European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms

Table 11 Staging of JAK2^V617F positive prodromal polycythemia vera, erythrocythemic polycythemia vera, classical polycythemia vera, early myelofibrosis, inapparent polycythemia vera, spent phase polycythemia vera and post-polycythemia vera myelofibrosis according to 2015 World Health Organization-Clinical Molecular and Pathological criteria related to therapy

PV: WHO-ECMP stage	0	1	2	3	4	5	6
WHO-ECMP	Prodromal	Erythrocy-themic PV	Early PV	Manifest PV	PV early MF	Inapparent	Spent PV
Clinical diagnosis	PV			Classical PV	Masked PV	PV	Post-PV MF
LAP-score	↑	↑	↑	↑	↑/↑↑	↑	Variable
EEC	+	+	+	+	+	+	+
Serum EPO	N/↓	N/↓	↓	↓	↓	↓	Variable
Erythrocytes × 1012/L	> 5.8	< 5.8	> 5.8	> 5.8	> 5.8	Normal < 5.5	Decreased
Leukocytes × 109/L	< 12	< 12	< or > 12	< or > 15	> 15	N or ↑	> 20
Platelets × 109/L	> 400	400	< or > 400	> 400	< or >1000	N low or ↑	Variable
WHO-ECMP bone marrow	Early PV	Early PV	Early PV	Trilinear PV	Trilinear PV	Prilinear PV	Myelofibrosis
Bone marrow cellularity (%)	50-80	50-80	60-100	80-100	80-100	60-100	Decreased
Grading reticulin fibrosis: RF	RF 0-1	RF 0-1	RF 0-1	RF 0/1	RCF1/2/3	RCF 1/2/3	RCF 3/4
Grading myelofibrosis: MF57	MF 0	MF 0	MF 0	MF 0	MF 0/1	MF 0/2	MF 2/3
Splenomegaly on palpation	No/+	No	No/+	+	++/+++	++/+++	/large
Spleen size, echogram (cm)	< 12-15	< 13	12-15	12-16	18 > 20	16 > 20	> 20
Spleen size on palpation (cm)	0-3	NP	0-3	4-6	> 6	> 6	> 8
JAK2V617F in granulocytes %	Low	Low	Moderate < 50	High > 50	High > 50	Mod/High	High > 50
JAK2V617F in BFU-e (exon 12)	+(++)	+(++)	+(++)	++	++	+	++
Risk stratification → therapeutic implications anno 2014	Low risk	Low risk	Low risk	Intermediate risk PV	High risk	Wait/see	Post-PV MF
					PV early MF	IFN	Spent phase PV
						JAK2
First line Aspirin/Phlebotomy	Aspirin	Aspirin	Phlebotomy	Phlebotomy	If IFN resistant →	If IFN	JAK2
Second line IFN vs HU	Phlebotomy	Phlebotomy	Aspirin	Aspirin	HU or JAK2	Resistent	Inhibitor →
Third line JAK2 inhibitor			Low dose IFN → responsive	IFN → resistant → HU	inhibitor	JAK2 inhibitor	Bone marrow transplant

↑: Increased; ↓: Decreased; N: Normal; +: Present or heterozygous; ++: Homozygous; MF: Myelofibrosis; EPO: Erythropoetin; PV: Polycythemia vera; WHO-ECMP: World Health Organization European Clinical Molecular and Pathological; RF: Reticulin fibrosis; LAP: Leukocyte alkaline phosphatase; EEC: Endogenous erythroid colony; BFU-e: Burst forming units erythropoiesis; RCF: Reticulin collagen fibrosis; IFN: Interferon; HU: Hydroxy urea.