Table 2.

2016 World Health Organization diagnostic criteria for primary myelofibrosis

	Primary myelofibrosis (PMF) a
	Prefibrotic/early PMF (pre-PMF)	Overt PMF
Major criteria
1	Megakaryocytic proliferation and atypiab, without reticulin fibrosis > grade 1c, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation and often decreased erythropoiesis	Megakaryocyte proliferation and atypiab accompanied by either reticulin and/or collagen fibrosis (grade 2 or 3)
2	Not meeting WHO criteria for BCR-ABL1 + CML, PV, ET, MDS, or other myeloid neoplasm	Not meeting WHO criteria for BCR-ABL1 + CML, PV, ET, MDS or other myeloid neoplasm
3	Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal markerd or absence of minor reactive BM reticulin fibrosise	Presence of JAK2, CALR, or MPL mutation or in the absence, the presence of another clonal markerd or absence of evidence for reactive BM fibrosisf
Minor criteria
1	Presence of one or more of the following, confirmed in two consecutive determinations:	Presence of one or more of the following confirmed in two consecutive determinations:
	• Anemia not attributed to a comorbid condition	• Anemia not attributed to a comorbid condition
	• Leukocytosis ≥ 11 × 109/L	• Leukocytosis ≥ 11 × 109/L
	• Palpable splenomegaly	• Palpable splenomegaly
	• LDH level above the upper limit of the institutional reference range	• LDH level above the upper limit of the institutional reference range
		• Leukoerythroblastosis

Table adapted from Barbui T et al. Blood Cancer J. 2015; 5:e337¹⁰³. and Arber et al. Blood 2016;127:2391–2405²

BM, bone marrow; CML, chronic myeloid leukemia; MDS, myelodysplastic syndrome; LDH, serum lactate dehydrogenase

^aDiagnosis of prefibrotic/early PMF requires all three major criteria and at least one minor criterion. Diagnosis of overt PMF requires meeting all three major criteria and at least one minor criterion

^bSmall-to-large megakaryocytes with aberrant nuclear/cytoplasmic ratio and hyperchromatic and irregularly folded nuclei and dense clustering

^cIn cases with grade 1 reticulin fibrosis⁸⁷, the megakaryocyte changes must be accompanied by increased BM cellularity, granulocytic proliferation, and often decreased erythropoiesis (that is, pre-PMF)

^dIn the absence of any of the three major clonal mutations, the search for the most frequent accompanying mutations (ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1) are of help in determining the clonal nature of the disease

^eMinor (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

^fBM fibrosis secondary to infection, autoimmune disorder, or other chronic inflammatory conditions, hairy cell leukemia, or other lymphoid neoplasm, metastatic malignancy or toxic (chronic) myelopathies