Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Myeloma

Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma

Abstract

The incidence of venous thromboembolism (VTE) is more than 1‰ 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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ . Trends in the incidence of deep vein thrombosis and pulmonary embolism. A 25-year population-based study. Arch Intern Med 1998; 158: 585–593.

    CAS  Google Scholar 

  2. Sallah S, Wan JY, Nguyen NP . Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost 2002; 87: 575–579.

    CAS  Google Scholar 

  3. Blom JW, Doggen CJ, Osanto S, Rosendaal FR . Malignancy, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293: 715–722.

    CAS  Google Scholar 

  4. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ . Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 1999; 159: 445–453.

    CAS  Google Scholar 

  5. Samama MM . An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med 2000; 160: 3415–3420.

    CAS  Google Scholar 

  6. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ . Risk factors for deep vein thrombosis and pulmonary embolism. Arch Intern Med 2000; 160: 809–815.

    CAS  Google Scholar 

  7. Heit JA, O'Fallon WM, Petterson TM, Lohse CM, Silverstein MD, Mohr DN et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism. Arch Intern Med 2002; 162: 1245–1248.

    Google Scholar 

  8. Ageno W, Squizzato A, Garcia D, Imberti D . Epidemiology and risk factors of venous thromboembolism. Semin Thromb Hemost 2006; 32: 651–658.

    Google Scholar 

  9. Bauer KA . The thrombophilias: well-defined risk factors with uncertain therapeutic implications. Ann Intern Med 2001; 135: 367–373.

    CAS  Google Scholar 

  10. Bick RL . Cancer-associated thrombosis. N Engl J Med 2003; 349: 109–111.

    CAS  Google Scholar 

  11. Prandoni P, Falanga A, Piccioli A . Cancer and venous thromboembolism. Lancet Oncol 2005; 6: 401–410.

    Google Scholar 

  12. Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with mode-negative breast cancer who have estrogenreceptor-positive tumors. N Engl J Med 1989; 320: 479–484.

    CAS  Google Scholar 

  13. Fisher B, Dignam J, Wolmark N, DeCillis A, Emir B, Wickerham DL et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor positive breast cancer. J Natl Cancer Inst 1997; 89: 1673–1682.

    CAS  Google Scholar 

  14. White RH, Zhou H, Romano PS . Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost 2003; 90: 446–455.

    CAS  Google Scholar 

  15. Bona RD . Thrombotic complications of central venous catheters in cancer patients. Semin Thromb Haemost 1999; 25: 147–155.

    CAS  Google Scholar 

  16. Bern MM, Lokich JJ, Wallach SR, Bothe Jr A, Benotti PN, Arkin CF et al. Very low doses of warfarin can prevent thrombosis in central venous catheters: a randomized prospective trial. Ann Intern Med 1990; 112: 423–428.

    CAS  Google Scholar 

  17. Monreal M, Alastrue A, Rull M, Mira X, Muxart J, Rosell R et al. Upper extremity deep venous thrombosis in cancer patients with venous access devices-prophylaxis with low molecular weight heparin (Fragmin). Thromb Haemost 1996; 75: 251–253.

    CAS  Google Scholar 

  18. Verso M, Agnelli G . Venous thromboembolism associated with long term use of central venous catheters in cancer patients. J Clin Oncol 2003; 21: 3665–3675.

    Google Scholar 

  19. FDA Alert. Information For Healthcare Professional: Eyrthropoiesis Stimulating Agents (ESA) [Aranesp (Darbopoietin), Epogen (Epoietin Alfa), and Procrit (Epoietin Alfa)]. Food and Drug Administration: Rockville, MD, March 9, 2007. Accessed May 25, 2007, at http://www.fda.gov/cder/drug/InfoSheets/HCP/RHE2007HCP.htm.

  20. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M et al. Correction of anemia with epoietin alfa in chronic kidney disease. N Engl J Med 2006; 355: 2085–2098.

    CAS  Google Scholar 

  21. Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355: 2071–2084.

    CAS  Google Scholar 

  22. Sallah S, Husain A, Wan J, Vos P, Nguyen NP . The risk of venous thromboembolic disease in patients with monoclonal gammopathy of undetermined significance. Ann Oncol 2004; 15: 1490–1494.

    CAS  Google Scholar 

  23. Srkalovic G, Cameron MG, Rybicki L, Deitcher SR, Kattke-Marchant K, Hussein MA . Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer 2004; 101: 558–566.

    Google Scholar 

  24. Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR, Eastern Cooperative Oncology Group. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: A clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006; 24: 431–436.

    CAS  Google Scholar 

  25. Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006; 367: 825–831.

    CAS  Google Scholar 

  26. Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomized trial. Lancet 2007; 370: 1209–1218.

    CAS  Google Scholar 

  27. Zangari M, Saghafifar F, Mehta P, Barlogie B, Fink L, Tricot G . The blood coagulation mechanism in multiple myeloma. Semin Thromb Hemost 2003; 29: 275–282.

    CAS  Google Scholar 

  28. Fox EA, Kahn SR . The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost 2005; 94: 362–365.

    CAS  Google Scholar 

  29. Auwerda JJA, Sonneveld P, de Maat MPM, Leebeek FWG . Prothromboic coagulation abnormalities in patients with newly diagnosed multiple myeloma. Haematologica 2007; 92: 279–280.

    Google Scholar 

  30. Rajkumar SV, Gertz MA, Lacy MQ, Dispenzieri A, Fonseca R, Geyer SM et al. Thalidomide as initial therapy for early-stage myeloma. Leukemia 2003; 17: 775–779.

    CAS  Google Scholar 

  31. Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R . Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 2003; 21: 16–19.

    CAS  Google Scholar 

  32. Barlogie B, Desikan R, Eddlemon P, Spencer T, Zeldis J, Munshi N et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001; 98: 492–494.

    CAS  Google Scholar 

  33. Neben K, Moehler T, Benner A, Kraemer A, Egerer G, Ho AD et al. Dose-dependent effect of thalidomide on overall survival in relapsed multiple myeloma. Clin Cancer Res 2002; 8: 3377–3382.

    CAS  Google Scholar 

  34. Schey SA, Cavenagh J, Johnson R, Child JA, Oakervee H, Jones RW . An UK myeloma forum phase II study of thalidomide; long term follow-up and recommendations for treatment. Leuk Res 2003; 27: 909–914.

    CAS  Google Scholar 

  35. Cavo M, Zamagni E, Tosi P, Cellini C, Cangini D, Tacchetti P et al. First-line therapy with thalidomide and dexamethasone in preparation for autologous stem cell transplantation for multiple myeloma. Haematologica 2004; 89: 826–831.

    CAS  Google Scholar 

  36. Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002; 20: 4319–4323.

    CAS  Google Scholar 

  37. Anagnostopoulos A, Weber D, Rankin K, Delasalle K, Alexanian R . Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 2003; 121: 768–771.

    CAS  Google Scholar 

  38. Palumbo A, Bertola A, Falco P, Rosato R, Cavallo F, Giaccone L et al. Efficacy of low-dose thalidomide and dexamethasone as first salvage regimen in multiple myeloma. Hematol J 2004; 5: 318–324.

    CAS  Google Scholar 

  39. Dimopoulos MA, Anagnostopoulos A, Terpos E, Repoussis P, Zomas A, Katodritou E et al. Primary treatment with pulsed melphalan, dexamethasone and thalidomide for elderly symptomatic patients with multiple myeloma. Haematologica 2006; 91: 252–254.

    CAS  Google Scholar 

  40. Offidani M, Corvatta L, Marconi M, Olivieri A, Catarini M, Mele A et al. Thalidomide plus oral melphalan compared with thalidomide alone for advanced multiple myeloma. Hematol J 2004; 5: 312–317.

    CAS  Google Scholar 

  41. Osman K, Comenzo R, Rajkumar SV . Deep venous thrombosis and thalidomide therapy for multiple myeloma. N Engl J Med 2001; 344: 1951.

    CAS  Google Scholar 

  42. Schutt P, Ebeling P, Buttkereit U, Brandhorst D, Opalka B, Poser M et al. Thalidomide in combination with vincristine, epirubicin and dexamethasone (VED) for previously untreated patients with multiple myeloma. Eur J Haematol 2005; 74: 40–46.

    CAS  Google Scholar 

  43. Zervas K, Dimopoulos MA, Hatzicharissi E, Anagnostopoulos A, Papaioannou M, Mitsouli Ch et al. Primary treatment of multiple myeloma with thalidomide, vincristine, liposomal doxorubicin and dexamethasone (T-VAD doxil): a phase II multicenter study. Ann Oncol 2004; 15: 134–138.

    CAS  Google Scholar 

  44. Baz R, Li L, Kottke-Marchant K, Srkalovic G, McGowan B, Yiannaki E et al. The role of aspirin in the prevention of thrombotic complications of thalidomide and anthracycline-based chemotherapy for multiple myeloma. Mayo Clin Proc 2005; 80: 1568–1574.

    CAS  Google Scholar 

  45. Sidra G, Williams CD, Russell NH, Zaman S, Myers B, Byrne JL . Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed myeloma. Haematologica 2006; 91: 862–863.

    CAS  Google Scholar 

  46. Wu P, Davies FE, Horton C, Jenner MW, Krishnan B, Alvares CL et al. The combination of cyclophosphomide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide–vincristine–doxorubicin–methylprednisolone as induction chemotherapy prior to autologous transplantation for multiple myeloma: a case-matched analysis. Leuk Lymphoma 2006; 47: 2335–2338.

    CAS  Google Scholar 

  47. Dimopoulos MA, Hamilos G, Zomas A, Gika D, Efstathiou E, Grigoraki V et al. Pulsed cyclophosphamide, thalidomide and dexamethasone: an oral regimen for previously treated patients with multiple myeloma. Hematol J 2004; 5: 112–117.

    CAS  Google Scholar 

  48. Garcia-Sanz R, Gonzalez-Porras JR, Hernandez JM, Polo-Zarzuela M, Sureda A, Barrenetxea C et al. The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma. Leukemia 2004; 18: 856–863.

    CAS  Google Scholar 

  49. Kropff MH, Lang N, Bisping G, Dominé N, Innig G, Hentrich M et al. Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Br J Haematol 2003; 122: 607–616.

    CAS  Google Scholar 

  50. Suvannasankha A, Fausel C, Juliar BE, Yiannoutsos CT, Fisher WB, Ansari RH et al. Final report of toxicity and efficacy of a phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with relapsed or refractory multiple myeloma: a Hoosier Oncology Group Trial, HEM01-21. Oncologist 2007; 12: 99–106.

    CAS  Google Scholar 

  51. Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354: 1021–1030.

    CAS  Google Scholar 

  52. Zangari M, Siegel E, Barlogie B, Anaissie E, Saghafifar F, Fassas A et al. Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy. Blood 2002; 100: 1168–1171.

    CAS  Google Scholar 

  53. Lee C-K, Barlogie B, Munshi N, Zangari M, Fassas A, Jacobson J et al. DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol 2003; 21: 2732–2739.

    CAS  Google Scholar 

  54. Zonder JA . Thrombotic complications of myeloma therapy. Hematology Am Soc Hematol Educ Program 2006; 1: 348–355.

    Google Scholar 

  55. Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002; 100: 3063–3067.

    CAS  Google Scholar 

  56. Zangari M, Tricot G, Zeldis J, Eddlemon P, Saghafifar F, Barlogie B . Results of phase I study of CC-5013 for the treatment of multiple myeloma (MM) patients who relapse after high dose chemotherapy. Blood 2001; 98: 775a (abstract [3226]).

    Google Scholar 

  57. Zonder JA, Barlogie B, Durie BG, McCoy J, Crowley J, Hussein MA . Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis. Blood 2006; 108: 403.

    CAS  Google Scholar 

  58. Rajkumar SV, Jacobus S, Callander N, Fonseca R, Vesole D, Williams M et al. Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2007; 25: 447s (abstract [8025]).

    Google Scholar 

  59. Dimopoulos MA, Spencer A, Attal M, Prince M, Harousseau J, Dmoszynska A et al. Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of a phase 3 study (MM-010). Blood 2005; 106: 6a (abstract [6]).

    Google Scholar 

  60. Weber D, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer E et al. Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): results of a North American phase III study (MM-009). J Clin Oncol 2006; 24: 427s (abstract [7521]).

    Google Scholar 

  61. Morgan GJ, Schey SA, Wu P, Srikanth M, Phekoo KJ, Jenner M et al. Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for myeloma patients. Br J Haematol 2007; 137: 268–269.

    Google Scholar 

  62. Richardson P, Schlossman R, Munshi N, Avigan D, Jagannath S, Alsina M et al. A phase 1 trial of lenalidomide (REVLIMID(R)) with bortezomib (VELCADE(R)) in relapsed and refractory multiple myeloma. Blood 2005; 106: 110a (abstract [365]).

    Google Scholar 

  63. Zangari M, Barlogie B, Thertulien R, Jacobson J, Eddleman P, Fink L et al. Thalidomide and deep vein thrombosis in multiple myeloma: risk factors and effect on survival. Clin Lymphoma 2003; 4: 32–35.

    CAS  Google Scholar 

  64. Galli M, Elice F, Crippa C, Comotti B, Rodeghiero F, Barbui T . Recombinant human erythropoietin and the risk of thrombosis in patients receiving thalidomide for multiple myeloma. Haematologica 2004; 89: 1141–1142.

    CAS  Google Scholar 

  65. Knight R, DeLap RJ, Zeldis JB . Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med 2006; 354: 2079–2080.

    CAS  Google Scholar 

  66. Cohen AT, Alikhan R, Arcelus JI, Bergmann JF, Haas S, Merli GJ et al. Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients. Thromb Haemost 2005; 94: 750–759.

    Google Scholar 

  67. Haas SK . Venous thromboembolic risk and its prevention in hospitalized medical patients. Semin Thromb Hemost 2002; 28: 577–584.

    Google Scholar 

  68. Dentali F, Douketis JD, Gianni M, Lim W, Crowther MA . Meta-anlaysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007; 146: 278–288.

    Google Scholar 

  69. Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med 1999; 341: 793–800.

    CAS  Google Scholar 

  70. Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Vaitkus PT, Goldhaber SZ, PREVENT Medical Thromboprophylaxis Study Group. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004; 110: 874–879.

    CAS  Google Scholar 

  71. Cohen AT, Davidson BL, Gallus AS, Lassen MR, Prins MH, Tomkowski W et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomized placebo controlled trial. BMJ 2006; 332: 325–329.

    CAS  Google Scholar 

  72. Mismetti P, Laporte-Simitsidis S, Tardy B, Cucherat M, Buchmuller A, Juillard-Delsart D et al. Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomized clinical trials. Thromb Haemost 2000; 83: 14–19.

    CAS  Google Scholar 

  73. Francis CW . Prophylaxis for thromboembolism in hospitalized medical patients. N Engl J Med 2007; 356: 1438–1444.

    CAS  Google Scholar 

  74. Geerts WH, Pineo GF, Heit JA, Berggvist D, Lassen MR, Colwell CW et al. Prevention of venous thromboembolism: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126: 338–400.

    Google Scholar 

  75. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy: III. reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. BMJ 1994; 308: 235–246.

    Google Scholar 

  76. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet 2000; 355: 1295–1302.

  77. Alikhan R, Cohen AT, Combe S, Samama MM, Desjardins L, Eldor A et al. Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study. Blood Coagul Fibrinolysis 2003; 12: 341–346.

    Google Scholar 

  78. Levine M, Hirsh J, Gent M, Arnold A, Warr D, Falanga A et al. Double-bind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 1994; 343: 886–889.

    CAS  Google Scholar 

  79. Taube J, Halsall D, Baglin T . Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood 2000; 96: 1816–1819.

    CAS  Google Scholar 

  80. Wang M, Weber D, Delasalle K, Alexanian R . Thalidomide–dexamethasone as primary therapy for advanced multiple myeloma. Am J Hematol 2005; 79: 194–197.

    CAS  Google Scholar 

  81. Minnema MC, Breitkreutz I, Auwerda JJ, van der Holt B, Cremer FW, van Marion AM et al. Prevention of venous thromboembolism with low molecular-weight heparin in patients with multiple myeloma treated with thalidomide and chemotherapy. Leukemia 2004; 18: 2044–2046.

    CAS  Google Scholar 

  82. Offidani M, Corvetta L, Piersantelli MN, Visani G, Alesiani F, Brunori M et al. Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma. Blood 2006; 108: 2159–2164.

    CAS  Google Scholar 

  83. Zangari M, Barlogie B, Anaissie E, Saghafifar F, Eddlemon P, Jacobson J et al. Deep vein thrombosis in patients with multiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation. Br J Haematol 2004; 126: 715–721.

    CAS  Google Scholar 

  84. Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005; 106: 4050–4053.

    CAS  Google Scholar 

  85. Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N et al. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma. J Clin Oncol 2007; 25: 4459–4465.

    CAS  Google Scholar 

  86. Baz R, Walker E, Karam MA, Choueiri TK, Jawde RA, Bruening K et al. Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Ann Oncol 2006; 17: 1766–1771.

    CAS  Google Scholar 

  87. Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C . Low-dose aspirin for the prevention for atherothrombosis. N Engl J Med 2005; 353: 2373–2383.

    CAS  Google Scholar 

  88. US Food and Drug Administration Web site. Thalidomide package insert. http://www.fda.gov/cder/foi/label/2006/021430s000,020785s031lbl.pdf. Accessed September 6 2006.

  89. US Food and Drug Administration Web site. Lenalidomide package insert. http://www.fda.gov/cder/foi/label/2006/021880s001.pdf. Accessed September 6 2006.

  90. Zangari M, Barlogie B, Lee CK, Tricot AE, Fassas A, Anaissie E et al. Protective effect of VELCADE® on thalidomide-associated deep vein thrombosis (DVT). Blood 2004; 104: 13a (abstract [4914]).

    Google Scholar 

  91. Cestac P, Bagheri H, Lapeyre-Mestre M, Sie P, Fouladi A, Maupas E et al. Utilisation and safety of low molecular weight heparins: prospective observational study in medical inpatients. Drug Saf 2003; 26: 197–207.

    CAS  Google Scholar 

  92. Nagge J, Crowther M, Hirsh J . Is impaired renal function a contraindication to the use of low-molecular-weight heparin? Arch Intern Med 2002; 162: 2605–2609.

    Google Scholar 

  93. Thromboembolic Risk Factors (THRIFT) Consensus Group. Risk of and prophylaxis for venous thromboembolism in hospital patients. BMJ 1992; 305: 567–574.

    Google Scholar 

  94. Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P . Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (Suppl 3): 483S–512S.

    CAS  Google Scholar 

  95. Lagerstedt CI, Olsson CB, Fagher BO, Oqvist BW, Albrechtsson U . Need for long term anticoagulant treatment in patients with symptomatic calf-vein thrombosis. Lancet 1985; 2: 515–518.

    CAS  Google Scholar 

  96. Moser KM, Fedullo PF, LittleJohn JK, Crawford R . Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis. JAMA 1994; 271: 223–225.

    CAS  Google Scholar 

  97. Bozlar U, Gaughen JR, Nambiar AP, Hagspiel KD . Imaging diagnosis of acute pulmonary embolism. Expert Rev Cardiovasc Ther 2007; 5: 519–529.

    Google Scholar 

  98. Baglin T, Luddington R, Brown K, Baglin C . Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet 2003; 362: 523–526.

    Google Scholar 

  99. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Martin Prins MB et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146–153.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to A Palumbo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Palumbo, A., Rajkumar, S., Dimopoulos, M. et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 22, 414–423 (2008). https://doi.org/10.1038/sj.leu.2405062

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2405062

Keywords

  • thrombosis
  • prophylaxis
  • risk factors
  • thalidomide
  • lenalidomide

This article is cited by

Search

Quick links