Annals of Hematology

, Volume 95, Issue 5, pp 719–732 | Cite as

Current opinion and consensus statement regarding the diagnosis, prognosis, and treatment of patients with essential thrombocythemia: a survey of the Spanish Group of Ph-negative Myeloproliferative Neoplasms (GEMFIN) using the Delphi method

  • C. BessesEmail author
  • J. C. Hernández-Boluda
  • M. Pérez Encinas
  • J. M. Raya
  • J. M. Hernández-Rivas
  • A. Jiménez Velasco
  • J. Martínez Lopez
  • V. Vicente
  • C. Burgaleta
  • on behalf of GEMFIN
Original Article


The current consensus on the diagnosis, prognosis, and treatment of essential thrombocythemia (ET) is based on experts’ recommendations. However, several aspects of the diagnosis of, prognosis of, and therapy for ET are still controversial. The Delphi method was employed with an expert panel of members of the Spanish Group of Ph-negative Myeloproliferative Neoplasms in order to identify the degree of agreement on the diagnosis, prognosis, and treatment of ET. Nine leading experts selected a total of 41 clinical hematologists with well-known expertise in ET. An electronic questionnaire was used to collect the questions rated in a four-step scale. The questions were grouped into four blocks: diagnosis, risk stratification, goals of therapy, and treatment strategy. After the first round consisting of 80 questions, a second round including 14 additional questions focused on the recommendations advocated by experts of the European LeukemiaNet in 2011 was analyzed. The median and mean values for the first and second rounds were calculated. A summary of the conclusions considered as the most representative of each block of questions is presented. The Delphi method is a powerful instrument to address the current approaches and controversies surrounding ET.


Essential thrombocythemia Delphi Consensus statement Survey questionnaire 



We are indebted to all members of GEMFIN who participated in this study.

This work was supported by grants PI13/00393, PI13/00557, and RD12/0036/0010 from the Instituto de Salud Carlos III; SGR 2014-567; and funding from Shire Pharmaceuticals Ibérica for the conduct of this study.

The authors are grateful to the physicians who kindly participated in the expert panel: Anna Angona, Hospital del Mar, Barcelona; Maria Luisa Antelo, Hospital de Navarra, Navarra; Elisa Arbelo, Hospital Virgen de Macarena, Sevilla; Ana Isabel Arribas, Hospital de la Axarquia, Málaga, and Inmaculada Ballesteros Hospital de la Axarquia, Málaga; Concepción Boqué, Hospital Universitario de Bellvitge, Barcelona; Gonzalo Caballero, Hospital Universitario Miguel Servet, Zaragoza; Dolores Fernandez, Hospital Clínico San Cecilio, Granada; Carlos Fernandez, Hospital Materno Infantil; Teresa Herrera, A Coruña; J. Valentín Garcia, Hospital Ramón y Cajal, Madrid; Montse Gómez, Hospital Quirón de Valencia, Valencia; Maria Teresa Gómez Casares, Hospital Dr. Negrín, Canarias; Jose Julio Hernandez, Hospital de San Eloy, Vizcaya; Juan Carlos Hernandez, Hospital Quirón Valencia, Valencia; Ana Jimenez, Hospital 12 de Octubre, Madrid; Ana Kerguelen, Hospital Universitario La Paz, Madrid; Elisa Luño, Hospital Universitario Central de Asturias, Asturias; Joaquín Martinez López, Hospital 12 de Octubre; María Isabel Mata, Hospital Costa del Sol, Málaga; Antonio Paz Coll, Hospital Puerto Real, Cádiz; Maria Jose Ramírez, Hospital de Jerez de la Frontera, Cádiz; Juan Nicolás Rodriguez, Hospital Juan Ramón Jimenez, Huelva; Adriana Simiele, Hospital Povisa, Pontevedra; Antonio Cervero, Hospital General Universitario de Valencia, Valencia; Jesús Maria Cesar, Hospital Ramón y Cajal, Madrid; Natalia de las Heras, Hospital Universitario de León; Margarita Fernandez de la Mata, Hospital Universitario Reina Sofía, Córdoba; Mar Hermosilla, Hospital San Pedro, Rioja; Esperanza Lavilla, Hospital Lucus Augusti, Lugo; Carmen Loureiro, Hospital do Meixoeiro, Pontevedra; Elena Magro, Hospital Príncipe de Asturias, Madrid; Sergio Ortegón, Hospital General de Llorena, Badajoz; Maria Antonia Peñalver, Hospital Universitario Severo Ochoa, Madrid; Maria Angeles Pérez, Hospital Fundación Jimenez Díaz, Madrid; and Maria del Carmen Santo, Hospital Central de Asturias, Asturias.

Authors’ contributions

Carlos Besses designed the study, collected the data, analyzed and interpreted the results, and wrote the paper; Juan Carlos Hernández-Boluda collected the data, analyzed and interpreted the results, and wrote the paper; Manuel Pérez Encinas collected the data, analyzed and interpreted the results, and approved the final version; José María Raya collected the data, analyzed and interpreted the results, and approved the final version; Jesús María Hernández-Rivas collected the data, analyzed and interpreted the results, and approved the final version; Antonio Jiménez Velasco collected the data, analyzed and interpreted the results, and approved the final version; Joaquín Martínez López collected the data, analyzed and interpreted the results, and approved the final version; Vicente Vicente collected the data, analyzed and interpreted the results, and approved the final version; and Carmen Burgaleta designed the study, collected the data, analyzed and interpreted the results, and approved the final version.

Compliance with ethical standards

Conflict of interest

Carlos Besses, Vicente Vicente, and Carmen Burgaleta received honoraria from Shire for speaking at symposia.

Supplementary material

277_2016_2614_MOESM1_ESM.doc (650 kb)
Table S1 (DOC 650 kb)
277_2016_2614_MOESM2_ESM.doc (86 kb)
Table S2 (DOC 86 kb)
277_2016_2614_MOESM3_ESM.doc (77 kb)
Table S3 (DOC 77 kb)
277_2016_2614_MOESM4_ESM.doc (114 kb)
Table S4 (DOC 113 kb)


  1. 1.
    Tefferi A, Vardiman JW (2008) Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 22(1):14–22CrossRefPubMedGoogle Scholar
  2. 2.
    Tefferi A, Thiele J, Vannucchi AM, Barbui T (2014) An overview on CALR and CSF3R mutations and a proposal for revision of WHO diagnostic criteria for myeloproliferative neoplasms. Leukemia 28(7):1407–1413CrossRefPubMedGoogle Scholar
  3. 3.
    Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, Hehlmann R, Hoffman R, Kiladjian JJ, Kröger N, Mesa R, McMullin MF, Pardanani A, Passamonti F, Vannucchi AM, Reiter A, Silver RT, Verstovsek S, Tefferi A; European LeukemiaNet (2011) Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European Leukemia Net. J Clin Oncol 29(6):761–770Google Scholar
  4. 4.
    Barosi G, Vannucchi AM, De Stefano V, Pane F, Passamonti F, Rambaldi F, Saglio A, Barbui T, Tura S (2014) Identifying and addressing unmet clinical needs in Ph-neg classical myeloproliferative neoplasms: a consensus-based SIE, SIES, GITMO position paper. Leuk Res 38(2):155–160CrossRefPubMedGoogle Scholar
  5. 5.
    Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant’Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schönegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R (2013) Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 369(25):2379–2390CrossRefPubMedGoogle Scholar
  6. 6.
    Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, Van Loo P, Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT, Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O’Meara S, McLaren S, Bianchi M, Silber Y, Dimitropoulou D, Bloxham D, Mudie L, Maddison M, Robinson B, Keohane C, Maclean C, Hill K, Orchard K, Tauro S, Du MQ, Greaves M, Bowen D, Huntly BJ, Harrison CN, Cross NC, Ron D, Vannucchi AM, Papaemmanuil E, Campbell PJ, Green AR (2013) Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 369(25):2391–2405CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, Milosevic JD, Them NC, Berg T, Elena C, Casetti IC, Milanesi C, Sant’Antonio E, Bellini M, Fugazza E, Renna MC, Boveri E, Astori C, Pascutto C, Kralovics R, Cazzola M (2014) JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 123(10):1544–1551CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L, Fanelli T, Bosi A, Vannucchi AM (2014) Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood 123(10):1552–1555CrossRefPubMedGoogle Scholar
  9. 9.
    Alvarez-Larran A, Cervantes F, Pereira A, Arellano-Rodrigo E, Perez-Andreu V, Hernandez-Boluda JC, Ayats R, Salvador C, Muntañola A, Bellosillo B, Vicente V, Hernandez-Nieto L, Burgaleta C, Xicoy B, Besses C (2010) Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood 116(8):1205–1210CrossRefPubMedGoogle Scholar
  10. 10.
    Alvarez-Larran A, Pereira A, Arellano-Rodrigo E, Hernandez-Boluda JC, Cervantes F, Besses C (2013) Cytoreduction plus low-dose aspirin versus cytoreduction alone as primary prophylaxis of thrombosis in patients with high-risk essential thrombocythaemia: an observational study. Br J Haematol 161(6):865–871CrossRefPubMedGoogle Scholar
  11. 11.
    Quintas-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL, Zhang SJ, Harris D, Estrov Z, Kantarjian H, Levine RL, Verstovsek S (2013) Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon alpha-2a. Blood 122(6):893–901CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE, ANAHYDRET Study Group (2013) Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET study, a randomized controlled trial. Blood 121(10):1720–1728CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Gisslinger H, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, Vannucchi AM, Tefferi A (2012) Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 120(26):5128–5133CrossRefPubMedGoogle Scholar
  14. 14.
    Passamonti F, Thiele J, Girodon F, Rumi E, Carobbio A, Gisslinger H, Kvasnicka HM, Ruggeri M, Randi ML, Gangat N, Vannucchi AM, Gianatti A, Gisslinger B, Müllauer L, Rodeghiero F, d’Amore ES, Bertozzi I, Hanson CA, Boveri E, Marino F, Maffioli M, Caramazza D, Antonioli E, Carrai V, Buxhofer-Ausch V, Pascutto C, Cazzola M, Barbui T, Tefferi A (2012) A prognostic model to predict survival in 867 World Health Organization-defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment. Blood 120(6):1197–1201CrossRefPubMedGoogle Scholar
  15. 15.
    Hsu C-C, Sandford BA (2007) The Delphi technique: making sense of consensus. Pract Assess Res Eval 12(10):1–8Google Scholar
  16. 16.
    Keeney S, Hasson F, McKenna H (2006) Consulting the oracle: ten lessons from using the Delphi technique in nursing research. J Adv Nurs 53(2):205–212CrossRefPubMedGoogle Scholar
  17. 17.
    Streiff MB, Smith B, Spivak JL (2002) The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members’ practice patterns. Blood 99(4):1144–1149CrossRefPubMedGoogle Scholar
  18. 18.
    Barbui T, Barosi G, Grossi A, Gugliotta L, Liberato LN, Marchetti M, Mazzuconi MG, Rodeghiero F, Tura S (2004) 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 89(2):215–232PubMedGoogle Scholar
  19. 19.
    Raya JM, Montes-Moreno S, Acevedo A, Ferrandez A, Fraga M, Garcia JF, Garcia M, Mayordomo-Aranda E, Menarquez J, Besses C, Calzada R, Rozman M (2014) Pathology reporting of bone marrow biopsy in myelofibrosis; application of the Delphi consensus process to the development of a standardized diagnostic report. J Clin Pathol 67(7):620–625CrossRefPubMedGoogle Scholar
  20. 20.
    Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, Rodeghiero F, d’Amore ES, Randi ML, Bertozzi I, Marino F, Vannucchi AM, Antonioli E, Carrai V, Gisslinger H, Buxhofer-Ausch V, Müllauer L, Carobbio A, Gianatti A, Gangat N, Hanson CA, Tefferi A (2011) Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol 29(23):3179–3184CrossRefPubMedGoogle Scholar
  21. 21.
    Alvarez-Larran A, Kerguelen A, Hernandez-Boluda JC, Perez-Encinas M, Ferrer-Marin F, Barez A, Martinez-Lopez J, Cuevas B, Mata MI, Garcia-Gutierrez V, Aragües P, Montesdeoca S, Burgaleta C, Caballero G, Hernandez-Rivas JA, Duran MA, Gomez-Casares MT, Besses C (2015) Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. Br J Haematol. doi: 10.1111/bjh.13886 Google Scholar
  22. 22.
    Barbui T, Thiele J, Vannucchi AM, Tefferi A (2014) Rethinking the diagnostic criteria of polycythemia vera. Leukemia 28(6):1191–1195CrossRefPubMedGoogle Scholar
  23. 23.
    Harrison CN, Bareford D, Butt N, Campbell P, Conneally E, Drummond M, Erber W, Everington T, Green AR, Hall GW, Hunt BJ, Ludlam CA, Murrin R, Nelson-Piercy C, Radia DH, Reilly JT, van der Walt J, Wilkins B, McMullin MF, British Committee for Standards in Haematology (2010) Guideline for investigation and management of adults and children presenting with a thrombocytosis. Br J Haematol 149(3):352–375CrossRefPubMedGoogle Scholar
  24. 24.
    Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, Kiladjian JJ, Lengfelder E, McMullin MF, Passamonti F, Reilly JT, Vannucchi AM, Barbui T (2009) Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood 113(20):4829–4833CrossRefPubMedGoogle Scholar
  25. 25.
    Barosi G, Mesa R, Finazzi G, Harrison C, Kiladjian JJ, Lengfelder E, McMullin MF, Passamonti F, Vannucchi AM, Besses C, Gisslinger H, Samuelsson J, Verstovsek S, Hoffman R, Pardanani A, Cervantes F, Tefferi A, Barbui T (2013) Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood 121(23):4778–4781CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Palandri F, Polverelli N, Catani L, Ottaviani E, Baccarani M, Vianelli N (2011) Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study. Ann Hematol 90(8):933–938CrossRefPubMedGoogle Scholar
  27. 27.
    Passamonti F, Rumi E, Pascutto C, Cazzola M, Lazzarino M (2009) Increase in leukocyte count over time predicts thrombosis in patients with low-risk essential thrombocythemia. J Thromb Haemost 7(9):1587–1589CrossRefPubMedGoogle Scholar
  28. 28.
    Campbell PJ, MacLean C, Beer PA, Buck G, Wheatley K, Kiladjian JJ, Forsyth C, Harrison CN, Green AR (2012) Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort. Blood 120(7):1409–1411CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Vannucchi AM, Antonioli E, Gisslinger H, Buxhofer-Ausch V, Finazzi G, Gangat N, Tefferi A, Barbui T (2011) Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood 117(22):5857–5859CrossRefPubMedGoogle Scholar
  30. 30.
    European Medicines Agency (2014) Xagrid summary of product characteristics (Internet). Shire Pharmaceuticals Ltd. (updated 2014). Available from: Accessed 27 July 2015
  31. 31.
    Kiladjian JJ, Mesa RA, Hoffman R (2011) The renaissance of interferon therapy for the treatment of myeloid malignancies. Blood 117(18):4706–4715CrossRefPubMedGoogle Scholar
  32. 32.
  33. 33.
    Alvarez-Larran A, Martinez-Aviles L, Hernandez-Boluda JC, Ferrer-Marin F, Antelo ML, Burgaleta C, Mata MI, Xicoy B, Martinez-Trillos A, Gomez-Casares MT, Duran MA, Marcote B, Ancochea A, Senin A, Angona A, Gomez M, Vicente V, Cervantes F, Bellosillo B, Besses C (2014) Busulfan in patients with polycythemia vera or essential thrombocythemia refractory or intolerant to hydroxyurea. Ann Hematol 93(12):2037–2043CrossRefPubMedGoogle Scholar
  34. 34.
    Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, Gangat N, Fjerza R, Belachew AA, Lasho TL, Ketterling RP, Hanson CA, Rambaldi A, Finazzi G, Thiele J, Barbui T, Pardanani A, Vannucchi AM (2014) Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood 124(16):2507–2513CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Cervantes F, Alvarez-Larran A, Talarn C, Gomez M, Montserrat E (2002) Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients. Br J Haematol 118(3):786–790CrossRefPubMedGoogle Scholar
  36. 36.
    Finazzi G, Ruggeri M, Rodeghiero F, Barbui T (2000) Second malignancies in patients with essential thrombocythaemia treated with busulphan and hydroxyurea: long-term follow-up of a randomized clinical trial. Br J Haematol 110(3):577–583CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • C. Besses
    • 1
    Email author
  • J. C. Hernández-Boluda
    • 2
  • M. Pérez Encinas
    • 3
  • J. M. Raya
    • 4
  • J. M. Hernández-Rivas
    • 5
  • A. Jiménez Velasco
    • 6
  • J. Martínez Lopez
    • 7
  • V. Vicente
    • 8
  • C. Burgaleta
    • 9
  • on behalf of GEMFIN
  1. 1.Hematology DepartmentHospital del MarBarcelonaSpain
  2. 2.Hematology DepartmentHospital ClínicoValenciaSpain
  3. 3.Hematology DepartmentHospital ClínicoSantiago de CompostelaSpain
  4. 4.Hematology DepartmentHospital Universitario de CanariasTenerifeSpain
  5. 5.Hematology DepartmentHospital Universitario de SalamancaSalamancaSpain
  6. 6.Hematology DepartmentHospital Regional UniversitarioMálagaSpain
  7. 7.Hematology DepartmentHospital 12 de OctubreMadridSpain
  8. 8.Hematology DepartmentHospital Morales MesseguerMurciaSpain
  9. 9.Hematology DepartmentHospital Príncipe de AsturiasAlcalá de HenaresSpain

Personalised recommendations