Author
Sara Bringhen
Bio: Sara Bringhen is an academic researcher from University of Turin. The author has contributed to research in topics: Multiple myeloma & Lenalidomide. The author has an hindex of 45, co-authored 226 publications receiving 11699 citations.
Topics: Multiple myeloma, Lenalidomide, Thalidomide, Bortezomib, Melphalan
Papers published on a yearly basis
Papers
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VU University Amsterdam1, Heidelberg University2, University of Barcelona3, Harvard University4, Complutense University of Madrid5, Lille University of Science and Technology6, Marche Polytechnic University7, Mayo Clinic8, Emory University9, Sapienza University of Rome10, University of Bologna11, University of Arkansas for Medical Sciences12, National and Kapodistrian University of Athens13, Cedars-Sinai Medical Center14, Erasmus University Rotterdam15, University of Navarra16, Centre Hospitalier Universitaire de Nantes17
TL;DR: The R-ISS is a simple and powerful prognostic staging system, and it is recommended for use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.
Abstract: Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (l...
1,350 citations
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TL;DR: Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma and anticoagulant prophylaxis reduces frequency of thrombosis.
792 citations
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University of Turin1, Mayo Clinic2, National and Kapodistrian University of Athens3, Harvard University4, University of Arkansas for Medical Sciences5, Wayne State University6, University of Bologna7, Cross Cancer Institute8, University of Tübingen9, Royal Prince Alfred Hospital10, Charité11, Catholic Medical Center12, University of Barcelona13, Lund University14, Cornell University15, Norwegian University of Science and Technology16, St James's University Hospital17, Emory University18, The Royal Marsden NHS Foundation Trust19, Cedars-Sinai Medical Center20, Erasmus University Rotterdam21, Cleveland Clinic22
TL;DR: This manuscript summarizes the available evidence and recommends a prophylaxis strategy according to a risk-assessment model for venous thromboembolism (VTE), and recommends low-molecular-weight heparin (LMWH), warfarin or aspirin.
Abstract: The incidence of venous thromboembolism (VTE) is more than 1%omicron annually in the general population and increases further in cancer patients. The risk of VTE is higher in multiple myeloma (MM) patients who receive thalidomide or lenalidomide, especially in combination with dexamethasone or chemotherapy. Various VTE prophylaxis strategies, such as low-molecular-Weight heparin (LMWH), warfarin or aspirin, have been investigated in small, uncontrolled clinical studies. This manuscript summarizes the available evidence and recommends a prophylaxis strategy according to a risk-assessment model. Individual risk factors for thrombosis associated with thalidomide/lenalidomide-based therapy include age, history of VTE, central venous catheter, comorbidities (infections, diabetes, cardiac disease), immobilization, surgery and inherited thrombophilia. Myeloma-related risk factors include diagnosis and hyperviscosity. VTE is very high in patients who receive high-dose dexamethasone, doxorubicin or multiagent chemotherapy in combination with thalidomide or lenalidomide, but not with bortezomib. The panel recommends aspirin for patients with <= 1 risk factor for VTE. LMWH (equivalent to enoxaparin 40 mg per day) is recommended for those with two or more individual/myeloma-related risk factors. LMWH is also recommended for all patients receiving concurrent high-dose dexamethasone or doxorubicin. Full-dose warfarin targeting a therapeutic INR of 2-3 is an alternative to LMWH, although there are limited data in the literature with this strategy. In the absence of clear data from randomized studies as a foundation for recommendations, many of the following proposed strategies are the results of common sense or derive from the extrapolation of data from many studies not specifically designed to answer these questions. Further investigation is needed to define the best VTE prophylaxis.
763 citations
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University of Turin1, University of Salamanca2, Mayo Clinic3, Roswell Park Cancer Institute4, Emory University5, VU University Medical Center6, National and Kapodistrian University of Athens7, Cross Cancer Institute8, University of Ostrava9, Harvard University10, Cedars-Sinai Medical Center11, University of Navarra12, Erasmus University Rotterdam13
TL;DR: The frailty score predicts mortality and the risk of toxicity in elderly myeloma patients and is proposed for the measurement of frailty in designing future clinical trials.
533 citations
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TL;DR: Among patients with newly diagnosed myeloma, survival in recipients of a hematopoietic stem- cell autograft followed by a stem-cell allograft from an HLA-identical sibling is superior to that in recipient of tandem stem- Cell autografteds.
Abstract: Background In this trial of the treatment of newly diagnosed multiple myeloma, we compared a protocol that entailed a hematopoietic stem-cell autograft followed by an allograft from an HLA-identical sibling with a protocol of tandem autografts. Methods We enrolled 162 consecutive patients with newly diagnosed myeloma who were 65 years of age or younger and who had at least one sibling. All patients were initially treated with vincristine, doxorubicin, and dexamethasone, followed by melphalan and autologous stem-cell rescue. Patients with an HLA-identical sibling then received nonmyeloablative total-body irradiation and stem cells from the sibling. Patients without an HLA-identical sibling received two consecutive myeloablative doses of melphalan, each of which was followed by autologous stem-cell rescue. The primary end points were overall survival and event-free survival. Results After a median follow-up of 45 months (range, 21 to 90), the median overall survival and event-free survival were longer in th...
497 citations
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Cedars-Sinai Medical Center1, University of Salamanca2, University of Arkansas for Medical Sciences3, Mayo Clinic4, Alexandra Hospital5, Lund University6, Karolinska Institutet7, Ankara University8, Washington University in St. Louis9, Cross Cancer Institute10, University of Turin11, Royal Prince Alfred Hospital12, University of Texas MD Anderson Cancer Center13, University of Pavia14, Harvard University15, University of Bologna16, The Royal Marsden NHS Foundation Trust17
TL;DR: The European Group for Blood and Bone Marrow Transplant/International Bone Marrows Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system to adequately assess clinical outcomes in myeloma.
Abstract: New uniform response criteria are required to adequately assess clinical outcomes in myeloma. The European Group for Blood and Bone Marrow Transplant/International Bone Marrow Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system. Categories for stringent complete response and very good partial response are added. The serum free light-chain assay is included to allow evaluation of patients with oligo-secretory disease. Inconsistencies in prior criteria are clarified making confirmation of response and disease progression easier to perform. Emphasis is placed upon time to event and duration of response as critical end points. The requirements necessary to use overall survival duration as the ultimate end point are discussed. It is anticipated that the International Response Criteria for multiple myeloma will be widely used in future clinical trials of myeloma.
2,411 citations
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TL;DR: Guidelines summarize and evaluate all available evidence at the time of the writing process, on a particular issue with the aim of assisting health professionals in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome.
Abstract: ACS
: acute coronary syndrome
AMPLIFY
: Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-line Therapy
aPTT
: activated partial thromboplastin time
b.i.d.
: bis in diem (twice daily)
b.p.m.
: beats per minute
BNP
: brain natriuretic peptide
BP
: blood pressure
CI
: confidence interval
CO
: cardiac output
COPD
: chronic obstructive pulmonary disease
CPG
: Committee for Practice Guidelines
CRNM
: clinically relevant non-major
CT
: computed tomographic/tomogram
CTEPH
: chronic thromboembolic pulmonary hypertension
CUS
: compression venous ultrasonography
DSA
: digital subtraction angiography
DVT
: deep vein thrombosis
ELISA
: enzyme-linked immunosorbent assay
ESC
: European Society of Cardiology
H-FABP
: heart-type fatty acid-binding protein
HIT
: heparin-induced thrombocytopenia
HR
: hazard ratio
ICOPER
: International Cooperative Pulmonary Embolism Registry
ICRP
: International Commission on Radiological Protection
INR
: international normalized ratio
iPAH
: idiopathic pulmonary arterial hypertension
IVC
: inferior vena cava
LMWH
: low molecular weight heparin
LV
: left ventricle/left ventricular
MDCT
: multi-detector computed tomographic (angiography)
MRA
: magnetic resonance angiography
NGAL
: neutrophil gelatinase-associated lipocalin
NOAC(s)
: Non-vitamin K-dependent new oral anticoagulant(s)
NT-proBNP
: N-terminal pro-brain natriuretic peptide
o.d.
: omni die (every day)
OR
: odds ratio
PAH
: pulmonary arterial hypertension
PE
: pulmonary embolism
PEA
: pulmonary endarterectomy
PEITHO
: Pulmonary EmbolIsm THrOmbolysis trial
PESI
: pulmonary embolism severity index
PH
: pulmonary hypertension
PIOPED
: Prospective Investigation On Pulmonary Embolism Diagnosis
PVR
: pulmonary vascular resistance
RIETE
: Registro Informatizado de la Enfermedad Thromboembolica venosa
RR
: relative risk
rtPA
: recombinant tissue plasminogen activator
RV
: right ventricle/ventricular
SPECT
: single photon emission computed tomography
sPESI
: simplified pulmonary embolism severity index
TAPSE
: tricuspid annulus plane systolic excursion
Tc
: technetium
TOE
: transoesophageal echocardiography
TTR
: time in therapeutic range
TV
: tricuspid valve
UFH
: unfractionated heparin
V/Q scan
: ventilation–perfusion scintigraphy
VKA
: vitamin K antagonist(s)
VTE
: venous thromboembolism
Guidelines summarize and evaluate all available evidence at the time of the writing process, on a particular issue with the aim of assisting health professionals in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk-benefit-ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help the health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.
A great number of Guidelines have …
2,113 citations
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Spanish National Research Council1, National and Kapodistrian University of Athens2, Rabin Medical Center3, University of Münster4, Charles University in Prague5, Sapienza University of Rome6, University of Turin7, Medical University of Lublin8, Peking University9, Harvard University10, Millennium Pharmaceuticals11, Johnson & Johnson12
TL;DR: Bortezomib plus melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy was superior to melphAlan-predisonsone alone.
Abstract: The time to progression among patients receiving bortezomib plus melphalan– prednisone (bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan–prednisone alone (control group) (hazard ratio for the bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the bortezomib group (P = 0.008). Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan–prednisone. Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group (53% vs. 44%, P = 0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%). Conclusions Bortezomib plus melphalan–prednisone was superior to melphalan–prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)
1,728 citations
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Mayo Clinic1, University of Navarra2, Harvard University3, Cedars-Sinai Medical Center4, Memorial Sloan Kettering Cancer Center5, Emory University6, National and Kapodistrian University of Athens7, University of Turin8, Mount Sinai Hospital9, University of Texas MD Anderson Cancer Center10, Heidelberg University11, Alfred Hospital12, University Health System13, Carolinas Healthcare System14, University of Bologna15, Aalborg University16, Dalhousie University17, Erasmus University Rotterdam18, Roswell Park Cancer Institute19, Columbia University20, University of Toulouse21
TL;DR: Several aspects of disease response assessment are clarified, along with endpoints for clinical trials, and future directions for disease response assessments are highlighted, to allow uniform reporting within and outside clinical trials.
Abstract: Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments.
1,681 citations
01 Aug 2016
TL;DR: Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies.
Abstract: 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies. 4.2 Posology and method of administration Oral administration. Posology The dose is one tablet of 35mg of trimetazidine twice daily during meals. Special populations Renal impairment In patients with moderate renal impairment (creatinine clearance [30-60] ml/min) (see sections 4.4 and 5.2), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Elderly Elderly patients may have increased trimetazidine exposure due to age-related decrease in renal function (see section 5.2). In patients with moderate renal impairment (creatinine clearance [30-60] ml/min), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Dose titration in elderly patients should be exercised with caution (see section 4.4). Health Products Regulatory Authority
1,677 citations