nach oben

Current Hematologic Malignancy Reports

Erschienen in:

01.12.2013 | Myeloproliferative Disorders (JJ Kiladjian, Section Editor)

Are MPNs Vascular Diseases?

verfasst von: Guido Finazzi, Valerio De Stefano, Tiziano Barbui

Erschienen in: Current Hematologic Malignancy Reports | Ausgabe 4/2013

Einloggen, um Zugang zu erhalten

Abstract

A high risk of arterial and venous thrombosis is the hallmark of chronic myeloproliferative neoplasms (MPNs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Clinical aspects, pathogenesis and management of thrombosis in MPN resemble those of other paradigmatic vascular diseases. The occurrence of venous thrombosis in atypical sites, such as the splanchnic district, and the involvement of plasmatic prothrombotic factors, including an acquired resistance to activated protein C, both link MPN to inherited thrombophilia. Anticoagulants are the drugs of choice for these complications. The pathogenic role of leukocytes and inflammation, and the high mortality rate from arterial occlusions are common features of MPN and atherosclerosis. The efficacy and safety of aspirin in reducing deaths and major thrombosis in PV have been demonstrated in a randomized clinical trial. Finally, the Virchow’s triad of impaired blood cells, endothelium and blood flow is shared both by MPN and thrombosis in solid cancer. Phlebotomy and myelosuppressive agents are the current therapeutic options for correcting these abnormalities and reducing thrombosis in this special vascular disease represented by MPN.

Tefferi A, Vainchenker W. Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol. 2011;29(5):573–82.PubMedCrossRef

Cross NC. Genetic and epigenetic complexity in myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program. 2011;208–14.

De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood. 1996;87:3531–44.PubMed

De Stefano V, Rossi E, Paciaroni K, Leone G. Screening for inherited thrombophilia: indications and therapeutic implications. Haematologica. 2002;87:1095–108.PubMed

Roemisch J, Gray E, Hoffmann JN, Wiedermann CJ. Antithrombin: a new look at the actions of a serine protease inhibitor. Blood Coagul Fibrinolysis. 2002;13:657–70.PubMedCrossRef

Bertina RM. The role of procoagulants and anticoagulants in the development of venous thromboembolism. Thromb Res. 2009;123 Suppl 4:S41–5.PubMedCrossRef

Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet. 1999;353:1167–73.PubMedCrossRef

Rossi E, Ciminello A, Za T, Betti S, Leone G, De Stefano V. In families with inherited thrombophilia the risk of venous thromboembolism is dependent on the clinical phenotype of the proband. Thromb Haemost. 2011;106:646–54.PubMedCrossRef

Sanson BJ, Simioni P, Tormene D, Moia M, Friederich PW, Huisman MV, et al. The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study. Blood. 1999;94:3702–6.PubMed

10.

Mahmoodi BK, Brouwer JL, Ten Kate MK, Lijfering WM, Veeger NJ, Mulder AB. A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin. J Thromb Haemost. 2010;8:1193–200.PubMedCrossRef

11.

Simioni P, Tormene D, Prandoni P, Zerbinati P, Gavasso S, Cefalo P, et al. Incidence of venous thromboembolism in asymptomatic family members who are carriers of factor V Leiden: a prospective cohort study. Blood. 2002;99:1938–42.PubMedCrossRef

12.

Coppens M, van de Poel MH, Bank I, Hamulyak K, van der Meer J, Veeger NJ, et al. A prospective cohort study on the absolute incidence of venous thromboembolism and arterial cardiovascular disease in asymptomatic carriers of the prothrombin 20210A mutation. Blood. 2006;108:2604–7.PubMedCrossRef

13.

Marchioli R, Finazzi G, Landolfi R, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005;23(10):2224–32.PubMedCrossRef

14.

Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353(1):33–45.PubMedCrossRef

15.

Gisslinger H, Gotic M, Holowiecki J, et al. Anagrelide compared to hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013;121(10):1720–8.PubMedCrossRef

16.

Barbui T, Carobbio A, Cervantes F, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood. 2010;115(4):778–82.PubMedCrossRef

17.

Gangat N, Wolanskyj AP, Tefferi A. Abdominal vein thrombosis in essential thrombocythemia: prevalence, clinical correlates, and prognostic implications. Eur J Haematol. 2006;77:327–33.PubMedCrossRef

18.

De Stefano V, Fiorini A, Rossi E, Za T, Farina G, Chiusolo P, et al. Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost. 2007;5:708–14.PubMedCrossRef

19.

• Smalberg JH, Arends LR, Valla DC, Kiladjian JJ, Janssen HL, Leebeek FW. Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis. Blood. 2012;120(25):4921–8. A recent and comprehensive meta-analysis of the important clinical association of MPN with splanchnic vein thrombosis (SVT), validating routine inclusion of JAK2V617F testing in the diagnostic workup of SVT patients. PubMedCrossRef

20.

Kiladjian JJ, Cervantes F, Leebeek FW, Marzac C, Cassinat B, Chevret S, et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood. 2008;111:4922–9.PubMedCrossRef

21.

Primignani M, Barosi G, Bergamaschi G, Gianelli U, Fabris F, Reati R, et al. Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology. 2006;44:1528–34.PubMedCrossRef

22.

Martinelli I, De Stefano V. Rare thromboses of cerebral, splanchnic and upper-extremity veins. A narrative review. Thromb Haemost. 2010;103:1136–44.PubMedCrossRef

23.

Dentali F, Galli M, Gianni M, et al. Inherited thrombophilic abnormalities and risk of portal vein thrombosis. A meta-analysis. Thromb Haemost. 2008;99:675–82.PubMed

24.

Marchetti M, Falanga A. Leukocytosis, JAK2V617F mutation, and hemostasis in myeloproliferative disorders. Pathophysiol Haemost Thromb. 2008;36(3–4):148–59.PubMed

25.

Marchetti M, Castoldi E, Spronk HM, et al. Thrombin generation and activated protein C resistance in patients with essential thrombocythemia and polycythemia vera. Blood. 2008;112(10):4061–8.PubMedCrossRef

26.

Arellano-Rodrigo E, Alvarez-Larrán A, Reverter JC, et al. Platelet turnover, coagulation factors, and soluble markers of platelet and endothelial activation in essential thrombocythemia: relationship with thrombosis occurrence and JAK2 V617F allele burden. Am J Hematol. 2009;84(2):102–8.PubMedCrossRef

27.

Brinkman HJ, Mertens K, van Mourik JA. Proteolytic cleavage of protein S during the hemostatic response. J Thromb Haemost. 2005;3(12):2712–20.PubMedCrossRef

28.

Dienava-Verdoold I, Marchetti MR, te Boome LC, et al. Platelet-mediated proteolytic down regulation of the anticoagulant activity of protein S in individuals with haematological malignancies. Thromb Haemost. 2012;107(3):468–76.PubMedCrossRef

29.

Robertson B, Urquhart C, Ford I, et al. Platelet and coagulation activation markers in myeloproliferative diseases: relationships with JAK2 V6I7 F status, clonality, and antiphospholipid antibodies. J Thromb Haemost. 2007;5(8):1679–85.PubMedCrossRef

30.

Alvarez-Larrán A, Arellano-Rodrigo E, Reverter JC, et al. Increased platelet, leukocyte, and coagulation activation in primary myelofibrosis. Ann Hematol. 2008;87(4):269–76.PubMedCrossRef

31.

Rosti V, Villani L, Riboni R, et al. Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation. Blood. 2013;121(2):360–8.PubMedCrossRef

32.

Sozer S, Fiel MI, Schiano T, Xu M, Mascarenhas J, Hoffman R. The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome. Blood. 2009;113(21):5246–9.PubMedCrossRef

33.

Carobbio A, Thiele J, Passamonti F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood. 2011;117(22):5857–9.PubMedCrossRef

34.

Lussana F, Caberlon S, Pagani C, Kamphuisen PW, Büller HR, Cattaneo M. Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idiopathic myelofibrosis: a systematic review. Thromb Res. 2009;124(4):409–17.PubMedCrossRef

35.

Ruggeri M, Gisslinger H, Tosetto A, et al. Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia. Am J Hematol. 2002;71(1):1–6.PubMedCrossRef

36.

Gisslinger H, Müllner M, Pabinger I, et al. Mutation of the prothrombin gene and thrombotic events in patients with polycythemia vera or essential thrombocythemia: a cohort study. Haematologica. 2005;90(3):408–10.PubMed

37.

De Stefano V, Za T, Rossi E, et al. Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia. Haematologica. 2009;94(5):733–7.PubMedCrossRef

38.

Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2_suppl):e419S–94S.PubMedCrossRef

39.

De Stefano V, Za T, Rossi E, et al. Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments. Haematologica. 2008;93(3):372–80.PubMedCrossRef

40.

Condat B, Pessione F, Hillaire S, et al. Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy. Gastroenterology. 2001;120:490–7.PubMedCrossRef

41.

Narayanan Menon KV, Shah V, Kamath PS. The Budd-Chiari syndrome. N Engl J Med. 2004;350:578–85.CrossRef

42.

•• Barbui T, Barosi G, Birgegard G, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European Leukemia. Net J Clin Oncol. 2011;29:761–70. Updated management recommendations for MPN patients provided by an expert consensus panel. CrossRef

43.

Libby P, Ridke PM, Maseri A. Inflamm Atheroscler Circ. 2002;105:1135–43.

44.

Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med. 2011;17:1410–22.PubMedCrossRef

45.

Falanga A, Marchetti M, Barbui T, Smith CW. Pathogenesis of thrombosis in essential thrombocythemia and polycythemia vera: the role of neutrophils. Semin Hematol. 2005;42(4):239–47.PubMedCrossRef

46.

Afshar-Kharghan V, Thiagarajan P. Leukocyte adhesion and thrombosis. Curr Opin Hematol. 2006;13(1):34–9.PubMedCrossRef

47.

Landolfi R, Di Gennaro L, Falanga A. Thrombosis in myeloproliferative disorders: pathogenetic facts and speculation. Leukemia. 2008;22:2020–8.PubMedCrossRef

48.

Falanga A, Marchetti M, Vignoli A, Balducci D, Barbui T. Leukocyte-platelet interaction in patients with essential thrombocythemia and polycythemia vera. Exp Hematol. 2005;33(5):523–30.PubMedCrossRef

49.

Barbui T, Carobbio A, Finazzi G, et al. Inflammation and thrombosis in essential thrombocythemia and polycythemia vera: different role of C-reactive protein and pentraxin 3. Haematologica. 2011;96(2):315–8.PubMedCrossRef

50.

Barbui T, Carobbio A, Rambaldi A, Finazzi G. Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: is leukocytosis a causative factor? Blood. 2009;114(4):759–63.PubMed

51.

Landolfi R, Di Gennaro L, Barbui T, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood. 2007;109(6):2446–52.PubMedCrossRef

52.

Wolanskyj AP, Schwager SM, McClure RF, Larson DR, Tefferi A. Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc. 2006;81(2):159–66.PubMedCrossRef

53.

Carobbio A, Antonioli E, Guglielmelli P, Vannucchi AM, Delaini F, Guerini V, et al. Leukocytosis and risk stratification assessment in essential thrombocythemia. J Clin Oncol. 2008;26(16):2732–6.PubMedCrossRef

54.

Palandri F, Polverelli N, Catani L, Ottaviani E, Baccarani M, Vianelli N. Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study. Ann Hematol. 2011;90(8):933–8.PubMedCrossRef

55.

Passamonti F, Rumi E, Pascutto C, Cazzola M, Lazzarino M. Increase in leukocyte count over time predicts thrombosis in patients with low-risk essential thrombocythemia. J Thromb Haemost. 2009;7(9):1587–9.PubMedCrossRef

56.

Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004;350(2):114–24.PubMedCrossRef

57.

Alvarez-Larrán A, Cervantes F, Pereira A, et al. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood. 2010;116(8):1205–10.PubMedCrossRef

58.

Pascale S, Petrucci G, Dragani A, et al. Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target. Blood. 2012;119(15):3595–603.PubMedCrossRef

59.

Tefferi A, Barbui T. Personalized management of essential thrombocythemia-application of recent evidence to clinical practice. Leukemia. 2013. doi:10.1038/leu.2013.99 [Epub ahead of print].

60.

Hasselbalch HC, Riley CH. Statins in the treatment of polycythaemia vera and allied disorders: an antithrombotic and cytoreductive potential? Leuk Res. 2006;30:1217–25.PubMedCrossRef

61.

Griner LN, McGraw KL, Johnson JO, List AF, Reuther GW. JAK2-V617F-mediated signalling is dependent on lipid rafts and statins inhibit JAK2-V617F-dependent cell growth. Br J Haematol. 2013;160:177–87.PubMedCrossRef

62.

Trousseau A. Phlegmasia alba dolens. Clin Med Hotel Dieu Paris. 1865;3:654–712.

63.

Falanga A, Russo L, Verzeroli C. Mechanisms of thrombosis in cancer. Thromb Res. 2013;131 Suppl 1:S59–62.PubMedCrossRef

64.

Lip GYH, Chin BSP, Blann AD. Cancer and the prothrombotic state. Lancet Oncol. 2002;3:27–34.PubMedCrossRef

65.

Prandoni P. Antithrombotic strategies in patients with cancer. Thromb Haemost. 1997;78:141–4.PubMed

66.

Virchow R. Gesammalte Abhandlungen zur Wissenschaftlichen Medtzin. Frankfurt: Medinger Sohn; 1856.

67.

Adams BD, Baker R, Lopez JA, Spencer S. Myeloproliferative disorders and the hyperviscosity syndrome. Hematol Oncol Clin North Am. 2010;24(3):585–602.PubMedCrossRef

68.

Turitto VT, Weiss HJ. Red blood cells: their dual role in thrombus formation. Science. 1980;207(4430):541–3.PubMedCrossRef

69.

De Grandis M et al. JAK2V617F activates Lu/BCAM-mediated red cell adhesion in polycythemia vera through an EpoR-independent Rap1/Akt pathway. Blood. 2013;121(4):658–65.PubMedCrossRef

70.

Arellano-Rodrigo E, Alvarez-Larrán A, Reverter JC, Villamor N, Colomer D, Cervantes F. Increased platelet and leukocyte activation as contributing mechanisms for thrombosis in essential thrombocythemia and correlation with the JAK2 mutational status. Haematologica. 2006;91(2):169–75.PubMed

71.

Falanga A, Marchetti M, Vignoli A, et al. V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules. Exp Hematol. 2007;35(5):702–11.PubMedCrossRef

72.

Maugeri N, Malato S, Femia EA, et al. Clearance of circulating activated platelets in polycythemia vera and essential thrombocythemia. Blood. 2011;118(12):3359–66.PubMedCrossRef

73.

Jensen MK, de Nully BP, Lund BV, Nielsen OJ, Hasselbalch HC. Increased platelet activation and abnormal membrane glycoprotein content and redistribution in myeloproliferative disorders. Br J Haematol. 2000;110(1):116–24.PubMedCrossRef

74.

Panova-Noeva M, Marchetti M, Spronk HM, et al. Platelet-induced thrombin generation by the calibrated automated thrombogram assay is increased in patients with essential thrombocythemia and polycythemia vera. Am J Hematol. 2011;86(4):337–42.PubMedCrossRef

75.

Treliński J, Wierzbowska A, Krawczyńska A, et al. Plasma levels of angiogenic factors and circulating endothelial cells in essential thrombocythemia: correlation with cytoreductive therapy and JAK2-V617F mutational status. Leuk Lymphoma. 2010;51(9):1727–33.PubMed

76.

Belotti A, Elli E, Speranza T, Lanzi E, Pioltelli P, Pogliani E. Circulating endothelial cells and endothelial activation in essential thrombocythemia: results from CD146+ immunomagnetic enrichment–flow cytometry and soluble E-selectin detection. Am J Hematol. 2012;87(3):319–20.PubMedCrossRef

77.

Alonci A, Allegra A, Bellomo G, et al. Evaluation of circulating endothelial cells, VEGF and VEGFR2 serum levels in patients with chronic myeloproliferative diseases. Hematol Oncol. 2008;26(4):235–9.PubMedCrossRef

78.

Friedenberg WR, Roberts RC, David DE. Relationship of thrombohemorrhagic complications to endothelial cell function in patients with chronic myeloproliferative disorders. Am J Hematol. 1992;40(4):283–9.PubMedCrossRef

79.

Cella G, Marchetti M, Vianello F, et al. Nitric oxide derivatives and soluble plasma selectins in patients with myeloproliferative neoplasms. Thromb Haemost. 2010;104(1):151–6.PubMedCrossRef

80.

•• Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22–33. The most recent randomized clinical trial on patients with polycythemia vera demonstrating the clinical benefit of a strict control of hematocrit. PubMedCrossRef

81.

Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995;332(17):1132–6.PubMedCrossRef

82.

Maugeri N, Giordano G, Petrilli MP, et al. Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug? J Thromb Haemost. 2006;4(12):2593–8.PubMedCrossRef

83.

Finazzi G, Ruggeri M, Rodeghiero F, Barbui T. Second malignancies in patients with essential thrombocythaemia treated with busulphan and hydroxyurea: long-term follow-up of a randomized clinical trial. Br J Haematol. 2000;110(3):577–83.PubMedCrossRef

84.

• Björkholm M, Derolf AR, Hultcrantz M, et al. Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms. J Clin Oncol. 2011;29(17):2410–5. A convincing demonstration of the negligible, if any, leukemogenic risk of hydoxyurea in the treatment of MPN. PubMedCrossRef

85.

Finazzi G, Caruso V, Marchioli R, et al. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood. 2005;105(7):2664–70.PubMedCrossRef

86.

Silver RT, Kiladjian JJ, Hasselbalch HC. Interferon and the treatment of polycythemia vera, essential thrombocythemia and myelofibrosis. Expert Rev Hematol. 2013;6(1):49–58.PubMedCrossRef

87.

Kiladjian JJ, Cassinat B, Chevret S, et al. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood. 2008;112(8):3065–72.PubMedCrossRef

88.

Quintás-Cardama A, Kantarjian H, Manshouri T, et al. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol. 2009;27(32):5418–24.PubMedCrossRef

89.

Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807.PubMedCrossRef

90.

Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787–98.PubMedCrossRef

Titel: Are MPNs Vascular Diseases?
verfasst von: Guido Finazzi
Valerio De Stefano
Tiziano Barbui
Publikationsdatum: 01.12.2013
Verlag: Springer US
Erschienen in: Current Hematologic Malignancy Reports / Ausgabe 4/2013
Print ISSN: 1558-8211
Elektronische ISSN: 1558-822X
DOI: https://doi.org/10.1007/s11899-013-0176-z

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Are MPNs Vascular Diseases?

Abstract

Neu im Fachgebiet Onkologie

Blutdrucksenkung könnte Uterusmyome verhindern

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Update Onkologie

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2013

Molecular Classification of Myeloproliferative Neoplasms—Pros and Cons

Multiple Myeloma: Defining the High-Risk Patient and Determining the Optimal Treatment Strategy

Genetic Basis of MPN: Beyond JAK2-V617F

Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: What Place, If Any?

New Approaches to Smoldering Myeloma

There’s Risk, and Then There’s RISK: The Latest Clinical Prognostic Risk Stratification Models in Myelodysplastic Syndromes

Neu im Fachgebiet Onkologie

Blutdrucksenkung könnte Uterusmyome verhindern

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Update Onkologie