Association Study of Selected Genetic Polymorphisms and Occurrence of Venous Thromboembolism in Patients With Multiple Myeloma Who Were Treated With Thalidomide

Almáši, Martina; Ševčı́ková, Sabina; Slabý, Ondřej; Kaisarová, Petra; Maisnar, Vladimír; Penka, Miroslav; Pika, Tomáš; Pour, Luděk; Radocha, Jakub; Scudla, Vlastimil; Šváchová, Hana

doi:10.1016/j.clml.2011.03.024

Cited by 12 publications

(16 citation statements)

References 23 publications

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“…The number of the events in our population is limited, and further analysis is needed to confirm these results, preferably in an independent cohort. Since the SNPs that we report have also been evaluated in patients treated with thalidomide , they may be specific at least for IMiDs, including pomalidomide; however, this has to be confirmed in the future. It is also important that the genetic analysis of the patients who developed VTEs showed that none of these patients carried common polymorphisms of inherited thrompophilia such as FVLeiden and FIIG20210A.…”

Section: Discussionmentioning

confidence: 93%

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Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide‐based regimens

et al. 2013

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Lenalidomide has significant antimyeloma activity but it is associated with a significant risk of venous thromboembolism (VTE). In this study, we assessed clinical and genetic risk factors that may predispose for VTE in myeloma patients who were treated with lenalidomide-based regimens. We analyzed common clinical and selected genetic factors in 200 consecutive, unselected myeloma patients who were treated with lenalidomide-based regimens in a single institution. Twelve patients (6%) developed a VTE (nine deep venous thrombosis and three pulmonary embolism). All VTEs occurred in patients who were receiving aspirin prophylaxis; no patient who received LMWH or acenocoumarol had a VTE. The frequency of VTEs was 9.4% in previously untreated and 4.5% in previously treated patients. VTEs were more frequent in patients >65 years (8.1% vs.

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Section: Discussionmentioning

confidence: 93%

“…The risk of VTE in this context of IMiD therapy may also be related to genetic factors. Data indicate a connection between the development of VTE in MM patients after thalidomide treatment but there is no relevant study for MM patients who are treated with lenalidomide.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide‐based regimens

et al. 2013

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“…5,16 In addition, emerging evidence suggests that the VTE risk associated with the novel immunomodulatory agents may also be exacerbated by specific genomic predispositions, 25 with several studies demonstrating correlations between the incidence of thalidomide or lenalidomide-associated VTE and specific single nucleotide polymorphisms (SNPs) present in genes regulating inflammatory responses and DNA repair. [26][27][28] It has yet to be conclusively determined whether a heightened risk of VTE also occurs in association with monoclonal gammopathy of undetermined significance (MGUS), a related benign condition. While a number of clinical studies suggest that affected individuals have a higher VTE risk than the general population 3,4,29-31 and while recent data suggest that patients with MGUS have laboratory features (such as fibrinogen concentration, FVIII activity, and thromboelastography parameters), which appear to be intermediate between patients with myeloma and the general population, 32 the true magnitude of the heightened VTE risk in MGUS, if any, and the mechanisms underlying this risk have yet to be definitively characterized.…”

Section: Introductionmentioning

confidence: 99%

Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance

Crowley

Kevane

O’Shea

et al. 2016

Clin Appl Thromb Hemost

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The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P< .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies.

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“…While DNA is more stable, integrity and quality of DNA directly influences whole genome amplification [20] and may influence even detection of sin gle nucleotide polymorphisms [21,22]. Repeated freezethaw samples are not recommended even for DNA.…”

Section: Separation Of Cellsmentioning

confidence: 99%

Biobanking – the First Step to Successful Liquid Biopsy Experiments

Almáši¹,

Ševčı́ková²,

Penka³

et al. 2017

Klin Onkol

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A general problem in solving many research questions is the availability of a critical amount of specimens for statistical analysis. Obtaining critical amount of specimens of biological material can be quickly archived by cooperation of biobanks sharing both methodological standards and informations about the availability of samples for research projects.Key words: archiving - biological material - informed consent - multiple myeloma - plasma cells.

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Association Study of Selected Genetic Polymorphisms and Occurrence of Venous Thromboembolism in Patients With Multiple Myeloma Who Were Treated With Thalidomide

Cited by 12 publications

References 23 publications

Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide‐based regimens

Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide‐based regimens

Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance

Biobanking – the First Step to Successful Liquid Biopsy Experiments

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