Ph-negative myeloproliferative diseases with thrombocythemia in the context of Thromboreductin^® treatment, data from registry 2013

Česká verzia

Authors: Miroslav Penka ¹; Jiří Schwarz ²; Petra Ovesná ³; Libor Červinek ⁴; Petr Dulíček ⁵ ; Dagmar Pospíšilová ⁶; Jarmila Kissová ¹; Tomáš Pavlík ³; Kolektiv České Pracovní Skupiny Pro Ph-Negativní Myeloproliferativní Onemocnění (czemp)
Authors place of work: Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Miroslav Penka, CSc. ¹; Ústav hematologie a krevní transfuze Praha, ředitel prof. MUDr. Petr Cetkovský, Ph. D., MBA ²; Institut biostatistiky a analýz MU Brno, ředitel doc. RNDr. Ladislav Dušek, CSc. ³; Interní hematologická a onkologická klinika LF MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Mayer, CSc. ⁴; IV. interní hematologická klinika LF UK a FN Hradec Králové, přednosta doc. MUDr. Pavel Žák, CSc. ⁵; Dětská klinika LF UP a FN Olomouc, přednosta prof. MUDr. Vladimír Mihál, Ph. D. ⁶
Published in the journal: Vnitř Lék 2014; 60(Suppl 2): 58-68
Category: 70th Birthday - prof. MUDr. Jiří Vorlíček, CSc.

a kolektiv České pracovní skupiny pro Ph-negativní myeloproliferativní onemocnění (CZEMP)

Summary

Czech Working Group for Ph-negative Myeloproliferative diseases (CZEMP) recommends anagrelid (Thromboreductin^®) for the treatment of Ph-negative chronic myeloproliferative disease (MPO) with thrombocythemia accompanying. To evaluate the efficacy of this treatment, the patient registry with essential thrombocythemia and/or thrombocytosis accompanying other Ph-negative myeloproliferative diseases was established. The beginnings of data collection go back to 2001, registry itself is maintained from 2005 and the aim is to archive the medical records with detailed physical and laboratory examination, safety patient profile included. The longest follow-up monitors 150 months period. Registry database contained 1,325 patients in the end of 2013, with an annual increase of anagrelid therapy as a drug of first choice in accordance with CZEMP guidelines approved by the Czech Society of Hematology of Czech Medical Association of J. E. Purkyne. Indication criteria contribute to this trend as anagrelid is the first choice agent in 65 years old patients, instead previous 60 years of age. Often, we can observe the combined treatment, especially, in older patients and in patients with primary myelofibrosis and polycythemia vera. There have been founded 543 thrombotic events in 413 patients and 63 bleeding events in 58 patients of study group by the end of 2013. During treatment, thrombosis was diagnosed 225 times in 171 patients and bleeding was observed 139 times in 104 patients. The therapeutic response is achieved after 3 months in 77% and after 6 months in 83% of subjects, but after 12 months, the treatment still fails in 12,5% of patients. It might be caused by slow titration of Thromboreductin^®. One of the most important indicators of treatment success is the effect on clinical symptoms presentation, especially the occurrence of thrombotic events. The proof of a good treatment efficacy is demonstrated by 1.8 fold decrease in arterial thrombosis, more than 1.5 fold decrease in microvascular thrombosis and even 6.2 fold decrease in venous thromboembolism events. Bleeding is observed in about double more patients in comparison to the period before inclusion in the systematic monitoring, but the bleedings are clinically insignificant.

Key words:
anagrelid (Thromboreductin^®) – Ph-myeloproliferative diseases – registry – thrombosis

Zdroje

1. Barbui T, Barosi G, Grossi A et al. Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Hematology, the Italian Society of Experimental Hematology and Italian Group for Bone Marrow Transplantation. Haematologica 2004; 89(2): 215–232.

2. Barbui T, Thiele J, Passamonti F et al Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol 2011; 29(23): 3179–3184.

3. Barbui T. Development of a new multiple variables model to predict thrombosis in Essential Thrombocythemia. ESH International Conference on Myeloproliferative Neoplasma Vienna, Austria, October 4–6, 2012.

4. Brière JB. Essential thrombocythemia. Orphanet J Rare Dis 2007; 2: 3. Dostupné z WWW: <http://www.ojrd.com/content/2/1/3>.

5. Cortelazzo S, Finazzi G, Ruggeri M et al. Hydoxyurea for patients with Essential Thrombocythemia and a high risk of thrombosis. N Engl J Med 1995; 332(17): 1132–1136.

6. Elliott MA, Tefferi A. Interferon-alfa therapy in Polycythemia Vera and essential Thrombocythemia. Semin Thromb Hemost 1997; 23(5): 463–472.

7. Finazzi G, Barbui T. Risk-adapted therapy in essential trombocythemia and polycythemia vera. Blood Rev 2005; 19(5): 243–252.

8. Fruchtman SM, Petitt RM, Gilbert HS et al. Anagrelide Study Group: Anagrelide: analysis of long-term efficacy, safety and leukemogenic potential in myeloproliferative disorders. Leuk Res 2005; 29(5): 481–491.

9. Gangat N, Wolanskyj AP, Schwager SM et al. Leukocytosis at Diagnosis and the Risk of Subsequent Thrombosis in Patients With Low-Risk Essential Thrombocythemia an Polycythemia Vera. Cancer 2009; 115(24): 5740–5745.

10. Gisslinger H, Gotic M, Holowiecki J et al. ANAHYDRET Study Group. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood 2013; 121(10): 1720–1728.

11. Hoffman R, Prchal JT, Samuelson S et al. Philadelphia chromosome-negative myeloproliferative disorders: biology and treatment. Biol Blood Marrow Transplant 2007; 13(1 Suppl 1): S64-S72.

12. Jaffe ES, Harris NL, Stein H et al. World health organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC Press: Lyon 2001.

13. Kaushansky K. The chronic myeloproliferative disorders and mutation of JAK2: Damesek´s 54 year old speculation comes of age. Best Pract Res Clin Haematol 2007; 20(1): 5–12.

14. Kissová J, Ovesná P, Penka M et al. Second malignancies in philadelphia-negative myeloproliferative neoplasms-single-center experience. Anticancer Res 2014; 34(5): 2489–2496.

15. Klampfl T, Gisslinger H, Harutyunyan AS et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013; 369(25): 2379–2390.

16. Kralovics R, Passamonti F, Buser AS et al. A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders. N Engl J Med 2005; 352(17): 1779–1790.

17. Kralovics R, Skoda RC. Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders. Blood Rev 2005; 19(1): 1–13.

18. Landolfi R, Rocca B, Patrono C Bleeding and thrombosis in myeloproliferative disorders: mechanism and treatment. Crit Rev Oncol Hematol 1995; 20(3): 203–222.

19. 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): 114–124.

20. Michiels JJ, Kutti J, Stark P et al. Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis. Neth J Med 1999; 54(2): 46–62.

21. Michiels JJ, Barbui T, Finazzi G et al. Diagnosis and treatment of Polycythemia Vera and possible future study designs of the PVSG. Leuk Lymphoma 2000; 36(3–4): 239–253.

22. Michiels JJ, Thiele J Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera and idiopathic myelofibrosis (agnogenic myeloid metaplasia). Int J Hematol 2002; 76(2): 133–145.

23. Michiels JJ, DeRaeve H, Hebeda K et al. WHO bone marrow features and European clinical, molecular, and pathological (ECMP) criteria for the diagnosis of myeloproliferative disorders. Leukemia Res 2007; 31(8): 1031–1038.

24. Murphy S, Peterson P, Iland H et al. Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Semin Hematol 1997; 34(1): 29–39.

25. Passamonti F, Rumi E, Arcaini L et al. Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica 2008; 93(11): 1645–1651.

26. Penka M, Schwarz J, Pytlík R et al. Doporuèený postup diagnostiky a terapie esenciální trombocytemie a trombocytemie provázející jiné myeloproliferativní choroby. Vnitř Lék 2005; 51(6): 741–751.

27. Penka M, Schwarz J, Pavlík T et al. Esenciální trombocytemie a další myeloproliferace s trombocytemií v údajích registru pacientů léčených Thromboreductinem^® do konce roku 2007. Vnitř Lék 2008; 54(6): 775–782.

28. Penka M, Schwarz J, Pavlík T et al. Výsledky léčby nemocných s esenciální trombocytemií a dalšími myeloproliferacemi provázenými trombocytemií – zpráva z registru pacientů léčených Thromboreductinem. Vnitř Lék 2009; 55(11): 1–12.

29. Penka M, Schwarz J, Ovesná P et al. Esenciální trombocytemie a jiné myeloproliferace s trombocytemií léčené Thromboreductinem. Výstupy z databáze Registru k prvnímu čtvrtletí roku 2010. Vnitř Lék 2010; 56(6): 503–512.

30. Penka M, Schwarz J, Ovesná P et al. kolektiv České pracovní skupiny pro myeloproliferativní choroby (CZEMP): Účinnost léčby anagrelidem u nemocných s Ph-negativními myeloproliferativními chorobami: ovlivnění výskytu trombózy ve výstupech Registru pacientů s diagnózou esenciální trombocytemie a trombocytemie provázející jiné myeloproliferativní onemocnění léčených Thromboreductinem^® ke konci roku 2012. Vnitř Lék 2013; 59(6): 516–531.

31. Penka M, Schwarz J, Ovesná P et al. kolektiv České pracovní skupiny pro myeloproliferativní choroby (CZEMP) Shrnutí doporučení České pracovní skupiny pro Ph-negativní myeloproliferativní onemocnění (CZEMP) České hematologické společnosti ČLS JEP pro diagnózu a terapii BCR/AB“ – negativních myeloproliferací. Vnitř Lék 2012; 58(2): 163–168.

32. Petrides PE. Anagrelid: decade of clinical experiences with its use for the treatment of primary thrombocythaemia. Expert Opin Pharmacother 2004; 5(8): 1781–1798.

33. Puigdecanet E, Spinet B, Villa O et al. Detection of abnormalities of PRV-1, TPO, and c-MPL genes detected by fluorescence in situ hybridization in essencial thrombocythemia. Cancer Genet Cytogenet 2006; 167(1): 39–42.

34. Rumi E, Pietra D, Ferretti V et al. Associazione Italiana per la Ricerca sul Cancro Italiano Malattie Myeloproliferative investigators. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 2014; 123(10): 1544–1551.

35. Reilly JT. Current treatment practices for essential thrombocythemia: survey results from European hematologist/oncologists. Hematology 2012; 17(4): 187–192.

36. Schwarz J, Hrachovinova I, Vorlova Z et al. Thromboembolism in thrombocythemia patients with an additional thrombophilic state. Hematol J 2004; 5(Suppl 2): S321. Abstract 974.

37. Schwarz J, Penka M, Doubek M et al. JAK2 mutation and an additional thrombophilic state are major prothrombotic risk factors in myeloproliferations with thrombocythemia – data from a registry of anagrelide-treated patients. 13th Congress of the European Hematology Association, Kopenhagen, Denmark, June 12–15, 2008. Haematologica – Hematol J 2008; 93(Suppl 1). Abstract 0144.

38. Schwarz J, Penka M, Campr V et al. Diagnostika a léčba bcr/abl-negativních myeloproliferativních onemocnění – principy a východiska CZEMP. Vnitř Lék 2011; 57(2): 189–213.

39. Silverstein MN, Tefferi A. Treatment of Essential Thrombocythemia with anagrelid. Semin Hematol 1999; 36(1 Suppl 2): S23-S25.

40. Steurer M, Gastl G, Jedrzejczak W et al. Anagrelide for Thrombocytosis in myeloproliferative disorders: a prospective study to assess efficacy and adverse event profile. Cancer 2004; 101(10): 2239–2246.

41. Thiele J, Kvasnicka HM, Vardiman J. Bone marrow histopathology in the diagnosis of chronic myeloproliferative disorders: a forgotten pearl. Best Pract Res Clin Haematol 2006; 19(3): 413–437.

42. Tefferi A, Thiele J, Orazi A et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 2007; 110(4): 1092–1097.

43. Tsimberidou MA, Colburn DE, Welch MA et al. Anagrelide and imatinib mesylate combination therapy in patients with chronic myeloproliferative disorders. Cancer Chemother Pharmacol 2003; 52(3): 229–234.

44. Vianello F, Battisti A, Cerlla G et al. Defining the Thrombotic Risk in Patients with Myeloproliferatove Neoplams. Scientific World Journal 2011; 11: 1131–1137.