Diagnosis

Approximately 30% of patients with MF are asymptomatic at diagnosis.1 MF is usually diagnosed after a routine physical examination reveals splenomegaly, anemia, leukocytosis, and/or thrombocytosis in the patient.1



Patients with suspected MF must undergo a careful clinical examination to rule out other possible causes of thrombocytosis or bone marrow fibrosis, including other MPNs.1

 

Diagnostic Criteria

The differential diagnosis of MF, as with other MPNs, is important because it guides patient management during follow-up and has an impact on prognosis.18 To aid diagnosis in clinical practice, the World Health Organization (WHO) has established the following diagnostic criteria for PMF, post-PV MF, and post-ET MF.1

 
 
 

Testing

A complete blood cell count (CBC) is usually obtained to evaluate the hemoglobin level, white blood cell count, and platelet count.19,20 A peripheral blood smear may also be obtained to look for the presence of leukoerythroblastosis to help with diagnosis.1,20

 

Evaluation of bone marrow histopathology is critical for proper diagnosis of MF. The bone marrow biopsy of a patient with MF typically reveals megakaryocyte proliferation and atypia, usually with reticulin or collagen fibrosis.1,21

 
 

The JAK2 V617F mutation is present in approximately 65% of patients with PMF and is considered a clonal marker of the disease.22 Thus, genetic testing is now often performed to distinguish PMF from other causes of bone marrow fibrosis.1

 
 

Emerging research indicates that mutations in the CALR gene may be present in most patients with MF without JAK2 or MPL mutations.23

 

 

 

References

  • Swerdlow SH, Campo E, Harrison NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Vol 2. 4th ed. Geneva: World Health Organization; 2008.
  • Abdel-Wahab OI, Levine RL. Primary myelofibrosis: Update on definition, pathogenesis, and treatment. Annu Rev Med. 2009;60:233-245.
  • Mesa RA, Schwager S, Radia D, et al. The myelofibrosis symptom assessment form (MFSAF): An evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res. 2009;33(9):1199-1203.
  • Girodon F, Bonicelli G, Schaeffer C, et al. Significant increase in the apparent incidence of essential thrombocythemia related to new WHO diagnostic criteria: A population-based study. Haematologica. 2009;94(6):865-869.
  • Hasselbalch HC. The role of cytokines in the initiation and progression of myelofibrosis. Cytokine Growth Factor Rev. 2013;24(2):133-145.
  • Levine RL, Pardanani A, Tefferi A, Gilliland DG. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer. 2007;7(9):673-683.
  • Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379-2390.
  • 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;113(13):2895-2901.
  • Tefferi A. Essential thrombocythemia, polycythemia vera, and myelofibrosis: Current management and the prospect of targeted therapy. Am J Hematol. 2008;83(6):491-497.
  • Cervantes F, Barosi G. Myelofibrosis with myeloid metaplasia: Diagnosis, prognostic factors, and staging. Semin Oncol. 2005;32(4):395-402.
  • Scherber R, Dueck AC, Johansson P, et al. The myeloproliferative neoplasm symptom assessment form (MPN-SAF): International prospective validation and reliability trial in 402 patients. Blood. 2011;118(2):401-408.
  • Barosi G. Myelofibrosis with myeloid metaplasia: Diagnostic definition and prognostic classification for clinical studies and treatment guidelines. J Clin Oncol. 1999;17(9):2954-2970.
  • O'Reilly RA. Splenomegaly at a united states county hospital: Diagnostic evaluation of 170 patients. Am J Med Sci. 1996;312(4):160-165.
  • Thiele J, Kvasnicka HM. Grade of bone marrow fibrosis is associated with relevant hematological findings-a clinicopathological study on 865 patients with chronic idiopathic myelofibrosis. Ann Hematol. 2006;85(4):226-232.
  • Tefferi A, Lasho TL, Jimma T, et al. One thousand patients with primary myelofibrosis: The mayo clinic experience. Mayo Clin Proc. 2012;87(1):25-33.
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  • Silver RT, Chow W, Orazi A, Arles SP, Goldsmith SJ. Evaluation of WHO criteria for diagnosis of polycythemia vera: A prospective analysis. Blood. 2013;122:1881-1886.
  • Tefferi A. How I treat myelofibrosis. Blood. 2011;117(13):3494-3504.
  • Mascarenhas JO, Orazi A, Bhalla KN, Champlin RE, Harrison C, Hoffman R. Advances in myelofibrosis: A clinical case approach. Haematologica. 2013;98(10):1499-1509.
  • Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the world health organization (WHO) classification of myeloid neoplasms and acute leukemia: Rationale and important changes. Blood. 2009;114(5):937-951.
  • Tefferi A. Mutations galore in myeloproliferative neoplasms: Would the real spartacus please stand up? Leukemia. 2011;25(7):1059-1063.
  • Abdel-Wahab O, Pardanani A, Bernard OA, et al. Unraveling the genetic underpinnings of myeloproliferative neoplasms and understanding their effect on disease course and response to therapy: Proceedings from the 6th international post-ASH symposium. Am J Hematol. 2012;87(5):562-568.
  • Rumi E, Pietra D, Guglielmelli P, et al. Acquired copy-neutral loss of heterozygosity of chromosome 1p as a molecular event associated with marrow fibrosis in MPL-mutated myeloproliferative neoplasms. Blood. 2013;121:4388-4395.
  • Rumi E, Pietra D, Pascutto C, et al. Clinical effect of driver mutations of JAK2, CALR or MPL in primary myelofibrosis. Blood. 2014; 124:1062-1069.
  • Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391-2405.
  • Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: A study by the IWG-MRT (international working group for myeloproliferative neoplasms research and treatment). Blood. 2010;115(9):1703-1708.
  • Vannucchi AM, Lasho TL, Guglielmelli P, et al. Mutations and prognosis in primary myelofibrosis. Leukemia. 2013;27:1861-1869.
  • Guglielmelli P, Lasho TL, Rotunno G, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: An international study of 797 patients. Leukemia. 2014;28:1804-1810.
  • Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: Clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472-1477.
  • Tefferi A, Guglielmelli P, Lasho TL, et al. CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: An international study of 570 patients. Leukemia. 2014;1494-1500.