ABSTRACT
There has been a dearth of prospective randomized studies in essential (or primary) thrombocythemia (ET). To date, only two reports have been published. Cortelazzo et al reported the first study in 1995. The second is the Medical Research Council Primary Thrombocythemia 1 trial (MRC PT-1), the results and implications of which are the subject of this article.
KEYWORDS
Essential thrombocythemia - hydroxyurea - anagrelide - MRC PT-1
REFERENCES
-
1
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
-
2
Sterkers Y, Preudhomme C, Lai J L et al..
Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion.
Blood.
1998;
91
616-622
-
3
Murphy S.
Therapeutic dilemmas: balancing the risks of bleeding, thrombosis, and leukemic transformation in myeloproliferative disorders (MPD).
Thromb Haemost.
1997;
78
622-626
-
4
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
577-583
-
5
Silverstein M N, Petitt R M, Solberg Jr L A et al..
Anagrelide: a new drug for treating thrombocytosis.
N Engl J Med.
1988;
318
1292-1294
-
6
Fruchtman S M, Petitt R M, Gilbert H S, Fiddler S.
Anagrelide: analysis of long-term safety and leukemogenic potential in myeloproliferative disorders.
Leukemia Research.
2005;
29
481-491
-
7
Fruchtman S M, Petitt R M, Gilbert H S et al..
Anagrelide: Analysis of Long Term Safety and Leukemogenic Potential in Myeloproliferative Diseases (MPDs).
Blood.
2002;
100
xxx
, (abst)
-
8
Harrison C N, Campbell P J, Buck G et al..
Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.
N Engl J Med.
2005;
353
33-45
-
9
Harrison C N.
Platelets and thrombosis in myeloproliferativediseases.
Hematology (Am Soc Hematol Educ Program).
2005;
409-415
-
10
Jensen M K, de Nully B P, Lund B V, Nielsen O J, Hasselbalch H C.
Increased circulating platelet-leukocyte aggregates in myeloproliferative disorders is correlated to previous thrombosis, platelet activation and platelet count.
Eur J Haematol.
2001;
66
143-151
-
11
Falanga A, Marchetti M, Evangelista V et al..
Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera.
Blood.
2000;
96
4261-4266
-
12
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
523-530
-
13
Alvarez-Larran A, Garcia-Pagan J C, Abraldes J G et al..
Increased CD11b neutrophil expression in Budd-Chiari syndrome or portal vein thrombosis secondary to polycythaemia vera.
Br J Haematol.
2004;
124
329-335
-
14
Tang S S, Frojmovic M M.
Inhibition of platelet function by antithrombotic agents which selectively inhibit low-Km cyclic 3′,5′-adenosine monophosphate phosphodiesterase.
J Lab Clin Med.
1980;
95
241-257
-
15
Fleming J S, Buyniski J P.
A potent new inhibitor of platelet aggregation and experimental thrombosis, anagrelide (BL-4162A).
Thromb Res.
1979;
15
373-388
-
16
Balduini C L, Bertolino G, Noris P, Ascari E.
Effect of anagrelide on platelet count and function in patients with thrombocytosis and myeloproliferative disorders.
Haematologica.
1992;
77
40-43
-
17
Bellucci S, Legrand C, Boval B, Drouet L, Caen J.
Studies of platelet volume, chemistry and function in patients with essential thrombocythaemia treated with anagrelide.
Br J Haematol.
1999;
104
886-892
-
18
Storen E C, Tefferi A.
Long-term use of anagrelide in young patients with essential thrombocythemia.
Blood.
2001;
97
863-866
-
19
Petrides P E.
Anagrelide: a decade of clinical experience with its use for the treatment of primary thrombocythaemia.
Expert Opin Pharmacother.
2004;
5
1781-1798
-
20
Silverstein M N, Tefferi A.
Treatment of essential thrombocythemia with anagrelide.
Semin Hematol.
1999;
36
23-25
-
21
Thiele J, Kvasnicka H M, Fuchs N et al..
Anagrelide-induced bone marrow changes during therapy of chronic myeloproliferative disorders with thrombocytosis. an immunohistochemical and morphometric study of sequential trephine biopsies.
Haematologica.
2003;
88
1130-1138
-
22
Lev P R, Marta R F, Vassallu P, Molinas F C.
Variation of PDGF, TGFbeta, and bFGF levels in essential thrombocythemia patients treated with anagrelide.
Am J Hematol.
2002;
70
85-91
-
23
Lev P R, Salim J P, Kornblihtt L I et al..
PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide.
Am J Hematol.
2005;
78
155-157
-
24
Thiele J, Kvasnicka H M, Schmitt-Graeff A et al..
Effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukaemia: a comparative retrospective multicentre histological and clinical study.
Br J Haematol.
2000;
108
64-71
-
25
Lofvenberg E, Wahlin A, Roos G, Ost A.
Reversal of myelofibrosis by hydroxyurea.
Eur J Haematol.
1990;
44
33-38
-
26
Baxter E J, Scott L M, Campbell P J et al..
Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.
Lancet.
2005;
365
1054-1061
-
27
James C, Ugo V, Le Couedic J P et al..
A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.
Nature.
2005;
434
1144-1148
-
28
Kralovics R, Passamonti F, Buser A S et al..
A gain-of-function mutation of JAK2 in myeloproliferative disorders.
N Engl J Med.
2005;
352
1779-1790
-
29
Levine R L, Wadleigh M, Cools J et al..
Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.
Cancer Cell.
2005;
7
387-397
-
30
Zhao R, Xing S, Li Z et al..
Identification of an acquired JAK2 mutation in Polycythemia vera.
J Biol Chem.
2005;
280
22788-22792
-
31
Campbell P J, Scott L M, Buck G et al..
Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study.
Lancet.
2005;
366
1945-1953
-
32
Finazzi G, Ruggeri M, Rodeghiero F, Barbui T.
Efficacy and safety of long-term use of hydroxyurea in young patients with essential thrombocythemia and a high risk of thrombosis.
Blood.
2003;
101
3749
, (letter)
-
33
Harrison C N.
Essential thrombocythaemia: challenges and evidence-based management.
Br J Haematol.
2005;
130
153-165
-
34
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
-
35
Elliott M A, Teffer A.
Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia.
Br J Heamast.
2005;
128
275-290
Claire N HarrisonM.D.
Department of Haematology, Guys' and St Thomas' NHS Foundation Trust
Lambeth Palace Road, London SE1 7EH, United Kingdom
Email: Claire.Harrison@gstt.nhs.uk