PVSG and WHO vs European Clinical, Molecular and Pathological Criteria for prefibrotic myeloproliferative neoplasms

Table 6 World Health Organization and European Clinical, Molecular and Pathological staging of prodromal, classical and advanced polycythemia vera related to therapy

PV, ECMP stage	0		1	2	3	4	5
Michiels ECMP Clinical diagnosis	Erythrocy-themic PV	Prodromal PV mimicking ET	Polycythemic PV prefibrotic	Classic PV prefibrotic	Advanced PV PMF stage	Post-PV MF Spent phase PV	Leukemic evolution MDS AL
LAP-score	N/↑	↑	↑	↑	↑/↑↑	Variable	Variable
Red cell mass	↑	N	↑	↑	↑	Variable	N/↓
Serum EPO	N/↓	N/↓	↓	↓	↓	Variable	N/↓
Leukocytes × 109/L	< 12	< 12	< 12	N-> 12	> 15	> 20	> 20
Platelets × 109/L	< 400	> 400	< 400	> 400	< or > 1000	Variable	Variable
Hemoglobin g/dL (mmol/L)	> 16 (10)	< 16 (10)	> 16 (10)	> 16 (10)	> 16 (10)	N/> 12	< 12
Hematocrit	> 0.51	< 0.51	> 0.51	> 0.51	> 0.51	Variable	N↓
Erythrocytes × 1012/L	> 6	< 6	> 6	> 6	> 6	Variable	N/↓
ECMP bone marrow	Early PV	Pro-PV	Early PV	Trilinear PV	Trilinear PV	Myelofibrosis	AML
Bone marrow cellularity (%) Grading myelofibrosis[57]	50-80 RF 0-1	50-80 RF 0-1	60-90 RF 0-1	80-100 RF 0/1, MF 0	80-100 RCF 2/3 MF 1/2	Decreased RCF 3/4 MF 2/3	Increased No MF
Splenomegaly on palpation	No	No/+	No/+	+	++/+++	/Large	Large
Spleen size, echogram cm	< 12	< 12-15	12-15	12-18	18-> 20	> 20	> 20
Spontaneous EEC+	+	+	+	+	+	+	No
JAK2V617F in granulocytes BFU-e (exon 12)	+	+	+	+/++	+/++	++	No or +
	+(++)	+(++)	+(++)	++	++	++	No
Therapeutic implications	Low risk	Low risk	Low risk	Intermediate risk PV	High risk PV	Post-PV MF Spent phase	Acute leukemia
First line treatment option[82,83] Asp/Phleb[82,83] IFN[84-86] MPN reductive treatment Hydroxyurea[83] JAK2 inhibitor[87-90]	Aspirin phlebotomy	Aspirin phlebotomy low dose IFN?	Phlebotomy Aspirin Low dose IFN → Complete response	Phlebotomy1 Aspirin IFN→ if resistant →HU	If IFN resistant→ HU or HU first line	JAK2 inhibitor→Bone marrow transplantation Aspirin?	Chemotherapy Bone marrow transplantation? Supportive

¹↑: Increased; ↓: Decreased; N: Normal; +: Present or heterozygous; ++: Homozygous. ET: Essential thrombocythemia; PV: Polycythemia vera; MPN: Myeloproliferative neoplasms; MF: Myelofibrosis; AMM: Agnogenic myeloid metaplasia; IFN: Interferon; EEC: Endogenous erythroid colony; ECMP: European Clinical, Molecular and Pathological; LAP: Leukocyte alkaline phosphatase; RCF: Reticulin/collagen fibrosis; RF: Reticulin fibrosis.