Diagnostic Criteria for Primary Myelofibrosis (PMF)

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR or MPL mutation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression and shortened survival.

Diagnostic criteria for primary myelofibrosis

WHO criteria for prePMF

Major criteria
1. Megakaryocytic proliferation and atypia, without reticulin fibrosis .grade 1, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation, and often decreased erythropoiesis
2. Not meeting the WHO criteria for BCR-ABL1+, chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), myelodysplastic syndromes, or other myeloid neoplasms
3. Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal marker,† or absence of minor reactive BM reticulin fibrosis‡

Minor criteria
Presence of at least 1 of the following, confirmed in 2 consecutive determinations:
a. Anemia not attributed to a comorbid condition
b. Leukocytosis ≥11000/µL
c. Palpable splenomegaly
d. LDH increased to above upper normal limit of institutional reference range
Diagnosis of prePMF requires meeting all 3 major criteria, and at least 1 minor criterion

†In 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) are of help in determining the clonal nature of the disease.
‡Minor (grade 1) reticulin fibrosis secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukemia or other lymphoid neoplasm,
metastatic malignancy, or toxic (chronic) myelopathies.

WHO criteria for overt PMF

Major criteria
1. Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3
2. Not meeting WHO criteria for BCR-ABL1+, chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), myelodysplastic syndromes, or other myeloid neoplasms
3. Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal marker,† or absence of reactive myelofibrosis‡

Minor criteria
Presence of at least 1 of the following, confirmed in 2 consecutive determinations:
a. Anemia not attributed to a comorbid condition
b. Leukocytosis ≥11000/µL
c. Palpable splenomegaly
d. LDH increased to above upper normal limit of institutional reference range
e. Leukoerythroblastosis
Diagnosis of overt PMF requires meeting all 3 major criteria, and at least 1 minor criterion

†In 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) are of help in determining the clonal nature of the disease.
‡BM fibrosis secondary to infection, autoimmune disorder, or other chronic inflammatory conditions, hairy cell leukemia or other lymphoid neoplasm, metastatic malignancy, or toxic (chronic) myelopathies.

 

References:

  1. Barbui T, Thiele J, Gisslinger H, Kvasnicka HM, Vannucchi AM, Guglielmelli P, Orazi A, Tefferi A. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018 Feb 9;8(2):15. [Medline]
  2. Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016 Dec;91(12):1262-1271 [Medline]

 

Created: Mar 13, 2019.

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