Dr. Sormann Siegfried

primäre Myelofibrose

PMF (agnogenic myeloid metaplasia, chronic idiopathic myelofibrosis) is characterized by the presence of bone marrow fibrosis that cannot be attributed to another myeloid disorder.
morphological phenotype of PMF can exist without the presence of overt bone marrow fibrosis - prefibrotic PMF


PMF – 60 to 65 percent JAK2 mutation, 20 to 25 percent CALR mutation, 7 percent MPL mutation; 8 to 10 percent triple negativ.
häufig: PMF harbor homozygous JAK2 mutations






Corticosteroids, erythropoietin, and danazol are used, with transient improvements in 20% to 40%

lenalidomide is recommended only in the presence of 5q abnormality

The JAK1/JAK2 inhibitor ruxolitinib was evaluated in the COMFORT-I and COMFORT-II studies, delivering meaningful results for spleen volume reduction and improvement in symptoms and quality oflife Dose-limiting myelosuppression,particularly in the first 3 months of therapy,wascommon.Increased risk for infection has been documented,ranging from common bacterial/viral ailments to rare severe infections such as progressive multifocal leukoencepha improvements in clinical status, for example, reversal of cachexia and control of systemic inflammation, are potential reasons. Long-term therapy may halt bone marrow fibrosis, and gradual decreases in mutant allele burden are seen Available data support the use of ruxolitinib in selected patients with intermediate-1-risk disease




The inclusion of spleen size in future prognostic scores is suggested bytheresults of the COMFORT trials,whichidentifiedlarger baseline spleen volume to associate with an increased risk for death

In the future, refinement of IPSS scores is likely, as disease with a CALR mutation, especially type 1/type 1-like,19-21 is associated with longer survival than JAK2, MPL, and so-called triple-negative disease. The high-molecular-risk category has been defined by the presence of a mutation in ASXL1, EZH2, SRSF2, IDH1, orIDH2.23 Prognosis is also informed by specific cytogenetic abnormalities