4; P=0.01) in the intermediate and 41% (hazard ratio 5.6; P<0.001) in the poor prognostic groups.
These results have implications for risk-adapted management for patients with multiple myeloma undergoing high-dose chemotherapy followed by autologous stem cell transplantation and suggest that new treatment concepts are urgently needed for patients who belong to the poor prognosis group. As targeted therapies evolve, different treatment options might have variable success, depending on the underlying genetic nature of the clone.
Over the past decade, treatment options for patients with multiple myeloma (MM) have improved substantially, resulting in better response rates and prolonged overall survival (OS). Nevertheless, MM ...remains a challenging disease, especially if renal insufficiency (RI) or extensive pre-treatment aggravates the assignment of the optimal treatment schedule. In this retrospective study, we analyzed the outcome of lenalidomide plus dexamethasone in 167 patients with relapsed or refractory MM with focus on RI. The baseline creatinine clearance (CLCr) was normal in 94 patients (CLCr ≥ 80 ml/min), while RI was observed in 73 patients, including 40 patients with mild RI (50 ≤ CLCr < 80 ml/min) and 33 patients with moderate or severe RI (CLCr < 50 ml/min). Response rates declined depending on the severity of RI, being 67% among patients with normal kidney function, 60% among patients with mild RI and 49% among patients with moderate or severe RI. Time to progression (TTP) was significantly reduced in patients with severe RI and in case of >2 previous treatment lines. OS was not significantly different between patients with normal and impaired renal function. In contrast, the number of previous treatment lines (2 vs. <2) and the use of novel agents like bortezomib or thalidomide prior to lenalidomide plus dexamethasone therapy had a more adverse effect on OS. In conclusion, lenalidomide plus dexamethasone is an effective regimen for relapsed or refractory patients with MM complicated by RI with manageable toxicity.
Purpose: The aim of our study was to investigate whether dynamic contrast–enhanced magnetic resonance imaging (DCE-MRI) allows visualization
of changes in microcirculation between healthy controls on ...the one side and early/advanced stages of plasma cell disease on
the other.
Experimental Design: We examined a group of 222 individuals consisting of 60 patients with monoclonal gammopathy of undetermined significance
(MGUS), 65 patients with asymptomatic multiple myeloma (aMM), 75 patients with newly diagnosed symptomatic MM (sMM), and 22
healthy controls with DCE-MRI of the lumbar spine.
Results: A continuous increase in microcirculation parameters amplitude A and exchange rate constant kep reflecting vascular volume and permeability, respectively, was detected from normal controls over MGUS and aMM to sMM. For
A and kep , significant differences were found between controls and aMM ( P = 0.03 and P = 0.004, respectively) as well as controls and sMM ( P = 0.001 and P < 0.001, respectively). Although diffuse microcirculation patterns were found in healthy controls as well as MGUS and MM,
a pattern with focal hotspots was exclusively detected in 42.6% of sMM and in 3 MGUS and 3 aMM patients. MGUS and aMM patients
with increased microcirculation patterns showed significantly higher bone marrow plasmocytosis compared with patients with
a low microcirculation pattern.
Conclusions: Our investigations substantiate the concept of an angiogenic switch from early plasma cell disorders to sMM. Pathologic DCE-MRI
findings correlate with adverse prognostic factors and DCE-MRI identifies a distinct group of patients with increased microcirculation
parameters in aMM and MGUS patients.
1 Department of Internal Medicine Division of Hematology/Oncology, Amyloidosis Clinic, University of Heidelberg
2 Division of Biostatistics (C060), German Cancer Research Center, Heidelberg
3 ...Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg
4 Department of Internal Medicine Division of Hematology/Oncology, University of Heidelberg, Germany
Correspondence: Stefan Schönland MD, Medizinische Klinik V, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. E-mail: stefan.schoenland{at}med.uni-heidelberg.de
We evaluated the Serum Free Light Chain (FLC) test in a series of 133 untreated patients with systemic AL amyloidosis. The FLC test detected the monoclonal gammopathy in 87% compared with 92% for immunofixation of serum and urine in combination. However, both tests proved complementary. The FLC test was also a valuable tool in patients with advanced renal failure in spite of uninvolved light chain retention. Higher FLC levels were associated with higher bone marrow plasmocytosis, poorer Karnofsky index and heart involvement, and therefore reflected disease severity.
Key words: serum-free light chain test, AL amyloidosis, Karnofsky index, bone marrow plasmocytosis, heart disease.
The introduction of rituximab into the primary treatment of malignant lymphomas of the B cell lineage has had a major impact on the management of these diseases. In addition, prolonged exposure to ...rituximab as maintenance therapy has been beneficial in patients with follicular lymphoma and mantle cell lymphoma. For the individual patient, the effect of any prolonged antitumor therapy on the quality of life (QoL) is a very important question. However, so far, the question whether rituximab maintenance therapy may impair QoL in patients with non-Hodgkin’s lymphoma remains unanswered. To investigate this subject, we have performed a prospective randomized trial of rituximab maintenance therapy (8 cycles rituximab 375 mg/m
2
every 3 months) versus observation in patients with CD20+B cell non-Hodgkin’s lymphoma in our institution. Between July 2002 and December 2005, 122 patients were included into the trial. QoL was assessed with the standardized questionnaires EORTC-QLQ-C30, EuroQol-5D, and EuroQol-5D (VAS) in 91 patients. After statistical analysis with the exact Wilcoxon rank sum test, we found no significant differences of the QoL between the rituximab treatment group and the observation group. We conclude that rituximab maintenance therapy seems to be safe and does not impair quality of life in this patient population.
Authorities Dealing with REACH Christiane Heiß; Caroline Hoffmann; Christoph Schulte ...
Chimia,
01/2006, Letnik:
60, Številka:
10
Journal Article
Recenzirano
Odprti dostop
REACH establishes a new principle for assessing the risks of chemicals towards humans and the environment: producers and importers of substances bear the main weight of the new substance stewardship. ...They have to register the substances which are produced or imported with the central EU Chemicals Agency. This includes consideration of uses and possible releases of the chemical throughout the product chain. In addition, producers and importers of chemicals have to ensure that management measures are adequate to control the associated risks over the life-cycle of the chemical. By introducing the 'no data - no market' principle REACH intends to build a dynamic system of growing risk knowledge and risk control for chemicals. In turn, authorities will withdraw from compiling detailed risk assessments and risk reduction strategies. Local, reversible risks and point emission sources will no longer be a topic of expert committees at EU level. During the registration procedure authorities might serve as helpers e.g. by establishing help-desks to support the compilation of the registration dossiers. For the evaluation step of REACH authorities will be able to concentrate on substances and uses of high concern which pose a risk to humans and the environment. Where risks are identified as not adequately controlled and therefore needing regulation at Community level, authorities will propose the respective substances as candidates for authorisation. In addition authorities might suggest restrictions for certain uses. For these legal elements the responsibility still lies with the authorities. Chemicals with persistent, bioaccumulative and toxic properties (PBT-substances) are considered as substances of very high concern and therefore should be subject to authorisation. Producers and importers are required to identify potential PBT-substances in the registration dossiers. Since the responsibility for introducing legal measures remains with the authorities, they also need to implement mechanisms to identify potential candidates during the evaluation procedure.
Abstract Purpose To compare sensitivity of whole-body Computed Tomography (wb-CT) and whole-body Magnetic Resonance Imaging (wb-MRI) with Projection Radiography (PR) regarding each method's ability ...to detect osteolyses in patients with monoclonal plasma cell disease. Patients and methods The bone status of 171 patients was evaluated. All patients presented with multiple myeloma (MM) of all stages, monoclonal gammopathy of unknown significance (MGUS) or solitary plasmacytoma. Two groups were formed. Group A consisted of 52 patients (26 females, 26 males) with an average age of 62 years (range, 45–89 years) who received, both, PR and wb-CT as part of their diagnostic work-up. Group B comprised 119 patients (58 females, 61 males) averaging 57 years of age (range, 20–80 years) who received, both, PR and wb-MRI. Two experienced radiologists were blinded regarding the disease status and assessed the number and location of osteolyses in consensus. A distinction was made between axial and extra-axial lesions. Results In group A, wb-CT revealed osteolyses in 12 patients (23%) that were not detected in PR. CT was superior in detecting lesions in patients with osteopenia and osteoporosis. Compared with PR, wb-CT was significantly more sensitive in detecting osteolyses than PR ( p < 0.001). This was particularly true for axial lesions. Additionally, CT revealed clinically relevant incidental findings in 33 patients (63%). In group B, wb-MRI revealed lesions in 19 patients (16%) that were not detected in PR. All lesions detected by PR were also detected by wb-MRI and wb-CT. Wb-MRI and wb-CT are each superior to PR in detecting axial lesions. Conclusion Wb-CT can detect 23% more focal lesions than PR, especially in the axial skeleton. Therefore, this imaging method should be preferred over PR in the diagnostic work-up and staging of patients with monoclonal plasma cell disease.
Summary
Bone marrow plasma cell infiltration is a crucial parameter of disease activity in monoclonal plasma cell disorders. Until now, the only way to quantify such infiltration was bone marrow ...biopsy or aspiration. Diffusion‐weighted imaging (DWI) is a magnetic resonance imaging‐technique that may mirror tissue cellularity by measuring random movements of water molecules. To investigate if DWI is capable of assessing bone marrow cellularity in monoclonal plasma cell disease, we investigated 56 patients with multiple myeloma or monoclonal gammopathy of undetermined significance, and 30 healthy controls using DWI of the pelvis and/or the lumbar spine. In 25 of 30 patients who underwent biopsy, bone marrow trephine and DWI could be compared. Of the patients with symptomatic disease 15 could be evaluated after systemic treatment. There was a positive correlation between the DWI‐parameter apparent diffusion coefficient (ADC) and bone marrow cellularity as well as micro‐vessel density (P < 0·001 respectively). ADC was significantly different between patients and controls (P < 0·01) and before and after systemic therapy (P < 0·001). In conclusion, DWI enabled bone marrow infiltration to be monitored in a non‐invasive, quantitative way, suggesting that after further investigations on larger patient groups this might become an useful tool in the clinical work‐up to assess tumour burden.
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