Skip to main content

Treatment Algorithm for Primary and Secondary Myelofibrosis

  • Chapter
  • First Online:
Pathogenesis and Treatment of Leukemia
  • 468 Accesses

Abstract

The management of primary myelofibrosis (PMF), postpolycythemia vera myelofibrosis (PPV-MF), and postessential thrombocythemia (PET-MF) is driven by their clinicopathologic and genomic characteristics, and their risk categories. In this chapter, the treatment algorithms of PMF, PPV-MF, and PET-MF are discussed highlighting the relevance of the personalized approach.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mesa RA, Miller CB, Thyne M, et al. Differences in treatment goals and perception of symptom burden between patients with myeloproliferative neoplasms (MPNs) and hematologists/oncologists in the United States: findings from the MPN landmark survey. Cancer. 2017;123(3):449–58. https://doi.org/10.1002/cncr.30325.

    Article  PubMed  Google Scholar 

  2. Michiels JJ. Signs and symptoms of myeloproliferative neoplasms (MPN), quality of life, social activity, work participation and the impact of fatigue in Dutch MPN patients: a one country questionnaire investigation of 497 MPN patients. J Hematol Thrombo Dis. 2015;4(3):1000241. https://doi.org/10.4172/2329-8790.1000241.

    Article  Google Scholar 

  3. Finazzi G, Caruso V, Marchioli R, et al. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood. 2005;105(7):2664–70. https://doi.org/10.1182/blood-2004-09-3426.

    Article  PubMed  Google Scholar 

  4. Passamonti F, Rumi E, Arcaini L, et al. Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica. 2008;93(11):1645–51. https://doi.org/10.3324/haematol.13346.

    Article  PubMed  Google Scholar 

  5. Wolanskyj AP, Schwager SM, McClure RF, Larson DR, Tefferi A. Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc. 2006;81(2):159–66. https://doi.org/10.4065/81.2.159.

    Article  PubMed  Google Scholar 

  6. Vannucchi AM. How I treat polycythemia vera. Blood. 2014;124(22):3212–20. https://doi.org/10.1182/blood-2014-07-551929.

    Article  PubMed  Google Scholar 

  7. Rumi E, Cazzola M. How I treat essential thrombocythemia. Blood. 2016;128(20):2403–14. https://doi.org/10.1182/blood-2016-05-643346.

    Article  PubMed  Google Scholar 

  8. Björkholm M, Hultcrantz M, Derolf ÅR. Leukemic transformation in myeloproliferative neoplasms: therapy-related or unrelated? Best Pract Res Clin Haematol. 2014;27(2):141–53. https://doi.org/10.1016/j.beha.2014.07.003.

    Article  PubMed  Google Scholar 

  9. Sokolova MA, Turkina AG, Melikian AL, et al. Efficiency of interferon therapy in patients with essential thrombocythemia or polycythemia vera. Ter Arkh. 2016;88(12):69–77. https://doi.org/10.17116/terarkh2016881269-77.

    Article  PubMed  Google Scholar 

  10. Masarova L, Patel KP, Newberry KJ, et al. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. Lancet Haematol. 2017;4(4):e165–75. https://doi.org/10.1016/S2352-3026(17)30030-3.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gowin K, Thapaliya P, Samuelson J, et al. Experience with pegylated interferon alpha -2a in advanced myeloproliferative neoplasms in an international cohort of 118 patients. Haematologica. 2012;97(10):1570–3.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Quintás-Cardama A, Kantarjian H, Manshouri T, 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(32):5418–24. https://doi.org/10.1200/JCO.2009.23.6075.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kiladjian JJ, Massé A, Cassinat B, et al. Clonal analysis of erythroid progenitors suggests that pegylated interferon α-2a treatment targets JAK2 V617F clones without affecting TET2 mutant cells. Leukemia. 2010;24(8):1519–23. https://doi.org/10.1038/leu.2010.120.

    Article  PubMed  Google Scholar 

  14. Ianotto JC, Boyer-Perrard F, Gyan E, et al. Efficacy and safety of pegylated-interferon α-2a in myelofibrosis: a study by the FIM and GEM French cooperative groups. Br J Haematol. 2013;162(6):783–91. https://doi.org/10.1111/bjh.12459.

    Article  PubMed  Google Scholar 

  15. Silver RT, Vandris K, Goldman JJ. Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report. Blood. 2011;117(24):6669–72. https://doi.org/10.1182/blood-2010-11-320069.

    Article  PubMed  Google Scholar 

  16. Pizzi M, Silver RT, Barel A, Orazi A. Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response. Mod Pathol. 2015;28(10):1315–23. https://doi.org/10.1038/modpathol.2015.93.

    Article  PubMed  Google Scholar 

  17. Silver RT, Barel AC, Lascu E, et al. The effect of initial molecular profile on response to recombinant interferon-α (rIFNα) treatment in early myelofibrosis. Cancer. 2017;123(14):2680–7. https://doi.org/10.1002/cncr.30679.

    Article  PubMed  Google Scholar 

  18. Bewersdorf JP, Giri S, Wang R, et al. Interferon therapy in myelofibrosis: systematic review and meta-analysis. Clin Lymphoma Myeloma Leuk. 2020;20(10):e712–23. https://doi.org/10.1016/j.clml.2020.05.018.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Deininger M, Radich J, Burn TC, Huber R, Paranagama D, Verstovsek S. The effect of long-term ruxolitinib treatment on JAK2p.V617F allele burden in patients with myelofibrosis. Blood. 2015;126(13):1551–4. https://doi.org/10.1182/blood-2015-03-635235.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Verstovsek S, Passamonti F, Rambaldi A, et al. Ruxolitinib for essential thrombocythemia refractory to or intolerant of hydroxyurea: long-term phase 2 study results. Blood. 2017;130(15):1768–71. https://doi.org/10.1182/blood-2017-02-765032.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426–35. https://doi.org/10.1056/nejmoa1409002.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Verstovsek S, Mesa RA, Gotlib J, et al. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017;10(1):55. https://doi.org/10.1186/s13045-017-0417-z.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Harrison CN, Vannucchi AM, Kiladjian JJ, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016;30(8):1701–7. https://doi.org/10.1038/leu.2016.148.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 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(12):1117–2. https://doi.org/10.1056/nejmoa1002028.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Deisseroth A, Kaminskas E, Grillo J, et al. U.S. food and drug administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res. 2012;18(12):3212–7. https://doi.org/10.1158/1078-0432.CCR-12-0653.

    Article  PubMed  Google Scholar 

  26. Koren-Michowitz M, Landman J, Cohen Y, et al. JAK2V617F allele burden is associated with transformation to myelofibrosis. Leuk Lymphoma. 2012;53(11):2210–3. https://doi.org/10.3109/10428194.2012.682308.

    Article  PubMed  Google Scholar 

  27. Sørensen AL, Mikkelsen SU, Knudsen TA, et al. Ruxolitinib and interferon-α2 combination therapy for patients with polycythemia vera or myelofibrosis: a phase II study. Haematologica. 2020;105(9):2262–72. https://doi.org/10.3324/haematol.2019.235648.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mesa R, Miller CB, Thyne M, et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients’ overall health and productivity: the MPN landmark survey. BMC Cancer. 2016;16(1):167. https://doi.org/10.1186/s12885-016-2208-2.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Emanuel RM, Dueck AC, Geyer HL, et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol. 2012;30(33):4098–103. https://doi.org/10.1200/JCO.2012.42.3863.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Mesa RA, Niblack J, Wadleigh M, et al. The burden of fatigue and quality of life in myeloproliferative disorders (MPDs). Cancer. 2007;109(1):68–76. https://doi.org/10.1002/cncr.22365.

    Article  PubMed  Google Scholar 

  31. Abelsson J, Andréasson B, Samuelsson J, et al. Patients with polycythemia vera have worst impairment of quality of life among patients with newly diagnosed myeloproliferative neoplasms. Leuk Lymphoma. 2013;54(10):2226–30. https://doi.org/10.3109/10428194.2013.766732.

    Article  PubMed  Google Scholar 

  32. Gill H, Leung GMK, Yim R, et al. Myeloproliferative neoplasms treated with hydroxyurea, pegylated interferon alpha-2A or ruxolitinib: clinicohematologic responses, quality-of-life changes and safety in the real-world setting. Hematology (United Kingdom). 2020;25(1):247–57. https://doi.org/10.1080/16078454.2020.1780755.

    Article  Google Scholar 

  33. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787–98. https://doi.org/10.1056/nejmoa1110556.

    Article  PubMed  Google Scholar 

  34. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807. https://doi.org/10.1056/nejmoa1110557.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Passamonti F, Griesshammer M, Palandri F, et al. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017;18(1):88–99. https://doi.org/10.1016/S1470-2045(16)30558-7.

    Article  PubMed  Google Scholar 

  36. Samuelsson J, Hasselbalch H, Bruserud O, et al. A phase II trial of pegylated interferon alpha-2b therapy for polycythemia vera and essential thrombocythemia: feasibility, clinical and biologic effects, and impact on quality of life. Cancer. 2006;106(11):2397–405.

    Article  PubMed  Google Scholar 

  37. Blair HA. Fedratinib: first approval. Drugs. 2019;79(15):1719–25. https://doi.org/10.1007/s40265-019-01205-x.

    Article  PubMed  Google Scholar 

  38. Harrison CN, Schaap N, Vannucchi AM, et al. Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: an updated analysis of the JAKARTA2 study using stringent criteria for ruxolitinib failure. Am J Hematol. 2020;95(6):594–603. https://doi.org/10.1002/ajh.25777.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Mesa RA, Steensma DP, Pardanani A, et al. A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia. Blood. 2003;101(7):2534–41. https://doi.org/10.1182/blood-2002-09-2928.

    Article  PubMed  Google Scholar 

  40. Quintás-Cardama A, Kantarjian HM, Manshouri T, et al. Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis. J Clin Oncol. 2009;27(28):4760–6. https://doi.org/10.1200/JCO.2009.22.6548.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Tefferi A, Lasho TL, Mesa RA, Pardanani A, Ketterling RP, Hanson CA. Lenalidomide therapy in del(5)(q31)-associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions [5]. Leukemia. 2007;21(8):1827–8. https://doi.org/10.1038/sj.leu.2404711.

    Article  PubMed  Google Scholar 

  42. Begna KH, Pardanani A, Mesa R, et al. Long-term outcome of pomalidomide therapy in myelofibrosis. Am J Hematol. 2012;87(1):66–8. https://doi.org/10.1002/ajh.22233.

    Article  PubMed  Google Scholar 

  43. Hernández-Boluda JC, Alvarez-Larrán A, Gómez M, et al. Clinical evaluation of the European leukemiaNet criteria for clinicohaematological response and resistance/intolerance to hydroxycarbamide in essential thrombocythaemia. Br J Haematol. 2011;152(1):66–8. https://doi.org/10.1111/j.1365-2141.2010.08430.x.

    Article  Google Scholar 

  44. Alvarez-Larrán A, Pereira A, Cervantes F, 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(6):1363–9. https://doi.org/10.1182/blood-2011-10-387787.

    Article  PubMed  Google Scholar 

  45. Antonioli E, Guglielmelli P, Pieri L, et al. Hydroxyurea-related toxicity in 3,411 patients with Ph’-negative MPN. Am J Hematol. 2012;87(5):552–4. https://doi.org/10.1002/ajh.23160.

    Article  PubMed  Google Scholar 

  46. Gowin K, Jain T, Kosiorek H, et al. Pegylated interferon alpha – 2a is clinically effective and tolerable in myeloproliferative neoplasm patients treated off clinical trial. Leuk Res. 2017;54:73–7. https://doi.org/10.1016/j.leukres.2017.01.006.

    Article  PubMed  Google Scholar 

  47. WHO. WHO global tuberculosis report 2019. www.who.int/tb/publications/factsheet_global.pdf?ua=1. WHO. Published online 2020.

  48. Luo Z, Xie Y, Deng M, Zhou X, Ruan B. Prevalence of hepatitis B in the southeast of China: a population-based study with a large sample size. Eur J Gastroenterol Hepatol. 2011;23(8):695–700. https://doi.org/10.1097/MEG.0b013e328347322b.

    Article  PubMed  Google Scholar 

  49. Gowin K, Ballen K, Ahn KW, et al. Survival following allogeneic transplant in patients with myelofibrosis. Blood Adv. 2020;4(9):1966–73. https://doi.org/10.1182/bloodadvances.2019001084.

    Article  Google Scholar 

  50. Samuelson Bannow BT, Salit RB, Storer BE, et al. Hematopoietic cell transplantation for myelofibrosis: the dynamic international prognostic scoring system plus risk predicts post-transplant outcomes. Biol Blood Marrow Transplant. 2018;24(2):386–92. https://doi.org/10.1016/j.bbmt.2017.09.016.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Harinder Gill .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gill, H., Leung, G. (2023). Treatment Algorithm for Primary and Secondary Myelofibrosis. In: Gill, H., Kwong, YL. (eds) Pathogenesis and Treatment of Leukemia. Springer, Singapore. https://doi.org/10.1007/978-981-99-3810-0_40

Download citation

  • DOI: https://doi.org/10.1007/978-981-99-3810-0_40

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-99-3809-4

  • Online ISBN: 978-981-99-3810-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics