Current Hematologic Malignancy Reports

, Volume 6, Issue 1, pp 28–35 | Cite as

Special Issues in Myeloproliferative Neoplasms



Special issues in myeloproliferative neoplasms (MPN) comprise clinical conditions with high relevance for the duration and quality of the patient’s life, but with limited evidence to support sound diagnostic and therapeutic recommendations and a low probability of being solved by the current standard of clinical research. These issues include MPN in pregnancy and in children, abdominal vein thrombosis, bleeding complications, surgery, pruritus, and leukemic transformation. Practical suggestions to guide clinical decisions in these settings remain largely empirical, but recently developed guidelines based on experts’ consensus may help to tackle these problems. This article reviews the state of the art regarding these issues, with special emphasis on experts’ consensus recommendations.


Chronic myeloproliferative neoplasms MPN Polycythemia vera Essential thrombocythemia Primary myelofibrosis Pregnancy Pediatric patients Children Splanchnic vein thrombosis Bleeding Surgery Pruritus Leukemic transformation Hydroxyurea 



Conflicts of Interest: T. Barbui: Honoraria, speaking fees, and travel expenses from Shire; G. Finazzi: none.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    • Barbui T, Barosi G, Birgegard G, et al.: Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol 2011 (in press). These are the most up-to-date management recommendations for Philadelphia-negative classic myeloproliferative neoplasms, based on the results of a systematic consensus process by a panel of 21 experts appointed by the European LeukemiaNet. Google Scholar
  2. 2.
    Harrison C. Pregnancy and its management in the Philadelphia negative myeloproliferative diseases. Br J Haematol 2005; 129:293–306.CrossRefPubMedGoogle Scholar
  3. 3.
    Griesshammer M, Struve S, Harrison CM. Essential Thrombocythemia/Polycythemia Vera and pregnancy: the need for an observational study in Europe. Semin Thromb Haemost 2006; 32:422–429.CrossRefGoogle Scholar
  4. 4.
    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; 89:215–32.PubMedGoogle Scholar
  5. 5.
    Elliott MA, Tefferi A. Thrombocythaemia and pregnancy. Best Pract Res Clin Hematol 2003; 16:227–242.CrossRefGoogle Scholar
  6. 6.
    Gangat N, Wolanskyj AP, Schwager S, Tefferi A. Predictors of pregnancy outcome in essential thrombocythemia: a single institution study of 63 pregnancies. Eur J Haematol 2009; 82:350–353.CrossRefPubMedGoogle Scholar
  7. 7.
    Passamonti F, Randi ML, Rumi E, et al.: Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation. Blood 2007; 110:485–489.CrossRefPubMedGoogle Scholar
  8. 8.
    Robinson S, Bewley S, Hunt BJ, Radia DH, Harrison CN. The management and outcome of 18 pregnancies in women with polycythemia vera. Haematologica 2005; 90:1477–83.PubMedGoogle Scholar
  9. 9.
    • Harrison CN, Bareford D, Butt N, et al.: Guideline for investigation and management of adults and children presenting with a thrombocytosis. Br J Haematol 2010; 149:352-375. This recent and comprehensive guideline produced by the British Committee for Standards in Haematology provides health care professionals with clear guidance on the investigation and management of thrombocytosis in both adult and pediatric patients. CrossRefPubMedGoogle Scholar
  10. 10.
    Tefferi A, Passamonti F. Essential thrombocythemia and pregnancy: observations from recent studies and management recommendations. Am J Hematol 2009; 84:629–630.CrossRefPubMedGoogle Scholar
  11. 11.
    Dame C, Sutor AH. Primary and secondary thrombocytosis in childhood. Br J Haematol 2005; 129:165–177.CrossRefPubMedGoogle Scholar
  12. 12.
    Belay ED, Bresee JS, Holman RC, et al.: Reye’s syndrome in the United States from 1981 through 1997. N Engl J Med 1999; 340:1377–1382.CrossRefPubMedGoogle Scholar
  13. 13.
    Chung RT, Iafrate AJ, Amrein PC, et al.: Case 15-2006: a 46-year-old woman with sudden onset of abdominal distention. N Engl J Med 2006; 354:2166–75.CrossRefPubMedGoogle Scholar
  14. 14.
    Chait Y, Condat B, Cazals-Hatem D, et al.: Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis. Br J Haematol 2005; 129:553–560.CrossRefPubMedGoogle Scholar
  15. 15.
    Patel RK, Lea N, Heneghan A, et al.: Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology 2006; 130:2031–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Kiladjian JJ, Cervantes F, Leebek FWG, 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 :4922–4929.CrossRefPubMedGoogle Scholar
  17. 17.
    Martinelli I, Franchini M, Mannucci PM. How I treat rare venous thrombosis. Blood 2008; 112:4818–4823.CrossRefPubMedGoogle Scholar
  18. 18.
    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.CrossRefPubMedGoogle Scholar
  19. 19.
    Narayanan Menon KV, Shah V, Kamath PS. The Budd-Chiari syndrome. N Engl J Med 2004; 350:578–585.CrossRefGoogle Scholar
  20. 20.
    Landolfi R, Marchioli R, Kutti J, et al.: Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004; 350:114–124.CrossRefPubMedGoogle Scholar
  21. 21.
    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; 23:2224–32.CrossRefPubMedGoogle Scholar
  22. 22.
    Harrison CN, Campbell PJ, Buck G, et al.: Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 2005; 353:33–45.CrossRefPubMedGoogle Scholar
  23. 23.
    Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2005; 128:275–90.CrossRefPubMedGoogle Scholar
  24. 24.
    Landolfi R, Cipriani MC, Novarese L. Thrombosis and bleeding in polycythemia vera and essential thrombocythemia: pathogenetic mechanisms and prevention. Best Pract Res Clinical Haematol 2006; 19:617–33.CrossRefGoogle Scholar
  25. 25.
    Schafer AI. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood 2006; 107:4214–22.CrossRefPubMedGoogle Scholar
  26. 26.
    Wagstaff AJ, Keating GM. Anagrelide. A review of its use in the management of essential thrombocythemia. Drugs 2006; 66:111-31.CrossRefPubMedGoogle Scholar
  27. 27.
    Cervera JS, Mena-Duran AV, Piqueras CS. The use of recombinant factor VIIa in a patient with essential thrombocythemia with uncontrolled surgical bleeding. Thromb Haemost 2005, 93:383–384.PubMedGoogle Scholar
  28. 28.
    Ruggeri M, Rodeghiero F, Tosetto A, et al.: Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood 2008; 111:666–671.CrossRefPubMedGoogle Scholar
  29. 29.
    Mesa RA. How I treat symptomatic splenomegaly in patients with myelofibrosis. Blood 2009; 113:5394–5400.CrossRefPubMedGoogle Scholar
  30. 30.
    Randi ML, Fabris F, Ruzzon E, et al.: Splenectomy after portal thrombosis in patients with polycythemia vera and essential thrombocythemia. Haematologica 2002; 87:1180–4.PubMedGoogle Scholar
  31. 31.
    Tefferi A, Mesa RA, Nagorney DM, et al.: Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood 2000; 95:226–33.Google Scholar
  32. 32.
    Saini KS, Patnaik MM, Tefferi A. Polycythemia Vera-associated pruritus and its management. Eur J Clin Invest 2010; 40:828–834.CrossRefPubMedGoogle Scholar
  33. 33.
    Pieri L, Bogani C, Guglielmelli P, et al.: The JAK2V617F mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera. Haematologica 2009; 94:1484–1488.CrossRefGoogle Scholar
  34. 34.
    • Verstovsek S, Kantarjian H, Mesa RA, et al.: Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010; 363:1117-1127. The first phase I/II clinical trial of a selective JAK2 inhibitor published in full, showing marked and durable clinical benefits in patients with myelofibrosis. CrossRefPubMedGoogle Scholar
  35. 35.
    Vannucchi AM, Guglielmelli P, Gattoni E, et al.: RAD001, an inhibitor of mTOR, shows clinical activity in a phase I/II study in patients with primary myelofibrosis (PMF) and post polycythemia vera/essential thrombocythemia myelofibrosis (PPV/PET MF). [abstract 307]. Presented at the 51th American Society of Hematology Congress, New Orleans, Louisiana, December 5–8, 2009.Google Scholar
  36. 36.
    Rambaldi A, Dellacasa CM, Finazzi G, et al.: A pilot study of the hystone-deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms. Br J Haematol 2010; 150:446–455.PubMedGoogle Scholar
  37. 37.
    Landaw SA. Acute leukemia in polycythemia vera. In Polycythyemia Vera and the Myeloproliferative Disorders. Edited by Wasserman LR, Berk PD, Berlin NI. Philadelhia: WP Saunders Co. 1995:154-165.Google Scholar
  38. 38.
    Barbui T. The leukemia controversy in myeloproliferative disorders: Is it a natural progression of disease, a secondary sequela of therapy, or a combination of both? Semin Hematol 2004; 41 (Suppl 3):15–17.CrossRefPubMedGoogle Scholar
  39. 39.
    Cortelazzo S, Finazzi G, Ruggeri M, et al.: Hydroxyurea in the treatment of patients with essential thrombocythemia at high risk of thrombosis: a prospective randomized trial. N Engl J Med 1995; 332:1132–1136CrossRefPubMedGoogle Scholar
  40. 40.
    Finazzi G, Barbui T. How I treat patients with polycythemia vera. Blood 2007; 109:5104–11.CrossRefPubMedGoogle Scholar
  41. 41.
    Gangat N, Wolanskyi AP, McClure, et al.: Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia 2007; 21:270-276.CrossRefPubMedGoogle Scholar
  42. 42.
    Finazzi G, Caruso V, Marchioli R, et al.: Acute leukemia in polycythemia vera. An analysis of 1,638 patients enrolled in a prospective observational study. Blood 2005; 105:2664–2670.CrossRefPubMedGoogle Scholar
  43. 43.
    Bjorkholm M, Derolf AR, Ekstrand C, et al.: Clinical risk for AML/MDS transformation in Philadelphia negative chronic myeloproliferative neoplasms. A population-based nested case-control study in Sweden [abstract 1085]. Presented at the 14th European Hematology Association Congress, Berlin, June 4–7, 2009.Google Scholar
  44. 44.
    Lanzkron S, Strouse JJ, Wilson R, et al.: Systematic review: hydroxyurea for the treatment of adults with sickle cell disease. Ann Intern Med 2008; 148:939–955.PubMedGoogle Scholar
  45. 45.
    Kiladjian JJ, Chevret S, Dosquet C, et al.: Long-term outcome in polycythemia vera: final analysis of a randomized trial comparing hydroxyurea (HU) to Pipobroman (Pi). [abstract 1746]. Presented at the 50th American Society of Hematology Congress, San Francisco, California, December 6–9, 2008.Google Scholar
  46. 46.
    Sterkers Y, Preudhomme C, Lai JL, et al.: Acute myeloid leukemia and myelodisplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion. Blood 1998; 91:616–622.PubMedGoogle Scholar
  47. 47.
    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; 110:1092–1097.CrossRefPubMedGoogle Scholar
  48. 48.
    Campbell PJ, Baxter EJ, Beer PA, et al.: Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation. Blood 2006; 108:3548–3555.CrossRefPubMedGoogle Scholar
  49. 49.
    Mesa RA, Li CY, Ketterling RP, et al.: Leukemic transformation in myelofibrosis with myeloid metaplasia: a single institution experience with 91 cases. Blood 2005; 105:973–977.CrossRefPubMedGoogle Scholar
  50. 50.
    Tam CS, Nussenzveig Rm, Popat U, et al.: The natural history and treatment outcome of blast phase BCR-ABL- myeloproliferative neoplasms. Blood 2008; 112:1628-1637.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Research FoundationOspedali RiunitiBergamoItaly
  2. 2.Division of HematologyOspedali RiunitiBergamoItaly

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