Revista de Hematología

Contents by Year, Volume and Issue

Table of Contents

General Information

Instructions for Authors

Message to Editor

Editorial Board

>Journals >Revista de Hematología >Year 2016, Issue 2

Palmer J, Mesa R
Treatment approaches to polycythemia vera and myelofibrosis
Rev Hematol Mex 2016; 17 (2)

Language: Inglés
References: 60
Page: 129-138
PDF: 447.27 Kb.

Full text


Myeloproliferative neoplasms consist of a diverse group of disorders. Over the last 10 years, with better understanding of pathophysiology of these disorders, there are many more treatment options available to patients with these diseases. Further, improved understanding of the underlying genetic landscape has led to improved prognostication which helps identify appropriate therapeutic options. For polycythemia vera, initial therapy generally includes aspirin and phlebotomy. However, in patients who do not achieve an appropriate response to phlebotomy, hydroxyurea or ruxolitinib can be considered. In patients who have myelofibrosis, therapy is determined by symptom burden. In patients who have significant constitutional symptoms, a JAK inhibitor, such as ruxolitinib is an appropriate choice. There are many novel therapies under investigation for patients with myelofibrosis, including anti-fibrotic agents, novel JAK inhibitors, telomerase inhibitors and allogeneic stem cell transplant.

Key words: polycythemia vera, myelofibrosis, treatment.


  1. Levine RL, Wadleigh M, Cools J, Ebert BL, 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.

  2. James C, Ugo V, Le Couedic JP, Staerk J, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005;434:1144-1148.

  3. Kralovics R, Passamonti F, Buser AS, Teo S-S, et al. A gain-offunction mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005;352:1779-1790.

  4. Baxter EJ, Scott LM, Campbell PJ, East C, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054-1061.

  5. Vainchenker W, Constantinescu SN. JAK/STAT signaling in hematological malignancies. Oncogene 2013;32:2601- 2613.

  6. Pikman Y, Lee BH, Mercher T, McDowell E, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Medicine 2006;3:270.

  7. Pardanani AD, Levine RL, Lasho T, Pikman Y, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006;108:3472- 3476.

  8. Scott LM, Tong W, Levine RL, Scott MA, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007;356:459-468.

  9. Pardanani A, Lasho TL, Finke C, Hanson CA, Tefferi A. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia 2007;21:1960-1963.

  10. Nangalia J, Massie CE, Baxter EJ, Nice FL, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013;369:2391-2405.

  11. Kim SY, Im K, Park SN, Kwon J, et al. CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable. Am J Clin Pathol 2015;143:635-644.

  12. Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, et al. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Blood 2013;122:893-901.

  13. Vannucchi AM, Lasho TL, Guglielmelli P, Biamonte F, et al. Mutations and prognosis in primary myelofibrosis. Leukemia 2013;27:1861-1869.

  14. Tefferi A, Rumi E, Finazzi G, Gisslinger H, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 2013;27:1874-1881.

  15. Geyer HL, Mesa RA. Therapy for myeloproliferative neoplasms: when, which agent, and how? ASH Education Program Book 2014;2014:277-286.

  16. Barbui T, Barosi G, Birgegard G, Cervantes F, et al. Philadelphia- negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol 2011;29:761-770.

  17. Marchioli R, Finazzi G, Specchia G, Cacciola R, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 2013;368:22-33.

  18. Landolfi R, Marchioli R, Kutti J, Gisslinger H, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Eng J Med 2004;350:114-124.

  19. Álvarez-Larrán A, Pereira A, Cervantes F, Arellano-Rodrigo E, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood 2012;119:1363-1369.

  20. Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, et al. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 2009;27:5418-5424.

  21. Kiladjian J-J, Cassinat B, Chevret S, Turlure P, et al. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 2008;112:3065-3072.

  22. Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med 2015;372:426-435.

  23. Passamonti F, Cervantes F, Vannucchi AM, Morra E, et al. Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis. Blood 2010;116:2857-2858.

  24. Gangat N, Caramazza D, Vaidya R, George G, et al. DIPSS Plus: A refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 2011;29:392-397.

  25. Rumi E, Pietra D, Pascutto C, Guglielmelli P, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood 2014;124:1062-1069.

  26. Tefferi A, Guglielmelli P, Larson DR, Finke C, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood 2014;124:2507-2513.

  27. Guglielmelli P, Lasho TL, Rotunno G, Score J, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia 2014;28:1804-1810.

  28. Kroeger N, Panagiota V, Zabelina T, Araujo Cruz MM, et al. Impact of molecular genetics on disease-free survival in myelofibrosis patients following allogeneic stem cell transplantation. Blood 2015;126:352.

  29. Verstovsek S, Mesa RA, Gotlib J, Levy RS, et al. A doubleblind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366:799-807.

  30. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, et al. JAK Inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366:787-798.

  31. Verstovsek S, Kantarjian HM, Estrov Z, Cortes JE, et al. Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood 2012;120:1202-1209.

  32. Passamonti F, Maffioli M, Cervantes F, Vannucchi AM, et al. Impact of ruxolitinib on the natural history of primary myelofibrosis: a comparison of the DIPSS and the COMFORT-2 cohorts. Blood 2014;123:1833-1835.

  33. Harrison CN, Vannucchi AM, Kiladjian JJ, Al-Ali HK, et al. Long-term efficacy and safety in comfort-II, a phase 3 study comparing ruxolitinib with best available therapy for the treatment of myelofibrosis: 5-year final study results. Blood 2015;126:59.

  34. Mesa R, Egyed M, Szoke A, Suvorov A, et al. Results of PERSIST-1 phase III study of pacritinib (PAC) vs best available therapy (BAT) in primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) or post essential thrombocythemia- myelofibrosis (PET-MF). ASCO2015;33.

  35. Gotlib J, Gupta V, Roberts AW, Wadleigh M, et al. Update on the long-term efficacy and safety of momelotinib, a JAK1 and JAK2 inhibitor, for the treatment of myelofibrosis. Blood 2013;122:108.

  36. Abdelrahman RA, Begna KH, Al-Kali A, Hogan WJ, et al. Momelotinib treatment-emergent neuropathy: prevalence, risk factors and outcome in 100 patients with myelofibrosis. Br J Haematol 2015;169:77-80.

  37. Gowin KL, Kosiorek HE, Dueck AC, Mascarenhas J, et al. Final analysis of a multicenter pilot phase 2 study of ruxolitinib and danazol in patients with myelofibrosis. Blood 2015;126:1618.

  38. Stegelmann F, Bangerter M, Heidel FH, Griesshammer M, et al. A Phase-Ib/II study of ruxolitinib plus pomalidomide in myelofibrosis. Blood 2015;126:826.

  39. Gupta V, Harrison CN, Hasselbalch H, Pieri L, et al. Phase 1b/2 study of the efficacy and safety of sonidegib (LDE225) in combination with ruxolitinib (INC424) in patients with myelofibrosis. Blood 2015;126:825.

  40. Mikkelsen SU, Kjær L, Skov V, Bjørn ME, et al. Safety and efficacy of combination therapy of interferonalpha2+ JAK1-2 inhibitor in the philadelphia-negative chronic myeloproliferative neoplasms. Preliminary results from the danish combi-trial-an open label, single arm, nonrandomized multicenter. Blood 2015;126:824.

  41. Gilbert HS. Long term treatment of myeloproliferative disease with interferon-a-2b. Cancer 1998;83:1205-1213.

  42. Tefferi A, Lasho TL, Begna KH, Patnaik MM, et al. A Pilot study of the telomerase inhibitor imetelstat for myelofibrosis. N Engl J Med 2015;373:908-919.

  43. Verstovsek S, Mesa RA, Foltz LM, Gupta V, et al. PRM-151 in myelofibrosis: durable efficacy and safety at 72 weeks. Blood 2015;126:56.

  44. Mascarenhas J, Li T, Sandy L, Newsom C, et al. Antitransforming growth factor-b therapy in patients with myelofibrosis. Leuk Lymphoma 2013;55:450-452.

  45. Stewart WA, Pearce R, Kirkland KE, Bloor A, et al. The role of allogeneic SCT in primary myelofibrosis: a British Society for Blood and Marrow Transplantation study. Bone Marrow Transplant 2010;45:1587-1593.

  46. Patriarca F, Bacigalupo A, Sperotto A, Isola M, et al. Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica 2008;93:1514-1522.

  47. Kerbauy DMB, Gooley TA, Sale GE, Flowers MED, et al. Hematopoietic Cell Transplantation as curative therapy for idiopathic myelofibrosis, advanced polycythemia vera, and essential thrombocythemia. Biol Blood Marrow Transplant 2007;13:355-365.

  48. Rondelli D, Barosi G, Bacigalupo A, Prchal JT, et al. Allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning in intermediate- or high-risk patients with myelofibrosis with myeloid metaplasia. Blood 2005;10:4115-4119.

  49. Deeg HJ, Bredeson C, Farnia S, Ballen K, et al. Hematopoietic cell transplantation as curative therapy for patients with myelofibrosis: long-term success in all age groups. Biol Blood Marrow Transplant 2015;21:1883-1887.

  50. Samuelson S, Sandmaier BM, Heslop HE, Popat U, et al. Allogeneic haematopoietic cell transplantation for myelofibrosis in 30 patients 60-78 years of age. Bri J Haematol 2011;153:76-82.

  51. Gupta V, Gotlib J, Radich JP, Kröger NM, et al. Janus kinase inhibitors and allogeneic stem cell transplantation for myelofibrosis. Biol Blood Marrow Transplant 2014;20:1274-1281.

  52. Rondelli D, Goldberg JD, Isola L, Price LS, et al. MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. Blood 2014;124:1183-1191.

  53. Gupta V, Malone AK, Hari PN, Ahn KW, et al. reducedintensity hematopoietic cell transplantation for patients with primary myelofibrosis: a cohort analysis from the center for international blood and marrow transplant research. Biol Blood Marrow Transplant 2014;20:89-97.

  54. Alchalby H, Zabelina T, Stübig T, van Biezen A, et al. Allogeneic stem cell transplantation for myelofibrosis with leukemic transformation: a study from the myeloproliferative neoplasm subcommittee of the CMWP of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2014;20:279-281.

  55. Abelsson J, Merup M, Birgegard G, WeisBjerrum O, et al. The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries. Bone Marrow Transplant 2012;47:380-386.

  56. Robin M, Tabrizi R, Mohty M, Furst S, et al. Allogeneic haematopoietic stem cell transplantation for myelofibrosis: a report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). Br J Haematol 2011;152:331-339.

  57. Ballen KK, Shrestha S, Sobocinski KA, Zhang MJ, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant 2010;16:358-367.

  58. Kröger N, Holler E, Kobbe G, Bornhäuser M, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood 2009;114:5264-5270.

  59. Kröger N, Giorgino T, Scott BL, Ditschkowski M, et al. Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis. Blood 2015;125:3347-3350.

  60. Tefferi A, Guglielmelli P, Lasho TL, Rotunno G, et al. CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients. Leukemia 2014;28:1494-1500.

>Journals >Revista de Hematología >Year 2016, Issue 2

· Journal Index 
· Links 

Copyright 2019