The Chronic Myeloproliferative Disorders MPD

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The Chronic Myeloproliferative Disorders (MPD)

• John Matthews

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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

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1. Myeloproliferative disorders are clonal and
the fibrosis is reactive
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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
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Essential Thrombocythemia
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Normal Regulation of Platelet Numbers by
Thrombopoietin - TPO

• Constitutive production of thrombopoietin by
  liver
• Bound by platelets
• Excess stimulates megakaryopoiesis

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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

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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 M
onos 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
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Normal
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Essential Thrombocythemia
note giant platelets
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ET clinical features

• None
• Erythromelalgia
• Peripheral Vascular Occlusion
• Transient Ischemic Attack (TIA)
• Stroke
• Bleeding (esp surgical)

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ET differential diagnosis

• reactive thrombocytosis
• primary thrombocytosis
• ET
• PV, MF
• Chronic Myeloid Leukemia

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ET- treatment

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

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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.

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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

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PRV - clinical features

• Headaches
• Itch
• Vascular occlusion
• Venous thrombosis
• TIA, stroke, MI
• Splenomegaly

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PRV - diagnosis

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

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PRV differential diagnosis

• secondary polycythemia
• spurious polycythemia

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PRV - treatment

• phlebotomy to control hematocrit
• low-dose aspirin
• hydroxyurea if necessary
• avoid iron

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(Primary) Myelofibrosis (MF)

• neoplastic (clonal) hemopoietic stem cell
  disorder
• bone marrow failure
• myeloid metaplasia (extra-medullary hemopoiesis)

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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 B
asos x 109/L 0.1 0-0.1 Film Comment a few
nucleated red cells and myelocytes
(leukoerythroblastic). Tear-drop poikilocytes
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myelocyte
nucleated rbc
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Tear Drop Cells (or Tear Drop Poikilocytes)
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normal marrow trephine
cells
fat
bone
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myelofibrosis
fibrosis
new bone (arrows)
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MF - clinical

• Marrow failure
• splenomegaly

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MF - diagnosis

• typical blood picture
• splenomegaly
• dry aspirate
• fibrosis on trephine biopsy
• absence of other cause

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MF - treatment

• supportive care
• splenectomy or hydroxyurea if necessary
• consider allo-BMT