The Chronic Myeloproliferative Disorders (MPD)

1. The Chronic Myeloproliferative Disorders (MPD) John Matthews

3. MPD - concepts • Neoplastic (clonal) disorders of hemopoietic stem cells • Over-production of all cell lines, with usually one line in particular • Fibrosis is a secondary event • Acute Myeloid Leukemia may occur

5. 1. Myeloproliferative disorders are clonal and the fibrosis is ‘reactive’

6. MPD - inclusions and nomenclature 1. Polycythemia (Rubra) Vera (PRV, PV) 2. Myelofibrosis (with Myeloid Metaplasia), Agnogenic Myeloid Metaplasia (MF,MMM, AMM) 3. Essential (Primary) Thrombocythemia

7. Essential Thrombocythemia

8. Normal Regulation of Platelet Numbers by Thrombopoietin - TPO • Constitutive production of thrombopoietin by liver • Bound by platelets • Excess stimulates megakaryopoiesis

10. Essential Thrombocythemia (ET) • Neoplastic stem cell disorder causing dysregulated production of large numbers of abnormal platelets • Some cases non-clonal (esp young women) • Abnormal platelets aggregate in vivo, causing thrombosis • Abnormal platelets also cause bleeding

11. ET-Typical Blood Count WBC x 109/L 10.0 [4-11] Hb g/L 156 [140-180] MCV fl 85 [80-100] Platelets x 109/L 1560 [150-450] Neuts x 109/L 7.0 [2-7.5] Lymphs x 109/L 2.0 [1.5-4] Monos x 109/L 0.8 [0.2-0.8] Eos x 109/L 0.1 [0-0.7] Basos x 109/L 0.1 [0-0.1] Film Comment: many large and abnormal platelets present

12. Normal

13. Essential Thrombocythemia note giant platelets

14. ET – clinical features • None • Erythromelalgia • Peripheral Vascular Occlusion • Transient Ischemic Attack (TIA) • Stroke • Bleeding (esp surgical)

15. ET – differential diagnosis • reactive thrombocytosis • primary thrombocytosis • ET • PV, MF • Chronic Myeloid Leukemia

16. ET- treatment • None in low-risk cases • Anti-platelet agents (aspirin) • Platelet reduction treatment

17. Polycythemia (Rubra) Vera (PV, PRV) A neoplastic stem cell disorder possessing a JAK-2 mutation, which leads to excessive production of all myeloid cell lines, but predominantly red cells. The increase in whole blood viscosity causes vascular occlusion and ischemia, compounded by the increase in platelets.

18. PRV - typical blood count WBC x 109/L 18.0 [4-11] Hb g/L 200 [140-180] HCt 0.62 [.42-.51] MCV fl 75 [80-100] Platelets x 109/L 850 [150-450] Neuts x 109/L 14.6 [2-7.5] Lymphs x 109/L 2.0 [1.5-4] Monos x 109/L 0.8 [0.2-0.8] Eos x 109/L 0.1 [0-0.7] Basos x 109/L 0.5 [0-0.1] Film: microcytosis: large and abnormal platelets present

19. PRV - clinical features • Headaches • Itch • Vascular occlusion • Venous thrombosis • TIA, stroke, MI • Splenomegaly

20. PRV - diagnosis • exclude secondary polycythemia • look for features of primary polycythemia • measure erythropoietin • JAK-2 mutation analysis

21. PRV – differential diagnosis • secondary polycythemia • spurious polycythemia

22. PRV - treatment • phlebotomy to control hematocrit • low-dose aspirin • hydroxyurea if necessary • avoid iron

23. (Primary) Myelofibrosis (MF) • neoplastic (clonal) hemopoietic stem cell disorder • bone marrow failure • myeloid metaplasia (extra-medullary hemopoiesis)

24. MF - typical blood count WBC x 109/L 2.4 [4-11] Hb g/L 88 [140-180] MCV fl 85 [80-100] Platelets x 109/L 60 [150-450] Neuts x 109/L 1.0 [2-7.5] Lymphs x 109/L 1.0 [1.5-4] Monos x 109/L 0.2 [0.2-0.8] Eos x 109/L 0.1 [0-0.7] Basos x 109/L 0.1 [0-0.1] Film Comment: a few nucleated red cells and myelocytes (leukoerythroblastic). Tear-drop poikilocytes

25. myelocyte nucleated rbc

26. Tear Drop Cells (or Tear Drop Poikilocytes)

27. normal marrow trephine cells fat bone

28. myelofibrosis fibrosis new bone (arrows)

29. MF - clinical • Marrow failure • splenomegaly

30. MF - diagnosis • typical blood picture • splenomegaly • dry aspirate • fibrosis on trephine biopsy • absence of other cause

31. MF - treatment • supportive care • splenectomy or hydroxyurea if necessary • consider allo-BMT