Essential thrombocythaemia and other myeloproliferative disorders with thrombocythaemia treated with Thromboreductin. A report from the database of Register for the 1st quarter of 2010

Česká verzia

Authors: M. Penka ¹; J. Schwarz ²; P. Ovesná ³; A. Hluší ⁴; Z. Kořístek ⁵; M. Doubek ⁵; P. Ďulíček ⁶; D. Pospíšilová ⁷; J. Kissová ¹; A. Buliková ¹; T. Pavlík ³; Kolektiv České Pracovní Skupiny Pro Myeloproliferativní Choroby (czemp)
Authors place of work: Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Miroslav Penka, CSc. 2Ústav hematologie a krevní transfuze Praha, ředitel prof. MU Dr. Marek Trněný, CSc. 3Institut biostatiky a analýz Lékařské a Přírodovědecké fakulty M ¹
Published in the journal: Vnitř Lék 2010; 56(6): 503-512
Category: Original Contributions

Summary

In the Czech Republic, anagrelid is used according to the recommendations of the Czech Working Group on Myeloproliferative Disorders for treatment of thrombocythaemias associated with chronic myeloproliferative disorders – mainly essential thrombocythaemia and, regularly, reports are being presented from the Register of Patients Treated with Thromboreductin^®, most recently last year (Vnitř Lék 2009; 55: I– XII). The Register commenced in 2005 and from then it aims to determine detailed clinical and laboratory profiles of the patients. The structure of the Register has changed significantly in the course of its existence, reflecting the reports from each of the analyses conducted so far. Also, the data entry in the database improves every year and it reaches 97% on some of the items. The longest evaluation period in some of the patients is 108 months. By April 2010, the Register database contained data on 717 patients. Of these, 672 patients with the diagnosis of a Ph‑ negative chronic myeloproliferative disorder were evaluated. This year’s analysis included the patients with essential thrombocythaemia, polycythaemia vera and primary myelofibrosis only. The analysis included 418 women and 254 men with median age of 50 years. Unlike the first years, 2/ 3 of the current sample are non pretreated patients, meaning that the patients reach the specialized centres early in their treatment. Also, patients, and the older patients in particular, are more frequently treated with combined regimens including Thromboreductin^®. We increasingly observe hypertension as one of the monitored risk factors preceding the disease and laboratory parameters show JAK2 mutation in more than a half of patients while some form of thrombotic diathesis is found in the anamnesis of 7– 10% of patients. Some bleeding is observed in 1– 5% of the registered patients. In comparison to the previous years, this is a decrease in the prevalence of clinical symptoms prior to the disease onset; this is very likely associated with an earlier patient diagnosis within the asymptomatic phase of the disease. Therapeutically, we achieve a fast treatment response but there still are 16.3% of sufficient after one year of treatment. Thromboreductin^® dose is increasing but even in this group it does not exceeds the mean of 2.38 mg per 24 hours. Complications are observed in 6.2% of patients in the first year of therapy, and of these, thrombotic events in about 2.5% and (small) bleeding complications in 4% of patients. The data suggest that we still do not reach treatment response in a certain proportion of patients after a year of their therapy. Even though the care results from the analysed data improve every year, the Register helps to uncover some issues that still remain, such as treatment intensification and other treatment modifications.

Key words:
essential thrombocytopenia – myeloproliferative disorders – anagrelid (Thromboreductin^®) – Register – JAK2 mutation – thrombophilia

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 the Italian Group for Bone Marrow Transplantation. Haematologica 2004; 89: 215– 232.

2. Brière JB. Essential thrombocythemia. Orphanet J Rare Dis 2007; 2– 3:1– 17.

3. 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: 1132– 1136.

4. Costello R, O’Callaghan TO, Sébahoun G. Traitement de la thrombocythémie essentielle. Rev Med Interne 2005; 26: 947– 955.

5. Elliott MA, Tefferi A. Interferon‑alpha therapy in polycythemia vera and essential thrombocythemia. Semin Thromb Hemost 1997; 23: 463– 472.

6. Fruchtman SM, Petitt RM, Gilbert HS et al. Anagrelid: analysis of long‑term efficacy, safety and leukemogenic potential in myeloproliferative disorders. Leuk Res 2005; 29: 481– 491.

7. Gisslinger H, Kralovics R, Gotic M et al. Non‑ inferiority of anagrelide compared to hydroxyurea in newly diagnose patients with essential thrombocythemia. The ANAHYDRET‑ Study. Blood 2007; 110: 1038A.

8. Green A, Campbell P, Buck G et al. The Medical Research Council PT1 trial in essentials thrombocythemia. Blood 2004; 104: 5a– 6a.

9. Hoffman R, Prchal JT, Samuelson S et al. Philadelphia chromosome‑ negative myeloproliferative disorders: biology and treatment. Biol Blood Marrow Transplant 2007; 13 (Suppl 1): 64– 72.

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

11. Kaushansky K. The chronic myeloproliferative disorders and mutation of JAK2: Dameshek’s 54 year old speculation comes of age. Best Pract Res Clin Haematol 2007; 20: 5– 12.

12. Kralovics R, Passamonti F, Buser AS et al. A gain‑of‑ function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352: 1779– 1790.

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

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

15. 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: 46– 62.

16. 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: 239– 253.

17. 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: 133– 145.

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

19. 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: 29– 39.

20. Penka M, Schwarz J, Pytlík R et al. Doporučený postup diagnostiky a terapie esenciální trombocytémie a trombocytémie provázející myeloproliferativní onemocnění. Vnitř Lék 2005; 51: 741– 751.

21. 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: 775– 782.

22. 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: I– XII.

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

24. 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 essential thrombocythemia. Cancer Genet Cytogenet 2006; 167: 39– 42.

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

26. 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. Haematologica 2008; 1: 93.

27. StatSoft, Inc. Statistica (Data Analysis Software System) version 9.0. 2009. www.statsoft.com.

28. Silverstein MN, Tefferi A. Treatment of essential thrombocythemia with anagrelid. Semin Hematol 1999; 36 (1 Suppl 2): 23– 25.

29. 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: 2239– 2246.

30. 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: 413– 437.

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

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