Modification of thrombomodulin plasma levels in refractory myeloma patients during treatment with thalidomide and dexamethasone

Corso, Alessandro; Lorenzi, Angela; Terulla, V.; Airò, F.; Varettoni, Marzia; Mangiacavalli, Silvia; Zappasodi, Patrizia; Rusconi, Chiara; Lazzarino, Mario

doi:10.1007/s00277-004-0891-6

Cited by 67 publications

(52 citation statements)

References 14 publications

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“…Acquired activated protein C resistance and a reduction in thrombomodulin level have been associated with an increased risk of DVT. 62,63 No specific coagulation test can predict the high risk of DVT. Endothelial injury produced by the combination of thalidomide with chemotherapy and subsequent restoration of endothelial cell PAR-1 expression are probably factors that promote thrombosis.…”

Section: Thromboembolismmentioning

confidence: 99%

Thalidomide for treatment of multiple myeloma: 10 years later

Palumbo

Façon

Sonneveld

et al. 2008

Blood

287

189

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Thalidomide, bortezomib, and lenalidomide have recently changed the treatment paradigm of myeloma. In young, newly diagnosed patients, the combination of thalidomide and dexamethasone has been widely used as induction treatment before autologous stem cell transplantation (ASCT). In 2 randomized studies, consolidation or maintenance with low-dose thalidomide has extended both progression-free and overall survival in patients who underwent ASCT at diagnosis. In elderly, newly diagnosed patients, 3 independent randomized studies have reported that the oral combination of melphalan and prednisone plus thalidomide (MPT) is better than the standard melphalan and prednisone (MP). These studies have shown better progression-free survival, and 2 have shown improved overall survival for patients assigned to MPT. In refractory-relapsed disease, combinations including thalidomide with dexamethasone, melphalan, doxorubicin, or cyclophosphamide have been extensively investigated. The risks of side effects are greater when thalidomide is used in combination with other drugs. Thromboembolism and peripheral neuropathy are the major concern. The introduction of anticoagulant prophylaxis has reduced the rate of thromboembolism to less than 10%. Immediate thalidomide dose reduction or discontinuation when paresthesia is complicated by pain or motor deficit has decreased the severity of neuropathy. Future studies will define the most effective or the best sequence of combinations which could improve life expectancy. (Blood. 2008;111:3968-3977)

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Section: Thromboembolismmentioning

confidence: 99%

Thalidomide for treatment of multiple myeloma: 10 years later

Palumbo

Façon

Sonneveld

et al. 2008

Blood

287

189

View full text Add to dashboard Cite

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“…Of the 174 primary studies, 15 focused on single adverse events associated with thalidomide, including venous thromboembolism [12][13][14][15][16][17][18][19], neuropathy [20][21][22], severe neutropenia [23], dermatologic side effects [24], hypothyroidism [25], and lymphopenia and infections [26], so these were not included in development of safety profiles. Ninety-five studies were rejected for inadequate safety reporting (72 for incomplete reporting of AEs, 17 for reporting AEs only above a threshold, and 6 for failing to quantify AEs).…”

Section: Study and Patient Characteristicsmentioning

confidence: 99%

Systematic review to establish the safety profiles for direct and indirect inhibitors of p38 Mitogen-activated protein kinases for treatment of cancer

et al. 2008

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“…The majority of thrombotic events described in patients receiving treatment with thalidomide have been venous, but occasional arterial thrombotic events have also been reported. 10 Thalidomide has a wide spectrum of biological effects, including some that have been hypothesized to promote thrombosis such as transient reduction of soluble thrombomodulin levels during the first month of therapy 11 and restoration of endothelial cell PAR-1 expression after damage from cytotoxic agents such as doxorubicin. 12 The latter finding may in part explain the markedly higher TEE risk apparent during thalidomide-anthracycline combination therapy compared to thalidomide monotherapy (see below), since immunomodulatory drugs do not appear to cause endothelial injury themselves.…”

Section: Thalidomidementioning

confidence: 99%

Thrombotic Complications of Myeloma Therapy

Zonder

2006

Hematology

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Patients with multiple myeloma are at relatively high baseline risk of developing thromboembolic events (TEE), usually deep vein thromboses. There are numerous contributing factors, among them certain treatment regimens that include thalidomide or related compounds such as lenalidomide combined with glucocorticoids and/or cytotoxic chemotherapy. The risk of developing TEE appears to be particularly high when these immunomodulatory agents are combined with anthracyclines as treatment of newly-diagnosed disease. Up-front combinations including thalidomide plus pulse dexamethasone and/or alkylating agents are associated with an intermediate risk, whereas the same regimens for relapsed/refractory myeloma seem to be associated with the lowest risk. Several different thromboprophylaxis strategies have been effective in lowering the risk of developing clots: daily aspirin (81-325 mg/day), full-intensity warfarin (INR 2-3), and prophylactic enoxaparin (40 mg SQ daily). Low, fixed-dose warfarin may also reduce the risk of TEE, but the data on this are disputable. None of these TEE prevention strategies have been prospectively compared head-to-head, so the choice often reflects physician and/or patient preferences. The available evidence upon which one might make such a decision is reviewed here.Individuals with multiple myeloma (MM) are at increased risk for developing thromboembolic events (TEE) compared to the general population. 1 The exact incidence is difficult to determine since reported TEE rates likely vary according to the level of diagnostic vigilance. For example, in one retrospective chart review at the Cleveland Clinic, which has an established imaging algorithm for evaluating patients with MM and monoclonal gammopathy of uncertain significance who have symptoms of a possible TEE, the reported rate was approximately 10%.1 In contrast, the rates documented in patients treated with melphalan-prednisone or dexamethasone as part of large multicenter studies without uniform algorithms for documenting TEE were 5% and 3%, respectively.2,3 It is likely the actual background incidence falls in the 5-10% range. Factors that have been suggested as contributory to the risk of TEE in people with MM include newly diagnosed disease status 4 ; immobility due to pain and/or surgery; indwelling central venous catheters; extrinsic venous compression by plasmacytomas; acquired abnormalities in platelet function, 5 clotting factors, 6 and the coagulation cascade 7-9 ; the presence of inherited factors such as Factor V Leiden; and treatment with immunomodulatory agents including thalidomide and lenalidomide. The risk of developing TEE during therapy with combination regimens containing thalidomide and lenalidomide will be discussed, followed by recommendations on prevention and treatment.

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Modification of thrombomodulin plasma levels in refractory myeloma patients during treatment with thalidomide and dexamethasone

Cited by 67 publications

References 14 publications

Thalidomide for treatment of multiple myeloma: 10 years later

Thalidomide for treatment of multiple myeloma: 10 years later

Systematic review to establish the safety profiles for direct and indirect inhibitors of p38 Mitogen-activated protein kinases for treatment of cancer

Thrombotic Complications of Myeloma Therapy

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