Myelofibrosis - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Myelofibrosis is a reactive and reversible process common to many malignant and benign bone marrow disorders. It can present de novo as primary myelofibrosis (PMF), or as secondary (reactive) myelofibrosis if caused by another disorder, drug treatment, or toxic agent.
PMF (the focus of this topic) is a chronic progressive myeloproliferative neoplasm (MPN). Median survival is approximately 6 years, which is much shorter than that for other MPNs (e.g., polycythemia vera, essential thrombocythemia). However, survival outcomes vary, ranging from <1 year to >30 years.
Bone marrow fibrosis, extramedullary hematopoiesis, leukoerythroblastosis, and splenomegaly are hallmarks of PMF.
Observation is appropriate for patients with asymptomatic, low-risk disease without hyperuricemia or a remedial cause for anemia.
Treatment with Janus kinase inhibitors and hematopoietic stem cell transplant (along with supportive care) should be considered for patients with symptomatic and/or high-risk disease. Allogeneic hematopoietic stem cell transplant is the only treatment with curative potential.

Peripheral blood smear showing leukoerythroblastic reaction: teardrop red blood cells (black arrows), myelocyte (red arrow), and promyelocyte (blue arrow)

From the collection of A. Emadi and J.L. Spivak; used with permission

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Definition

Epidemiology

Etiology

Pathophysiology

Images

Peripheral blood smear showing teardrop red blood cells (black arrows), 2 nucleated red blood cells (red arrows), and a myelocyte (blue arrow)
Peripheral blood smear showing leukoerythroblastic reaction: teardrop red blood cells (black arrows), myelocyte (red arrow), and promyelocyte (blue arrow)
Bone marrow biopsy showing increased reticulin deposition
Trephine bone marrow biopsy showing megakaryocytic hyperplasia and clustering

Citations

Key Articles

Tefferi A. Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023 May;98(5):801-21.[Abstract][Full Text]
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: myeloproliferative neoplasms [internet publication].[Full Text]
McLornan DP, Godfrey AL, Green A, et al. Diagnosis and evaluation of prognosis of myelofibrosis: a British Society for Haematology guideline. Br J Haematol. 2024 Jan;204(1):127-35.[Abstract][Full Text]
Kröger N, Bacigalupo A, Barbui T, et al. Indication and management of allogeneic haematopoietic stem-cell transplantation in myelofibrosis: updated recommendations by the EBMT/ELN International Working Group. Lancet Haematol. 2024 Jan;11(1):e62-74.[Abstract]
McLornan DP, Psaila B, Ewing J, et al. The management of myelofibrosis: a British Society for Haematology guideline. Br J Haematol. 2024 Jan;204(1):136-50.[Abstract][Full Text]

Referenced Articles

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24. Tefferi A. Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023 May;98(5):801-21.[Abstract][Full Text]
25. Milosevic Feenstra JD, Nivarthi H, Gisslinger H, et al. Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms. Blood. 2016 Jan 21;127(3):325-32.[Abstract][Full Text]
26. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: myeloproliferative neoplasms [internet publication].[Full Text]
27. Rumi E, Trotti C, Vanni D, et al. The genetic basis of primary myelofibrosis and its clinical relevance. Int J Mol Sci. 2020 Nov 24;21(23):8885.[Abstract][Full Text]
28. Tefferi A. Pathogenesis of myelofibrosis with myeloid metaplasia. J Clin Oncol. 2005 Nov 20;23(33):8520-30.[Abstract]
29. Agarwal A, Morrone K, Bartenstein M, et al. Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-beta. Stem Cell Investig. 2016 Feb 26;3:5.[Abstract][Full Text]
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34. Passamonti F, Giorgino T, Mora B, et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017 Dec;31(12):2726-31.[Abstract]
35. Cervantes F, Pereira A, Esteve J, et al. Identification of 'short-lived' and 'long-lived' patients at presentation of idiopathic myelofibrosis. Br J Haematol. 1997 Jun;97(3):635-40.[Abstract]
36. Glew RH, Haese WH, Mclntyre PA. Myeloid metaplasia with myelofibrosis: the clinical spectrum of extramedullary hematopoiesis and tumor formation. Johns Hopkins Med J. 1973 May;132(5):253-70.[Abstract]
37. Mughal TI, Vaddi K, Sarlis NJ, et al. Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes. Int J Gen Med. 2014 Jan 29;7:89-101.[Abstract][Full Text]
38. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405.[Abstract][Full Text]
39. McLornan DP, Godfrey AL, Green A, et al. Diagnosis and evaluation of prognosis of myelofibrosis: a British Society for Haematology guideline. Br J Haematol. 2024 Jan;204(1):127-35.[Abstract][Full Text]
40. Andriani A, Latagliata R, Anaclerico B, et al. Spleen enlargement is a risk factor for thrombosis in essential thrombocythemia: Evaluation on 1,297 patients. Am J Hematol. 2016 Mar;91(3):318-21.[Abstract][Full Text]
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45. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009 Mar 26;113(13):2895-901.[Abstract][Full Text]
46. Gangat N, Caramazza D, Vaidya R, 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 Feb 1;29(4):392-7.[Abstract][Full Text]
47. Guglielmelli P, Lasho TL, Rotunno G, et al. MIPSS70: mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis. J Clin Oncol. 2018 Feb 1;36(4):310-8.[Abstract][Full Text]
48. Tefferi A, Guglielmelli P, Nicolosi M, et al. GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis. Leukemia. 2018 Jul;32(7):1631-42.[Abstract][Full Text]
49. Gagelmann N, Ditschkowski M, Bogdanov R, et al. Comprehensive clinical-molecular transplant scoring system for myelofibrosis undergoing stem cell transplantation. Blood. 2019 May 16;133(20):2233-42.[Abstract][Full Text]
50. Kröger N, Bacigalupo A, Barbui T, et al. Indication and management of allogeneic haematopoietic stem-cell transplantation in myelofibrosis: updated recommendations by the EBMT/ELN International Working Group. Lancet Haematol. 2024 Jan;11(1):e62-74.[Abstract]
51. Hernández-Boluda JC, Pereira A, Correa JG, et al. Performance of the myelofibrosis secondary to PV and ET-prognostic model (MYSEC-PM) in a series of 262 patients from the Spanish registry of myelofibrosis. Leukemia. 2018 Feb;32(2):553-5.[Abstract][Full Text]
52. McLornan DP, Psaila B, Ewing J, et al. The management of myelofibrosis: a British Society for Haematology guideline. Br J Haematol. 2024 Jan;204(1):136-50.[Abstract][Full Text]
53. Silver RT, Kiladjian JJ, Hasselbalch HC. Interferon and the treatment of polycythemia vera, essential thrombocythemia and myelofibrosis. Expert Rev Hematol. 2013 Feb;6(1):49-58.[Abstract]
54. Mesa RA, Vannucchi AM, Mead A, et al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017 May;4(5):e225-36.[Abstract][Full Text]
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56. Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in Janus kinase inhibitor-naïve patients with myelofibrosis. J Clin Oncol. 2017 Dec 1;35(34):3844-50.[Abstract][Full Text]
57. Harrison CN, Vannucchi AM, Platzbecker U, et al. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018 Feb;5(2):e73-81.[Abstract][Full Text]
58. Mesa R, Harrison C, Oh ST, et al. Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis. Leukemia. 2022 Sep;36(9):2261-8.[Abstract][Full Text]
59. Harrison CN, Schaap N, Vannucchi AM, et al. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol. 2017 Jul;4(7):e317-24.[Abstract]
60. 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 Jun;95(6):594-603.[Abstract][Full Text]
61. Rondelli D, Goldberg JD, Isola L, et al. MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. Blood. 2014 Aug 14;124(7):1183-91.[Abstract][Full Text]
62. Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2010 Mar;16(3):358-67.[Abstract][Full Text]
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65. Hernández-Boluda JC, Pereira A, Kröger N, et al. Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: a study of the chronic malignancies working party of EBMT and the Spanish Myelofibrosis Registry. Am J Hematol. 2021 Oct 1;96(10):1186-94.[Abstract][Full Text]
66. Gagelmann N, Salit RB, Schroeder T, et al. High molecular and cytogenetic risk in myelofibrosis does not benefit from higher intensity conditioning before hematopoietic cell transplantation: an international collaborative analysis. Hemasphere. 2022 Oct;6(10):e784.[Abstract][Full Text]
67. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):799-807.[Abstract][Full Text]
68. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98.[Abstract][Full Text]
69. Cervantes F, Vannucchi AM, Kiladjian JJ, et al.; COMFORT-II investigators. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013 Dec 12;122(25):4047-53.[Abstract][Full Text]
70. Harrison CN, Mesa RA, Kiladjian JJ, et al. Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy. Br J Haematol. 2013 Jul;162(2):229-39.[Abstract]
71. Verstovsek S, Mesa RA, Gotlib J, et al. Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I. Haematologica. 2013 Dec;98(12):1865-71.[Abstract][Full Text]
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73. Pardanani A, Tefferi A, Masszi T, et al. Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis. Br J Haematol. 2021 Oct;195(2):244-8.[Abstract][Full Text]
74. Harrison CN, Mesa RA, Jamieson C, et al. Case series of potential Wernicke's encephalopathy in patients treated with fedratinib. Blood. 2017 Dec 8;130(1 suppl):4197.[Full Text]
75. Polverelli N, Mauff K, Kröger N, et al. Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: a retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT). Am J Hematol. 2021 Jan;96(1):69-79.[Abstract][Full Text]
76. Tefferi A, Mesa RA, Nagorney DM, et al. Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood. 2000 Apr 1;95(7):2226-33.[Abstract][Full Text]
77. Elliott MA, Chen MG, Silverstein MN, et al. Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia. Br J Haematol. 1998 Nov;103(2):505-11.[Abstract][Full Text]
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86. Shanavas M, Popat U, Michaelis LC, et al. Outcomes of allogeneic hematopoietic cell transplantation in patients with myelofibrosis with prior exposure to Janus kinase 1/2 inhibitors. Biol Blood Marrow Transplant. 2016 Mar;22(3):432-40.[Abstract][Full Text]
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