MYELOFIBROSIS RISK
MYELOFIBROSIS RISK
 

Myelofibrosis (MF) is a rare, progressive, myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, and anemia.1,2

This tool is designed to help evaluate a patient for MF. For patients who have been diagnosed with MF, it helps estimate prognosis based on validated models.

Choose a topic or tool below.

 
 

Identification and characterization of patients with myelofibrosis (MF)

 

Key characteristics of MF

  • MF is a serious hematologic malignancy characterized by multiple genetic, epigenetic, and cellular alterations3-5
  • Diagnosis is made with a combination of laboratory analyses and clinical patient evaluation6
  • Overactive JAK signaling is a key underlying driver of the disease7-9

MF can develop de novo or from progression of PV (Post–PV MF) or ET (Post–ET MF)10,11

BCR-ABL1 = breakpoint cluster region-Abelson leukemia virus oncoprotein 1; CML = chronic myelogenous leukemia; ET = essential thrombocythemia; MF = myelofibrosis; MPNs = myeloproliferative neoplasms; PV = polycythemia vera.

aOther diseases are also classified as MPNs by the World Health Organization (WHO). These include chronic neutrophilic leukemia; chronic eosinophilic leukemia, not otherwise specified; and MPN, unclassifiable.6

MF IDENTIFICATION & RISK TOOL

Select a criterion below to begin

Identification of Primary Myelofibrosis (PMF)

This tool helps evaluate whether a patient’s profile is consistent with a diagnosis of PMF based on World Health Organization (WHO) guidelines. Diagnosis requires meeting all 3 major criteria and at least 1 minor criterion (confirmed in 2 consecutive determinations).6

Check the criteria corresponding to the patient’s clinical presentation.

MAJOR CRITERIA

Proliferation and atypia of megakaryocytes accompanied by either reticulin and/or collagen fibrosis grades 2 or 3 on a scale of 0 to 3 

Not meeting WHO criteria for ET, PV, BCR-ABL1+ CML, myelodysplastic syndromes, or other myeloid neoplasms

Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal markera or absence of reactive myelofibrosisb

MINOR CRITERIA

Anemia not attributed to a comorbid condition
Leukocytosis ≥11 x 109/L
Palpable splenomegaly
LDH increased to above upper normal limit of institutional reference range
Leukoerythroblastosis
 

CALR = calreticulin; CML = chronic myelogenous leukemia; JAK = Janus-associated kinase; LDH = lactate dehydrogenase; MPL = myeloproliferative leukemia virus oncogene.
aIn the absence of any of the 3 major clonal mutations, the search for the most frequent accompanying mutations (eg, ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1) is of help in determining the clonal nature of the disease.
bBone marrow fibrosis secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukemia or other lymphoid neoplasm, metastatic malignancy, or toxic (chronic) myelopathies.

  1. The Merck Manual for Health Care Professionals. Available at: http://www.merckmanuals.com/professional/hematology_and_oncology/myeloproliferative_disorders/primary_myelofibrosis.html?qt=myelofibrosis&alt=sh. Accessed June 23, 2014.
  2. Data on File, Incyte Corporation. Wilmington, DE.
  3. Lichtman MA, Tefferi A. Chapter 91. Primary Myelofibrosis. In: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, eds. Williams Hematology. 8th ed. New York: McGraw-Hill; 2011.
  4. Cervantes F, Dupriez B, Pereira A, et al. Blood. 2009;113:2895-2901.
  5. Vainchenker W, Delhommeau F, Constantinescu SN, et al. Blood. 2011;118:1723-1735.
  6. 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; 127(20):2391-2405.
  7. Verstovsek S, Kantarjian H, Mesa RA, et al. N Engl J Med. 2010;363:1117-1127.
  8. Santos FPS, Verstovsek S. Hematol Oncol Clin North Am. 2012;26:1083-1099.
  9. Fourouclas N, Li J, Gilby DC, et al. Haematologica. 2008;93:1635-1644.
  10. Vannucchi A, Guglielmelli P, Tefferi A. CA Cancer J Clin. 2009;59:171-191.
  11. Tefferi A. Am J Hematol. 2013:88:437-445.
  12. Barosi G, Mesa RA, Thiele J, et al; International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Leukemia. 2008;22:437-438.
  13. Passamonti F, Cervantes F, Vannucchi AM, et al. Blood. 2010;115:1703-1708.
  14. Gangat N, Caramazza D, Vaidya R, et al. J Clin Oncol. 2011;29:392-397.

Identification of Patients with Post–PV MF and Post–ET MF

This tool helps evaluate whether a patient’s profile is consistent with a diagnosis of post–polycythemia vera (PV) MF or post–essential thrombocythemia (ET) MF, according to the International Working Group for Myeloproliferative Neoplasms (IWG-MRT) guidelines.12

Check the criteria corresponding to the patient’s clinical presentation.

Patient History

Previous diagnosis of WHO-defined PV

Previous diagnosis of WHO-defined ET

Clinical Examination

Increasing splenomegaly
Constitutional symptoms 

Bone Marrow Biopsy

Bone marrow fibrosis 

Other Lab Results

Anemia 
Increased serum lactate dehydrogenase (LDH) 

Leukoerythroblastosis

 

  1. The Merck Manual for Health Care Professionals. Available at: http://www.merckmanuals.com/professional/hematology_and_oncology/myeloproliferative_disorders/primary_myelofibrosis.html?qt=myelofibrosis&alt=sh. Accessed June 23, 2014.
  2. Data on File, Incyte Corporation. Wilmington, DE.
  3. Lichtman MA, Tefferi A. Chapter 91. Primary Myelofibrosis. In: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, eds. Williams Hematology. 8th ed. New York: McGraw-Hill; 2011.
  4. Cervantes F, Dupriez B, Pereira A, et al. Blood. 2009;113:2895-2901.
  5. Vainchenker W, Delhommeau F, Constantinescu SN, et al. Blood. 2011;118:1723-1735.
  6. 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; 127(20):2391-2405.
  7. Verstovsek S, Kantarjian H, Mesa RA, et al. N Engl J Med. 2010;363:1117-1127.
  8. Santos FPS, Verstovsek S. Hematol Oncol Clin North Am. 2012;26:1083-1099.
  9. Fourouclas N, Li J, Gilby DC, et al. Haematologica. 2008;93:1635-1644.
  10. Vannucchi A, Guglielmelli P, Tefferi A. CA Cancer J Clin. 2009;59:171-191.
  11. Tefferi A. Am J Hematol. 2013:88:437-445.
  12. Barosi G, Mesa RA, Thiele J, et al; International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Leukemia. 2008;22:437-438.
  13. Passamonti F, Cervantes F, Vannucchi AM, et al. Blood. 2010;115:1703-1708.
  14. Gangat N, Caramazza D, Vaidya R, et al. J Clin Oncol. 2011;29:392-397.

Estimating Prognosis in Myelofibrosis (MF)

Prognostic criteria

Determining prognosis can be challenging because myelofibrosis has a very heterogeneous presentation. As the clinical understanding of myelofibrosis has evolved, a variety of prognostic systems have been developed.4

The International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) developed the International Prognostic Scoring System (IPSS) and the Dynamic International Prognostic Scoring System (DIPSS).4,13

Both IPSS and DIPSS use the same risk factors when estimating prognosis, but they differ in how the risk factors are weighted.4,13 DIPSS Plus is based on DIPSS and includes additional risk factors such as karyotype, transfusion dependency, and platelet count less than 100.14 Indicate which prognostic system you would like to use and check the criteria corresponding to the patient’s clinical presentation.


Patient History

Age 65 or above

Constitutional symptoms 

Lab Results

Hemoglobin level <10 g/dL

Leukocyte count >25 x 109/L

Circulating blast cells ≥1%

  1. The Merck Manual for Health Care Professionals. Available at: http://www.merckmanuals.com/professional/hematology_and_oncology/myeloproliferative_disorders/primary_myelofibrosis.html?qt=myelofibrosis&alt=sh. Accessed June 23, 2014.
  2. Data on File, Incyte Corporation. Wilmington, DE.
  3. Lichtman MA, Tefferi A. Chapter 91. Primary Myelofibrosis. In: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, eds. Williams Hematology. 8th ed. New York: McGraw-Hill; 2011.
  4. Cervantes F, Dupriez B, Pereira A, et al. Blood. 2009;113:2895-2901.
  5. Vainchenker W, Delhommeau F, Constantinescu SN, et al. Blood. 2011;118:1723-1735.
  6. 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; 127(20):2391-2405.
  7. Verstovsek S, Kantarjian H, Mesa RA, et al. N Engl J Med. 2010;363:1117-1127.
  8. Santos FPS, Verstovsek S. Hematol Oncol Clin North Am. 2012;26:1083-1099.
  9. Fourouclas N, Li J, Gilby DC, et al. Haematologica. 2008;93:1635-1644.
  10. Vannucchi A, Guglielmelli P, Tefferi A. CA Cancer J Clin. 2009;59:171-191.
  11. Tefferi A. Am J Hematol. 2013:88:437-445.
  12. Barosi G, Mesa RA, Thiele J, et al; International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Leukemia. 2008;22:437-438.
  13. Passamonti F, Cervantes F, Vannucchi AM, et al. Blood. 2010;115:1703-1708.
  14. Gangat N, Caramazza D, Vaidya R, et al. J Clin Oncol. 2011;29:392-397.

Patient History

Age 65 or above

Constitutional symptoms 

Other Lab Results

Hemoglobin level <10 g/dL

Leukocyte count >25 x 109/L

Circulating blast cells ≥1%

  1. The Merck Manual for Health Care Professionals. Available at: http://www.merckmanuals.com/professional/hematology_and_oncology/myeloproliferative_disorders/primary_myelofibrosis.html?qt=myelofibrosis&alt=sh. Accessed June 23, 2014.
  2. Data on File, Incyte Corporation. Wilmington, DE.
  3. Lichtman MA, Tefferi A. Chapter 91. Primary Myelofibrosis. In: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, eds. Williams Hematology. 8th ed. New York: McGraw-Hill; 2011.
  4. Cervantes F, Dupriez B, Pereira A, et al. Blood. 2009;113:2895-2901.
  5. Vainchenker W, Delhommeau F, Constantinescu SN, et al. Blood. 2011;118:1723-1735.
  6. 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; 127(20):2391-2405.
  7. Verstovsek S, Kantarjian H, Mesa RA, et al. N Engl J Med. 2010;363:1117-1127.
  8. Santos FPS, Verstovsek S. Hematol Oncol Clin North Am. 2012;26:1083-1099.
  9. Fourouclas N, Li J, Gilby DC, et al. Haematologica. 2008;93:1635-1644.
  10. Vannucchi A, Guglielmelli P, Tefferi A. CA Cancer J Clin. 2009;59:171-191.
  11. Tefferi A. Am J Hematol. 2013:88:437-445.
  12. Barosi G, Mesa RA, Thiele J, et al; International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Leukemia. 2008;22:437-438.
  13. Passamonti F, Cervantes F, Vannucchi AM, et al. Blood. 2010;115:1703-1708.
  14. Gangat N, Caramazza D, Vaidya R, et al. J Clin Oncol. 2011;29:392-397.

Patient History

Age 65 or above

Constitutional symptoms 

Other Lab Results

Hemoglobin level <10 g/dL

Leukocyte count >25 x 109/L

Circulating blast cells ≥1%

Platelets <100 x 109/L

KARYOTYPE

Unfavorable karyotype 

TRANSFUSION NEED

Red cell transfusion dependent

  1. The Merck Manual for Health Care Professionals. Available at: http://www.merckmanuals.com/professional/hematology_and_oncology/myeloproliferative_disorders/primary_myelofibrosis.html?qt=myelofibrosis&alt=sh. Accessed June 23, 2014.
  2. Data on File, Incyte Corporation. Wilmington, DE.
  3. Lichtman MA, Tefferi A. Chapter 91. Primary Myelofibrosis. In: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, eds. Williams Hematology. 8th ed. New York: McGraw-Hill; 2011.
  4. Cervantes F, Dupriez B, Pereira A, et al. Blood. 2009;113:2895-2901.
  5. Vainchenker W, Delhommeau F, Constantinescu SN, et al. Blood. 2011;118:1723-1735.
  6. 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; 127(20):2391-2405.
  7. Verstovsek S, Kantarjian H, Mesa RA, et al. N Engl J Med. 2010;363:1117-1127.
  8. Santos FPS, Verstovsek S. Hematol Oncol Clin North Am. 2012;26:1083-1099.
  9. Fourouclas N, Li J, Gilby DC, et al. Haematologica. 2008;93:1635-1644.
  10. Vannucchi A, Guglielmelli P, Tefferi A. CA Cancer J Clin. 2009;59:171-191.
  11. Tefferi A. Am J Hematol. 2013:88:437-445.
  12. Barosi G, Mesa RA, Thiele J, et al; International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Leukemia. 2008;22:437-438.
  13. Passamonti F, Cervantes F, Vannucchi AM, et al. Blood. 2010;115:1703-1708.
  14. Gangat N, Caramazza D, Vaidya R, et al. J Clin Oncol. 2011;29:392-397.
 

  1. The Merck Manual for Health Care Professionals. Available at: http://www.merckmanuals.com/professional/hematology_and_oncology/myeloproliferative_disorders/primary_myelofibrosis.html?qt=myelofibrosis&alt=sh. Accessed June 23, 2014.
  2. Data on File, Incyte Corporation. Wilmington, DE.
  3. Lichtman MA, Tefferi A. Chapter 91. Primary Myelofibrosis. In: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, eds. Williams Hematology. 8th ed. New York: McGraw-Hill; 2011.
  4. Cervantes F, Dupriez B, Pereira A, et al. Blood. 2009;113:2895-2901.
  5. Vainchenker W, Delhommeau F, Constantinescu SN, et al. Blood. 2011;118:1723-1735.
  6. 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; 127(20):2391-2405.
  7. Verstovsek S, Kantarjian H, Mesa RA, et al. N Engl J Med. 2010;363:1117-1127.
  8. Santos FPS, Verstovsek S. Hematol Oncol Clin North Am. 2012;26:1083-1099.
  9. Fourouclas N, Li J, Gilby DC, et al. Haematologica. 2008;93:1635-1644.
  10. Vannucchi A, Guglielmelli P, Tefferi A. CA Cancer J Clin. 2009;59:171-191.
  11. Tefferi A. Am J Hematol. 2013:88:437-445.
  12. Barosi G, Mesa RA, Thiele J, et al; International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Leukemia. 2008;22:437-438.
  13. Passamonti F, Cervantes F, Vannucchi AM, et al. Blood. 2010;115:1703-1708.
  14. Gangat N, Caramazza D, Vaidya R, et al. J Clin Oncol. 2011;29:392-397.