Myeloproliferative and thrombotic burden and treatment outcome of thrombocythemia and polycythemia patients

Table 6 Staging of JAK2^V617F positive prodromal polycythemia vera, erythrocythemic polycythemia vera, and five stages of PV according to WHO-ECMP criteria related to therapy anno 2014[10,13,34-37]

PV: WHO-ECMP stage	0	1	2	3	4	5	6
WHO-ECMP clinical diagnosis	Prodromal PV	Erythrocy-themic PV	Early PV	Overt PV Classical PV	PV PMF Masked PV	Post-PV MF Spent PV	Leukemic PV MDS/AL
LAP-score	↑	↑	↑	↑	↑/↑↑	Variable	Variable
Red cell mass	N	↑	↑	↑	↑	Variable	N/↓
Serum EPO	N/↓	N/↓	↓	↓	↓	Variable	N/↓
Erythrocytes × 1012/L	< 5.8	> 5.8	> 5.8	> 5.8	< 5.8	Variable	N/↓
Leukocytes × 109/L	< 12	< 12	< or > 12	< or- > 15	> 15	> 20	> 20
Platelets × 109/L	> 400	400	< or > 400	> 400	< or > 1000	Variable	Variable
WHO-ECMP bone marrow	Early PV	Early PV	Early PV	Trilinear PV	Trilinear PV	Myelofibrosis	Leukemic
Bone marrow cellularity (%)	50-80	50-80	60-100	80-100	80-100	Decreased	Increased
Grading reticulin fibrosis: RF	RF 0-1	RF 0-1	RF 0-1	RF 0/1,	RCF 2/3	RCF 3/4
Grading myelofibrosis: MF57	MF 0	MF 0	MF 0	MF 0	MF 1/2	MF 2/3
Splenomegaly on palpation	No/+	No	No/+	+	++/+++	/Large	Large
Spleen size, echogram cm	< 12-15	< 13	12-15	12-18	18 - > 20	> 20	> 20
Spleen size on palpation cm	0-3	NP	0-3	4-6	> 6	> 8	> 8
JAK2V617F in Granulocytes %	low	low	Moderate < 50	High > 50	High > 50	High > 50	No or ++
JAK2V617F in BFU-e (exon 12)	+(++)	+(++)	+(++)	++	++	++
Therapeutic implications	Low risk	Low risk	Low risk	Intermediate risk PV	High risk PV-MF	Post-PV MF Spent phase PV	Leukemia
Anno 2014
First line aspirin/Phlebotomy Second line IFN vs HU Third line JAK2 inhibitor	Aspirin Phlebotomy	Aspirin Phlebotomy	Phlebotomy Aspirin Low dose IFN → responsive	Phlebotomy1 Aspirin IFN à resistant → HU	If IFN resistant → HU or JAK2 inhibitor	JAK2 Inhibitor → Bone marrow transplantation	Chemotherapy Bone marrow transplantation? Supportive

¹↑: Increased; ↓: Decreased; N: Normal; +: Present or heterozygous; ++: Homozygous; HU: Hydroxyurea; PV: Polycythemia vera; MF: Myelofibrosis; WHO-ECMP: World Health Organization and European Cliical Molecular and Pathological; LAP: Leukocyte alkaline phosphatase; EPO: Erythropoietin.