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.
Background. Limited data are available about treatment‐related side effects with respect to laser wavelength in endovenous laser treatment (ELT) of the great saphenous vein (GSV).
Objective. To ...compare the results and side effects of a 940 nm diode and a 1,320 nm neodymium:yttium‐aluminum‐garnet (Nd:YAG) laser.
Methods. Three patient cohorts (A, B, and C) received ELT of the GSV using a 940 nm diode laser at 15 W (group A) or 30 W (group B) or using a 1,320 nm laser at 8 W (group C). In all cases, energy was administered continuously with constant pullback of the laser fiber under perivenous tumescent local anesthesia.
Results. The GSVs of group A (n= 113), group B (n= 136), and group C (n = 33) received ELT. An average linear endovenous energy density of 24, 63, and 62 J/cm and an average endovenous fluence equivalent of 12, 30, and 33 J/cm2 were administered to the vein. Occlusion rates were 95% (group A), 100% (group B), and 100% (group C) at day 1 after ELT and 90.3% (group A), 100% (group B), and 97% (group C) at 3 months after ELT. With the 1,320 nm laser ELT (group C), treatment‐related pain (50%) and the need for analgesics (36%) were significantly reduced (p < .005) in comparison with treatment‐related pain (81%) and the need for analgesics (67%) after the 30 W 940 nm laser ELT (group B). Ecchymosis was also significantly reduced (p < .05) in group C (1,320 nm) compared with group B (30 W, 940 nm).
Conclusion. ELT of the GSV using a 1,320 nm Nd:YAG laser causes fewer side effects compared with 940 nm diode laser ELT.
THIS STUDY WAS FUNDED IN PART BY GRANTS FROM DORNIER MED TECH LASER GMBH AND COOLTOUCH CTEV. THOMAS M. PROEBSTLE, MD, MSC, IS A CONSULTANT TO BOTH COMPANIES.
The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation ...processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10) and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i) malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii) be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii) Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14), t(4;14), hyperdiploidy, 1q21-gain and deletion of 13q14. iv) A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v) As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Thalidomide has potent antimyeloma activity, but no prospective, randomized controlled trial has evaluated thalidomide monotherapy in patients with relapsed/refractory multiple myeloma.
We conducted ...an international, randomized, open-label, four-arm, phase III trial to compare three different doses of thalidomide (100, 200, or 400 mg/day) with standard dexamethasone in patients who had received one to three prior therapies. The primary end-point was time to progression.
In the intent-to-treat population (N=499), the median time to progression was 6.1, 7.0, 7.6, and 9.1 months in patients treated with dexamethasone, and thalidomide 100, 200, and 400 mg/day, respectively; the difference between treatment groups was not statistically significant. In the per-protocol population (n=465), the median time to progression was 6.0, 7.0, 8.0, and 9.1 months, respectively. In patients who had received two or three prior therapies, thalidomide significantly prolonged the time to progression at all dose levels compared to the result achieved with dexamethasone. Response rates and median survival were similar in all treatment groups, but the median duration of response was significantly longer in all thalidomide groups than in the dexamethasone group. Adverse events reported in the thalidomide groups, such as fatigue, constipation and neuropathy, confirmed the known safety profile of thalidomide.
Although thalidomide was not superior to dexamethasone in this randomized trial, thalidomide monotherapy may be considered an effective salvage therapy option for patients with relapsed/refractory multiple myeloma, particularly those with a good prognosis and those who have received two or three prior therapies. The recommended starting dose of thalidomide monotherapy is 400 mg/day, which can be rapidly reduced for patients who do not tolerate this treatment. (
NCT00452569).
Objective Endothermal ablation has become a commonly used technology for occlusion of refluxing great saphenous veins (GSVs). However, the risk for primarily untreated accessory saphenous veins ...(ASVs) to develop reflux during follow-up has not yet been defined. Here, the prevalence and risk of ASV reflux is explored. Methods During a prospective multicenter cohort study on radiofrequency segmental thermal ablation of refluxing GSVs, the presence and reflux status of ASVs were monitored in 93 legs in a single center. Control examinations were performed after 1 week and at 12, 24, 36, and 48 months. Life-table and multiple regression analyses were used to describe frequency and risk factors for presence of reflux in untreated ASVs. Results Of 93 legs, 82 (88%) were available for 4-year follow-up. At baseline, 43 legs (46%) had an anterior ASV detectable by duplex ultrasound, with only two legs (2%) presenting with reflux. During 4 years of follow-up, according to life-table analysis, the proportion of legs with a detectable anterior ASV increased to 71% (n = 65); 32% of all legs and 55% of legs with a detectable anterior ASV exhibited refluxing anterior ASVs. Remarkably, in 35% of all legs with an anterior ASV, this reflux presented as a source of axial reflux, suggesting hemodynamic relevance. Posterior ASVs were detected in only 10 legs during 4-year follow-up, exhibiting reflux in only two cases. Conclusions Whereas posterior ASVs were meaningless, refluxing anterior ASVs occurred in a significant proportion of legs after thermal ablation of GSVs. Whether nonrefluxing anterior ASVs should be treated at the time of GSV ablation needs further examination.
Objectives
Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging ...(DCE-MRI) for survival and local complications in patients with multiple myeloma (MM).
Methods
We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude
A
and exchange rate constant
k
ep
. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures.
Results
Correlation analysis revealed significant positive association between beta2-microglobulin as well as immunoparesis with DCE-MRI parameters
A
and
k
ep
. Additionally,
A
was negatively correlated with haemoglobin levels and
k
ep
was positively correlated with LDH levels. Higher baseline
k
ep
values were associated with decreased vertebral height in a second MRI (
P
= 0.007) and
A
values were associated with new vertebral fractures in the lower lumbar spine (
P
= 0.03 for L4). Pre-existing lytic bone lesions or remission after therapy had no impact on the occurrence of vertebral fractures. Multivariate analysis revealed that amplitude
A
is an independent adverse risk factor for overall survival.
Conclusion
DCE-MRI is a non-invasive tool with significance for systemic prognosis and vertebral complications.
Key Points
•
Qualitative parameters from DCE-MRI are correlated with established factors of disease activity
•
Increased marrow microcirculation might be a risk factor for loss of vertebral height and fractures
•
Amplitude A is an independent predictor for shortened overall survival
Summary
This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE‐MRI) as a non‐invasive imaging technique delivering the ...quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE‐MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE‐MRI of the lumbar spine. Regions of interest were drawn manually on T1‐weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut‐off point of 0·89 arbitrary units had a 2‐year progression rate into symptomatic disease of 80%. In conclusion, DCE‐MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS.
BACKGROUNDLimited data are available about treatment-related side effects with respect to laser wavelength in endovenous laser treatment (ELT) of the great saphenous vein (GSV).
OBJECTIVETo compare ...the results and side effects of a 940 nm diode and a 1,320 nm neodymium:yttium-aluminum-garnet (Nd:YAG) laser.
METHODSThree patient cohorts (A, B, and C) received ELT of the GSV using a 940 nm diode laser at 15 W (group A) or 30 W (group B) or using a 1,320 nm laser at 8 W (group C). In all cases, energy was administered continuously with constant pullback of the laser fiber under perivenous tumescent local anesthesia.
RESULTSThe GSVs of group A (n = 113), group B (n = 136), and group C (n = 33) received ELT. An average linear endovenous energy density of 24, 63, and 62 J/cm and an average endovenous fluence equivalent of 12, 30, and 33 J/cm2 were administered to the vein. Occlusion rates were 95% (group A), 100% (group B), and 100% (group C) at day 1 after ELT and 90.3% (group A), 100% (group B), and 97% (group C) at 3 months after ELT. With the 1,320 nm laser ELT (group C), treatment-related pain (50%) and the need for analgesics (36%) were significantly reduced (p < .005) in comparison with treatment-related pain (81%) and the need for analgesics (67%) after the 30 W 940 nm laser ELT (group B). Ecchymosis was also significantly reduced (p < .05) in group C (1,320 nm) compared with group B (30 W, 940 nm).
CONCLUSIONELT of the GSV using a 1,320 nm Nd:YAG laser causes fewer side effects compared with 940 nm diode laser ELT.
To examine if standard magnetic resonance (MR) imaging of the axial skeleton is sufficient for evaluation of patients with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance ...(MGUS) or if whole-body MR is necessary.
A total of 100 untreated patients with MGUS (n = 27) or any stages of MM (n = 73) were examined with whole-body MR imaging and MR imaging of the axial skeleton. The study was approved by the institutional ethics committee, and written informed consent was given. Spinal pattern ("no diffuse involvement" or "diffuse involvement" as assessed from the signal intensity of the spinal bone marrow), serum parameters, and stage of disease were correlated with the probability of detecting extra-axial lesions with and without destruction of cortical bone by using a multiple logistic regression model.
Of 100 patients, 39 had lesions in the axial skeleton and 37 had lesions in the extra-axial skeleton. Of the latter group, nine patients had no axial lesions and 13 patients had lesions that violated cortical bone, which implied an increased fracture risk. Because of the extraaxial location, lesions in these patients could be diagnosed with whole-body MR only. In addition, no single or combination of clinical factors observed (stage of disease, serum parameters, and spinal pattern) allowed investigators to identify patients with a significantly increased probability of having extra-axial lesions or lesions violating cortical bone.
Whole-body MR imaging has potential for use in the initial work-up of patients with MGUS or MM, since almost one-half of all observed lesions would have been missed by using spinal MR imaging only and clinical parameters could not exclude the presence of extra-axial lesions.
Purpose: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with high temporal resolution enables the detection of microcirculation
variables amplitude A and exchange rate constant k ep . ...In this study, the prognostic value of the DCE-MRI variables for overall survival and event-free survival in patients with
progressive multiple myeloma was investigated.
Experimental Design: Between 1999 and 2001, 65 patients with progressive or relapse of multiple myeloma requiring therapy were investigated with
DCE-MRI of the lumbar spine before start of therapy. The contrast uptake was quantified using a two-compartment model with
the output variables amplitude A and exchange rate constant k ep reflecting bone marrow microcirculation. The estimated median follow-up was 56 months. Event-free survival and overall survival
were investigated for DCE-MRI variables and for established prognosis variables (β 2 -microglobulin, lactate dehydrogenase, albumin, and age).
Results: Using a multivariate Cox regression model, β 2 -microglobulin and amplitude A of DCE-MRI were identified as statistically significant prognostic variable of event-free survival with P s of 0.01 and 0.02, respectively. A statistical correlation of DCE-MRI variables with overall survival could not be found.
The multivariate analysis of β 2 -microglobulin, age, lactate dehydrogenase, and albumin revealed β 2 -microglobulin as statistically significant prognostic factor for overall survival in this group of patients ( P < 0.001).
Conclusions: This analysis identifies contrast-enhanced DCE-MRI variable amplitude A reflecting increased bone marrow microcirculation and angiogenesis as a novel and possibly useful prognostic factor in patients
with multiple myeloma. Prospective studies are currently done to further investigate this functional variable for prognosis
and stratification of myeloma patients.
PDF
