Myelofibrosis

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Myelofibrosis
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Myelofibrosis

• Clonal stem cell disease
• Increased number of hematopoietic and endothelial
  precursors
• Stromal proliferation is reactive due to
• increase in collagen, fibronectin, laminin and
  tenascin, caused by
• Increased levels of PGDF and TGF-beta and
• Decreased levels of MMP
• Osteosclerosis due to increased levels of OPG

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Diagnosis
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Risicostratificatie in MF
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Risicostratificatie in MF
Age Hb (g/dL) Karyotype Median survival n
lt65 lt 10 normal 54 7
abnormal 22 7
gt 10 normal 180 25
abnormal 72 11
gt65 lt 10 normal 44 13
abnormal 16 14
gt 10 normal 70 22
abnormal 78 7
Sheffield scoring system Reilly JT BJH 98
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Risicostratificatie in MF
Cervantes score all 55 years
Adverse prognostic factors
Hb lt 10 g/dL
Blood blasts 1
Comstitutional symptoms
Low risk 0-1 factor median survival 176 m
High risk 2-3 factors median survival 32 m
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Rol JAK-2 in risicostratificatie in MF?
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Treatment of myelofibrosis

• supportive care
• hematopoietic growth factors
• thalidomide
• splenectomy
• radiation
• allogeneic stemcell transplantation

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Androgens

• Nandrolone, fluoxymestrolone, oxymetholone,
  danazole
• Increase in marrow function in 40
• Especially in patients without cytogenetic
  abnormalities and splenomegaly
• Treat for at least 6 months
• Danazole also affects thrombocytopenia and
  splenomegaly

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Erythropoietin

• If serum EPO level is low
• 10000 U 3x/week, double after 1-2 months
• Discontinue treatment if response is lacking
  after 3-4 months
• Small series

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Thalidomide in MF
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Future medicines

• Bifosfanates
• Statins

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Splenectomy

• Indications
• Refractory hemolysis and/or thrombocytopenia
• Symptomatic splenomegaly
• Splenic infarction
• Severe portal hypertension

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Splenectomy

• Complications
• Bleeding
• Especially hemoperitoneum
• Infections
• Subfrenic abcess, pneumonia, sepsis
• Thrombosis
• Especially portal veins

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Splenectomy

• Complications
• Bleeding
• Especially hemoperitoneum
• Infections
• Subfrenic abcess, pneumonia, sepsis
• Thrombosis
• Especially portal veins

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Splenectomy

• Complications two single institutes
• Operative morbidity 39.3 and 31
• Mortality 8.4 and 9
• 3 month post splenectomy mortality 26
• Barosi 1993, Tefferi 2000

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Tefferi 2000
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Tefferi 2000
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Tefferi 2000
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Tefferi 2000
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Tefferi 2000
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Who benefits?
Tefferi 2000
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Who benefits?
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Who benefits?
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Long term complications

• Blast formation
• Cumulative incidence at 12 years 55 vs
  27 Barosi
• At 14 months 16.3 Tefferi
• no effect on survival 25.6 versus 23.9
  months Tefferi
• Hepatomegaly
• 16-24, some liverfailure
• Thrombocytosis
• 20-22, especially if platelet gt 50 presplenectomy

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Long term complications
Tefferi 2000
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Radiotherapy

• In patients unsuitable for surgery
• Symptomatic relief, with moederate reduction in
  spleen size, lasting for about 6 months
• Unpredictable cytopenias in a considerable number
  of patients
• Mortality 10-15

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Allogene Tx voor MF

• intermediair en hoog risico
• myeloablatief bij patienten lt50, tot 50 genezing
• allo RIST minder TRM, mogelijk hogere OS

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Allo-RIST